excellence DEFINED UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE School of Medicine

excellence DEFINED UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE

School of Medicine

University of Pittsburgh School of Medicine

1 Letter from the Dean

4 Why Pittsburgh?

16 News & Achievements

32 Education A M E S SAG E F R O M T H E D E A N

68 Research

102 Clinical Care

Y

ou probably know excellence when you see it,

or realize when you don’t, but what exactly is it?

127 Development

157 Departments

Even more to the point, how can excellence be

defined in terms of educating tomorrow’s physicians

and investigating today’s diseases? At the University of Pittsburgh School of Medicine, where excellence is an everyday pursuit (and a goal that is often attained), I believe that creativity and leadership are two of the characteristics of excellence that define it best. Why? Our mission, first and foremost, is to educate the finest clinicians and investigators, and to be successful in either—or, in some cases, both—of these ventures requires nothing less than outstanding creativity and leadership. One needs to be creative as a clinician because, despite all of the advances we have made in medicine, it is still quite often a mystery; and diagnoses are not always obvious. One needs to be creative as an

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investigator because research, by its very nature, involves a quest for that which is hidden and, if discovered, constitutes one more bit of the vast, intricate puzzle we call life. Furthermore, one needs leadership skills if one hopes to address the extremely complicated problems that we face in the delivery and financing of our nation’s health care. Clearly, on this matter in particular, not to

10987654321 Gauging Success by the Ultimate Metric

be part of the solution is to be part of the problem, which makes good leadership skills all the more essential. You can be certain that anyone accepted to medical school at the University of Pittsburgh will be exceptionally bright and accomplished. That’s a given. However, creativity and leadership are the qualities that we seek most in prospective students. In fact, I also highly value these attributes in our faculty, our administrators, and everyone else who has a hand in making our medical school what it is today. As evidence of our success in fostering creativity and leadership throughout nearly every facet of our operation, I’m delighted to share with you this latest progress report from the University of Pittsburgh School of Medicine. I believe it reflects just some of the many ways in which these qualities have become ingrained in the culture of this institution and have come to define its excellence. ARTHUR S. LEVINE, M.D. Senior Vice Chancellor for the Health Sciences and Dean, School of Medicine Summer 2007

Amid life’s countless measures of success (or at least the 252 million Google hits on the phrase “top 10”), for research-intensive academic health centers, the ultimate metric is funding by the National Institutes of Health. Unlike reputational rankings, the NIH process is the only objective, nationally competitive, peer-reviewed standard available for measuring their multi-mission success. According to this criterion, the University of Pittsburgh, driven mainly by the School of Medicine and its affiliates, has achieved a notable level of success not only by moving into the top 10 list of NIH funding recipients in 1997 but also by maintaining its position ever since —and steadily climbing within this enviable echelon as high as No. 7 among educational institutions and affiliates. Such ranking shifts are rare. Although more than 3,400 U.S. institutions, including nearly all of the nation’s 126 accredited medical schools, vie for NIH dollars, the competition is fierce (perhaps now more than ever with the stagnation in federal appropriations to NIH). Furthermore, those in the top 10 tend to receive and retain a disproportionately large share of the funding awards each year because in biomedical research — as in the rest of life — success breeds success. Case in point: Pitt and its medical school have both more than doubled their NIH support since 1998. However, to focus on this aspect of our performance to the exclusion of the others is unfair. There’s no such thing as a school that is strong in NIH support for its research program that doesn’t also have strength in its faculty, its clinical care program, and its students. They all go together, and, at the University of Pittsburgh, that composite is the true measure of our success.

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WHY PITTSBURGH?

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Why, indeed. We posed the question to some of the many people who recently made the move to the School of Medicine from other places. Here’s what they had to say.

Why Pittsburgh?

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Dr. Steve Shapiro in a favorite (but infrequent) nonwork setting

When Steven D. Shapiro, M.D., the new chair of medicine, informed his colleagues at Harvard Medical School that he was leaving for Pittsburgh, some of them said it seemed like a good idea, but others, like Jeffrey Drazen, M.D., editorin-chief of the New England Journal of Medicine, asked why he would do such a thing. “Well,” Shapiro says, “I actually got a call from him recently basically saying what a good decision I’d made.” Not only does Shapiro agree (“It’s everything I expected — and more,” he says), but he, too, admits to being somewhat surprised — not that the move has worked out so well but that he made the move at all, leaving Harvard as the Parker B. Francis Professor of Medicine and chief of Pulmonary and Critical Care Medicine at Boston’s Brigham and Women’s Hospital. So, what was it that got his attention? In a word: opportunity. “Right now, we’re on the verge of understanding disease processes like never before and transforming that understanding into therapies that will improve patient outcomes. I think that going to a place that has the vision, the resources, and the

critical mass to do that is what’s really appealing.” The more he looked at Pitt, the more he realized it offered him the best chance to make a difference. “I see Harvard as the present, but this place is the future,” Shapiro says. Now that he’s settling into his new role as head of the School of Medicine’s largest and most far-reaching department and as the Jack D. Myers Professor, he relishes the collaboration that he’s found among his new colleagues and their influence on his own acclaimed research, which has broadened in recent years from understanding the pathogenesis of chronic obstructive pulmonary disease and determining the proteinases responsible for lung destruction in emphysema to include the biological functions of those proteinases in lung cancer and infectious diseases. “I knew that people would be collaborative, but the quality of what they have to offer really makes my science stronger. It’s pretty amazing,” he says. “Of course, my own research is secondary to that of my faculty at this point, and I anticipate great things from them.”

“I see Harvard as the present, but STEVEN D. SHAPIRO, M.D.

this place is the future.”

WHY PITTSBURGH?

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J. TIMOTHY GREENAMYRE, M.D., PH.D.

“There’s a certain energy

level here that’s really exciting.” In an office well above the constant caravan of cars inching through Pitt’s campus, J. Timothy Greenamyre, M.D., Ph.D., has found his niche. When he first joined the Department of Neurology as professor and chief of the Movement Disorders Division, he says, “I had a little office where I had to climb over boxes to get to my desk, and I had a lab about the same size.” In the last year, he has seen both his office and lab space grow and the Pittsburgh Institute for Neurodegenerative Diseases (PIND) come to life. The opportunity to direct PIND was one of the key reasons Greenamyre came to Pittsburgh (finding true love once he got here was an unexpected bonus), and he has assembled a dozen

FA D I G . L A K K I S , M . D .

“It’s clear that Pittsburgh is committed to providing the resources and intellectual freedom that are needed to produce high-quality science. That’s why I’m here.” As an associate professor of medicine and immunology at Yale School of Medicine, Fadi G. Lakkis, M.D., found that his research on the roles of memory T cells and cytokines in allograft acceptance was rapidly distinguishing him as a leading thinker in the area of transplantation tolerance. However, when he was offered the opportunity to come to Pittsburgh as scientific director of the Thomas E. Starzl Transplantation Institute, he didn’t hesitate. “Everyone knows this is a good place,” says Lakkis, who also serves

as professor of surgery and immunology as well as the Frank and Athena Sarris Professor of Transplantation Biology. “It has already achieved great things. But more importantly, I get the impression that, no matter how much success there is here, there will always be a greater vision, a drive to do even better. It’s clear that Pittsburgh is committed to providing the resources and intellectual freedom that are needed to produce high-quality science. That’s why I’m here.”

scientists from the Departments of Neurology, Structural Biology, and Pharmacology and the Division of Geriatric Medicine to join him in the institute’s work. In BST3, the University’s newest research building where PIND is based, research areas are without walls delineating each lab’s space, and Greenamyre, who holds the UPMC Chair in Movement Disorders in Neurology, likes that layout. Being able to see, literally, fellow researchers fosters collaboration, he says. “There’s a certain energy level here that’s really exciting.” The decision to leave Emory University after 10 years was an easy one, he says. “There were all the markings of putting together something great here.”

BRUCE FREEMAN, PH.D.

“People in leadership roles at Pitt display a clear-cut vision of the future and an exquisite taste in science in terms of being able to identify what’s hot and what might be a little mundane or old hat.” “The vitality that comes from the adjustments and new learning that a move induces have been wonderful,” says Bruce Freeman, Ph.D., who, after 20 years, left the University of Alabama, Birmingham, as vice chair for research in anesthesiology to become UPMC Irwin Fridovich Professor and chair of pharmacology at Pitt. Part of the enticement was the kind of science being done here. “People in leadership roles at Pitt display a clear-cut vision of the future and an exquisite taste in science in terms of being able to identify what’s hot and what might be a little mundane or old hat,” he says. “There’s a nice synergy between my interests in inflammatory

mechanisms — and how to control them — with both basic science and clinical activities at Pitt; here, there’s a significant interest in how we can ‘harness’ inflammation to improve diseases related to aging (heart, joint, neurodegenerative disorders) and organ transplantation, and my work meshes nicely with those endeavors.” Other influences were less tangible. “It was just that amorphous spirit that you sense with people here,” he says. “There are indefinable energies that you see in a place where things are working well; people display optimism and a high level of energy, and those traits can’t help but also promote additional creativity.”

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ANGELA M. GRONENBORN, PH.D.

“I can interact with so many different types of people now. I can talk to clinicians and see firsthand how basic science supports and influences clinical care.”

Angela Gronenborn, Ph.D., has achieved one of the highest honors to which an American scientist can aspire. She is one of the 72 newest members of the prestigious National Academy of Sciences, all of whom were elected in recognition of distinguished and continuing achievements in original research. Pitt is now home to four of the academy’s 2,025 active members.

“Pittsburgh? Oh, it was all Art’s doing,” says Angela M. Gronenborn, Ph.D., who had achieved what most researchers only dream about — a tenured berth at the National Institutes of Health. Since NIH scientists aren’t obligated to look for funding or teach, Gronenborn was able to focus completely on her role as chief of the Structural Biology Section in the Laboratory of Chemical Physics at the National Institute of Diabetes and Digestive and Kidney Diseases. Along with most of her colleagues, she assumed it would be a lifelong position; a common joke was that anyone in his or her right mind would only leave the Bethesda campus feet first. “Leaving,” says Gronenborn, “is certainly not regarded as normal. People there were genuinely shocked. It takes someone either very crazy or very adventurous to do such a thing, and I’m not sure which category they thought I was in.” However, she knew someone who’d made a similar move: Arthur S. Levine, M.D., a former colleague who’s now senior vice chancellor for the health sciences and dean of the School

of Medicine. After leaving NIH in 1998, Levine stayed in contact with Gronenborn. “We talked about building things here,” she says. He was particularly interested in her input on plans for the new Biomedical Science Tower, BST3. Gronenborn freely offered her opinions on the concepts behind the building and how they might be executed. She thought she was simply taking part in an invigorating discussion about basic research in medical education. Art Levine had a better idea. “I wasn’t planning on going anywhere,” she says, “but he made me an offer I couldn’t refuse.” That offer was the chance to create and chair the new Department of Structural Biology. Now, as the UPMC Rosalind Franklin Professor, Gronenborn is based in the very building she helped plan. “I can interact with so many different types of people now,” she says. “I can talk to clinicians and see firsthand how basic science supports and influences clinical care. I have graduate students to keep me on my toes. There is a wonderful energy here.”

Dr. Angela Gronenborn at Pittsburgh’s Carnegie Museum of Art

WHY PITTSBURGH?

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GEORGE K. GITTES, M.D.

“The academic environment here was the strongest and had the greatest potential for me. I’m surrounded by colleagues who operate at a very high level.” When George K. Gittes, M.D., was considering his most recent career move, he had several opportunities before him — five to be exact. Universities across the country, including Pitt, wanted to hire him as chief of pediatric surgery. Pittsburgh won out, and Gittes is now surgeon-in-chief and director of pediatric surgical research at Children’s Hospital of Pittsburgh of UPMC as well as the Benjamin R. Fisher Professor

of Pediatric Surgery and professor of surgery at the School of Medicine. “The academic environment here was the strongest and had the greatest potential for me. I’m surrounded by colleagues who operate at a very high level, and I have the ability to recruit and develop top-notch faculty,” says Gittes. “It was clear to me that Pitt, by far, was the best choice.”

H A N S - C H R I S T O P H PA P E , M . D .

“This is one of the top orthopaedic In many ways, says HansChristoph Pape, M.D., Pittsburgh reminds him of Hannover, the German city from which he moved to become associate professor and chief of orthopaedic trauma surgery in the Department of Orthopaedic Surgery. “The cities are about the same size, you don’t have to spend hours in the car commuting, and there are many cultural options,” he says. “I’ve found the environment to be excellent.” Pape is known for his expertise in damage control orthopaedics, an approach adopted by trauma centers

around the world in which a critically injured patient’s major organs and systems are stabilized before orthopaedic repairs are made. The reaction of colleagues at Hannover Medical School to his departure ran the gamut. “Some were proud of me, some thought I was crazy, and some were even a little jealous,” Pape says. He thinks it was a great move. “The research opportunities here are excellent. This is one of the top orthopaedic centers in the world, and every graduate should be proud to have trained here.”

centers in the world.” MARY PHILLIPS, M.B.B.CH.

“There’s a terrific science community, from researchers to clinicians, at all levels, and I’m able to collaborate with so many people.” “Pittsburgh is second to none in neuroimaging and mood disorders,” says Mary Phillips, M.B.B.Ch. “It was a huge opportunity to come here and do this unique kind of research.” As professor of psychiatry and director of functional neuroimaging in emotional disorders, Phillips uses functional magnetic resonance imaging to examine the brain as a basis of emotion and the extent to

which neural mechanisms underlying emotions are normal in people with mood and anxiety disorders. She is pleased with how well her research is going since coming to Pitt from London’s Institute of Psychiatry. “There’s a terrific science community, from researchers to clinicians, at all levels, and I’m able to collaborate with so many people,” she says.

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G E R A L D F. G E B H A R T, P H . D .

“It was clear there were resources and opportunities here that are available at few other institutions.” Leading the School of Medicine’s new Pittsburgh Center for Pain Research (PCPR) is a leading expert in the subject, Gerald F. Gebhart, Ph.D., who left the University of Iowa’s College of Medicine as professor and head of pharmacology because he sees the potential for PCPR to become a world-class pain research program. “That’s clearly why I came here,” says Gebhart,

professor of anesthesiology and director of PCPR, which is engaging the collaborative efforts of pain investigators from the Departments of Anesthesiology and Neurobiology and the Department of Medicine’s Division of Gastroenterology, Hepatology, and Nutrition. “It was clear there were resources and opportunities here that are available at few other institutions.”

Dr. Don Burke with one of his favorite Pittsburghers, granddaughter Griffin

Donald S. Burke, M.D., readily admits he wasn’t looking for a job when his new jobs — yes, jobs — found him. “I was happy doing what I was doing,” says the internationally recognized expert in global health and infectious diseases who had joined the faculty at Johns Hopkins Bloomberg School of Public Health in 1997 after 23 years in the U.S. Army Medical Corps. Yet, he was intrigued when Pitt began recruiting for a director of its Center for Vaccine Research, a major new initiative at the School of Medicine. As the story played out in 2006, he ended up with not only that job but two

others as well: associate vice chancellor for global health and dean of the Graduate School of Public Health. (Ironically, he had previously passed on a nomination to become dean of the School of Public Health at Hopkins.) Motivating Burke’s decision to make the move were the realization that Pitt is “a place on the rise”; the people he met while interviewing here (“I was just very favorably impressed”); the city itself (“Pittsburgh has its own lasting reputation as a steel city… it’s a pleasant surprise to find that it’s different”); and the collective opportunities for him, at the nexus of three interwoven and

collaborative positions, to make significant advancements to vaccine research and public health locally as well as on the global stage. “There is a sense to it,” says Burke, who also is the first occupant of the UPMC Jonas Salk Chair in Global Health. “They are three jobs with different sets of responsibilities, which can be — and ideally should be — synergistic. Having the three jobs simultaneously allows me to take different groups of people with different skill sets and to bring them together. It also gives me some measure of authority at several levels to make things happen.”

DONALD S. BURKE, M.D.

“Having the three jobs simultaneously allows me to take different groups of people with different skill sets and to bring them together.”

NEWS & ACHIEVEMENTS

Dye and genetically coded protein reveal changing concentrations of positively charged calcium ions in a beating mouse heart.

Dyeing to See How Hearts Beat

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hat if cardiologists could one day identify more precisely who is at risk for a fatal heart arrhythmia, know why they are at risk today more than they were last week, and take steps to reduce that risk? Few scientists really understand the electrical system that keeps our hearts ticking reliably, but biophysicist Guy Salama, Ph.D., probes why fatal arrhythmias occur by mapping cardiac voltage and calcium changes. The professor of cell biology and physiology has pioneered the development and use of

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as they move in and out of the cell. By capturing the changing concentration of calcium ions (a strong indicator of voltage) and overall voltage changes in precise environments, Salama is able to show an electrical signal moving across the heart as a wave. Using this technology, he has demonstrated how a myocardial infarction creates a barrier to this wave, potentially setting off an arrhythmia or even a chain reaction of uncontrolled and uncoordinated heart beats called fibrillation. Still to come, Salama hopes to determine the difference between an irregular beat that the heart can handle and one that is life-threatening. With new dyes and the right technology, he also hopes to someday achieve a first: 3-D imaging of voltage changes deep within the heart as well as on its surface.

Thomas E. Starzl Transplantation Institute in 2005, hopes that the tiny sea creatures known as Hydractinia (sometimes called “snail fur” because of their affinity for growing on the backs of hermit crabs) might allow him to explore the mysteries of the innate immune system. The ability of these tiny invertebrates to recognize and even fuse with one another — or, conversely, to reject dissimilar organisms — is thought to hold some clues to what triggers antibodies and other components of the more sophisticated adaptive immune system that plays such a critical role in organ transplantation. Lakkis likens the innate immune system to a giant doorbell that can awaken the adaptive immune system. By studying Hydractinia, he hopes to answer some of the fundamental questions— like what

A Doorbell to the Immune System

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hat insights can a primitive relative of the jellyfish provide to better understand the complexities of tolerance for transplanted human organs? Fadi G.

are the mechanisms that turn the innate immune system on and off—that could apply to humans as well.

Lakkis, M.D., who became

voltage-sensitive dyes and optical imaging systems to observe the basic electrophysiology of the heart, including the movement of calcium ions, which control force generation and change the polarity of heart cells

scientific director of the

Hydractinia, at right, takes on and rejects a larger and incompatible sea organism.

Two New Members of an Elite Cadre

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mong the newest members of the Institute of Medicine, an elite cadre of individuals recognized for professional achievement and contributions to the medical sciences, health care, and public health, are Timothy R. Billiar, M.D., and David A. Brent, M.D., left, and Timothy R. Billiar, M.D. David A. Brent, M.D. Their shared distinction honors individual areas of medical expertise. Billiar, a distinguished trauma and general surgeon, is the George V. Foster Professor and chair of surgery; he is well known for his research on the body’s response to injury and infection. Brent, a leading figure in the study of the risk factors and prevention of adolescent suicide, holds an endowed chair in suicide studies in the Department of Psychiatry and serves as academic chief of the Division of Child and Adolescent Psychiatry at Western Psychiatric Institute and Clinic. Since the Institute of Medicine was established in 1970 by the National Academy of Sciences, only 1,649 people have been admitted to membership, including 15 others from the University of Pittsburgh.

Starzl Awarded National Medal of Science

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f all the words ever linked to Thomas E. Starzl, M.D., Ph.D., and his august career on the frontier of organ transplantation, probably his most cherished appear on a simple, round medallion that says “National Medal of Science.” When news came that he would receive the nation’s highest scientific honor, Starzl responded in typical Starzl style: “I don’t think the medal is being given to me; it’s being given to Pittsburgh and the University.” Yes, both are widely identified with Starzl’s work as a surgeon and a scientist in pioneering the field of

transplant medicine, but it was his own successes here

Starzl’s honor. However, not

over a span of decades that secured his legacy. In fact,

even he is exempt from the building’s strict security, he

it was Starzl’s achievements

says. “There’s a guard who

that opened a new vision of the city and its namesake university for people through-

sits there, and I still have to show my ID.”

out the world. On the occasion of his 80th birthday, Starzl, distinguished service professor of surgery at the School of Medicine and director emeritus of the Starzl Transplantation Institute, received yet another tribute, one that couldn’t be draped around his neck as President George W. Bush had done with the National Medal of Science at the White House. Pitt’s Biomedical Science Tower, a premier research facility that includes an entire floor of laboratories devoted to transplantation

research, was renamed in

Thomas E. Starzl, M.D., Ph.D.

NEWS & ACHIEVEMENTS

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An “Amazing” Network of Cellular Communication

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A Novel Approach

says Amin B. Kassam, M.D.,

to Brain Surgery

professor and chair of neurological surgery. Kassam and Carl H. Snyderman, M.D., professor of otolaryngology, are co-directors of the UPMC Center for Minimally

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f the best way to the heart is through the stomach, then the best way to the brain is through… the nose? For the past few years, Pitt physicians have been working on an innovative brain surgery technique involving none of the usual incisions and facial disassembly. Using telescopic tools in a procedure called endoscopic transnasal brain surgery, they are able to extract tumors and treat other conditions through the nostrils without manipulating the brain, critical arteries, or cranial nerves. “The technology allows us to navigate deep inside the brain in ways that were once thought impossible and operate with greater confidence to ensure the best possible outcome for the patient,”

Invasive and Cranial Base Neurosurgery and pioneers of the endonasal approach, along with Ricardo L. Carrau, M.D., professor of otolaryngology. After the endonasal procedure, patients usually are discharged from the hospital much sooner and with fewer lingering effects than if they had undergone traditional brain surgery. The technique has most recently been successfully expanded from the treatment of adults to pediatric patients.

Dendritic cells interlaced by tunneling nanotubules in a magnified image

ispy, thread-like circuits called tunneling nanotubules interconnect dendritic cells to form an intricate communication network that was little known and even less understood before Simon C. Watkins, Ph.D., professor of cell biology and physiology, and Russell D. Salter, Ph.D., associate professor of immunology, employed some of the Center for Biologic Imaging’s most sophisticated technology to observe how they work. What they saw enabled them to explain that the function of tunneling nanotubules (which are 5,000 times smaller than the width of a human hair) is to trigger an exquisitely swift and long-distance watchdog response among the cells of the body’s immune system to outside incursions. Although the full implications of this discovery are yet to be understood, Watkins says finding that immune system cells use this intricate physical network to relay molecular signals to one another is “quite astonishing.” Salter concurs, noting that the nanoscale distances involved in these transmissions would be equivalent to four or five city blocks. “That’s nothing short of amazing,” he says.

New Departments Add Advanced Technology

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reating new academic departments at a medical school is like adding teams to the NFL; it just doesn’t happen every day. Yet, within one year, the School of Medicine added three new departments: Biomedical Informatics, Computational Biology, and Structural Biology, all of which reflect the school’s growing emphasis on the integration of advanced technology with basic science in some of the most rapidly developing and leading-edge fields of biomedical research. Biomedical informatics starts with data—complex life sciences data—and employs the principles of information science and technology to analyze and manage the data so as to solve specific problems or create useful models of information. Computational biology, on the other hand, starts with a hypothesis and applies mathematical modeling and computational simulation techniques to analyze and achieve better understanding of intricate biological processes like protein folding kinetics. Structural biology uses nuclear magnetic resonance imaging, X-ray crystallography, and other ultra-sophisticated techniques to study the shape, architecture, and dynamics

Michael S. Sacks, Ph.D., left, and William R. Wagner, Ph.D.

of proteins, nucleic acids, and other macromolecules that are otherwise too small to be seen in detail so as to better understand their function and interactions. Not only do these disciplines complement one another, they also enhance the collaborative and interdisci-

technology and the two Pitt bioengineers behind its development, William R. Wagner, Ph.D., and Michael S. Sacks, Ph.D., for the Scientific American 50 awards list for 2006. Thanks to the collaboration of these two researchers, both of whom are associated

plinary environment already

with the University’s

established by the school’s

McGowan Institute for

other departments, which

Regenerative Medicine, the

total 28—for now. Chances are, more are on the way.

elastic, tissue-like scaffold, which is formed by using strong electrical fields to

I’ll Take Biodegradable Scaffolding Material for $500

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n TV’s game show “Jeopardy,” if the clue is “polyester urethane urea,” the correct answer would be: “What’s used to make a new, biodegradable scaffolding material that could one day serve as a tissue-engineered replacement for damaged pulmonary valves and other soft tissue?” Readers of Scientific American should get that one right. The journal’s editors chose this

combine cells and polymer nanofibers, can be modeled to mimic even the complex workings of the human pulmonary valve. They’re now refining this technique to design tissues for other uses. “Although we may not be able to regrow limbs as salamanders do,” Scientific American notes, “the human body does have intrinsic regenerative power, and the discipline of tissue engineering has discovered ways to exploit it.”

NEWS & ACHIEVEMENTS

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Modern Medicine and Natural History: An Opportunity for Reciprocal Illumination

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ucked away in a room of Pittsburgh’s Carnegie Museum of Natural History is a 3-yearold Egyptian who holds a secret. About 2,300 years ago, his organs were removed, his body treated with preservatives and laid to rest, wrapped in white linen and canvas, in a tiny cartonnage brushed with hieroglyphics. No one knows how he died. The mystery of this mummified corpse was highlighted in the School of Medicine’s new Natural History of Medicine course, which is team-taught by leading scientists at the Carnegie Museum. One of the new mini-electives for first- and second-year students, the course is an outgrowth of the museum-medical school partnership called the Natural History of

Medicine Initiative, which is believed to be the first of its kind in the country. The idea for this collaboration came about in conversations between two friends, K. Christopher Beard, Ph.D., curator and head of the museum’s vertebrate paleontology section, and John S. Lazo, Ph.D., Allegheny Foundation Professor of Pharmacology and museum board member. They share an interest in evolutionary biology and thought that a course about the history of disease and injury from an evolutionary perspective would enrich the medical school curriculum. The purpose of the course is to give students “insight into the interrelationships between medicine and natural science, which we believe will enhance their understanding of the scientific discovery process while getting them to think about medicine in new ways,” says Lazo.

“My hope is that students will gain a deeper understanding of human anatomy using an evolutionary perspective,” Beard says. Many contemporary medical issues stem from human origins. For example, the transition from walking on all fours to two hind legs contributed to modern orthopaedic issues (hip, knee, ankle, and lower back pain) and more difficult childbirth. Also, disease-causing microbes constantly

evolve, and it’s important to comprehend how. HIV was initially a pathogen in primates that eventually mutated and crossed over to humans, so grasping basic principles of evolution can help students to better understand how mutations occur in diseases that are currently public health concerns (like avian flu).

Students taking the course can also observe a cancerous tumor in a 150 million-year-old Jurassic dinosaur bone and evidence of gout in one of the museum’s meat-eating dinosaur skeletons. Such observations can lead to fresh ideas about the origins, prevention, and treatment of human illnesses. Medical students won’t be the only ones to benefit from the collaboration. Museum scientists can access Pitt’s computed tomography and magnetic resonance imaging

scanners (rather than breaking apart a skeleton or fossil, a scanner allows researchers to peek inside it less destructively) and electron microscopes. They’ll also have beneficial interaction with the students themselves. “What strikes me most about these medical students is their overall quality. They have a strong background in the basic biological sciences and are swift to engage with new concepts. I’ve gotten several questions from students that have really made me think about things from a new perspective,” says Beard. He hopes that museum scientists and medical students will benefit from “reciprocal illumination.” In the meantime, some additional planned research might provide a clearer idea as to what caused the young Egyptian’s death — without unfolding his death garments or disturbing his quiet sleep.

NEWS & ACHIEVEMENTS

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Obesity Researcher

Potential Therapy for

Looks to Leptin

Rare Immunity Defect

for Answers

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ene therapy might someday become a viable option for treating severe combined immune deficiency, a rare disease of the immune system; but unlocking that potential requires better understanding of B cells, the immune system’s antibody factories, and especially the process of recombination that creates those antibodies. Figuring

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n obesity research, a supposed panacea comes down the pike all the time, so Allan Zhao, Ph.D., associate professor of cell biology and physiology, is cautious when he talks about his work with leptin, a hormone produced by fat cells. Leptin causes people to limit food intake, expend more energy, and lose weight. It’s found in high levels in the blood of the obese, but for some reason, it has trouble in that population getting to the hypothalamus, where it works. Zhao decided to pass human serum through a leptin column, suspecting that whatever bound to leptin could be retarding its progress. Five major protein bands stuck. One of them— C-reactive protein (CRP) — has been found to be abundant in the blood of obese individuals and to suppress leptin’s functions. Zhao wonders whether an agent can be developed to disrupt the CRP/leptin interaction, but he doesn’t expect a quick fix. “Obesity is a complex problem,” he says.

Allan Zhao, Ph.D.

Poetry and Medicine

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hen poet and physician William Carlos Williams was asked why he pursued his interests in poetry and medicine, he replied, “They amount for me to nearly the same thing.” Though the connection between the arts and medicine may not be obvious, many students in the School of Medicine also pursue each with a similar passion, judging by the number of submissions that editors receive for the student literary magazine Murmurs. Funded by the Medical Alumni Association and the Office of Admissions and Financial Aid, Murmurs is produced in the fall, and a CD of student music is created in the spring. When asked why poetry is so popular with physicians (JAMA has a regular column called “Poetry and Medicine,” and

the New England Journal of Medicine sometimes prints poetry), one of the magazine’s current editors, Kevin Proctor, said, “Science is often seen as right or wrong, and there isn’t a lot of room

out what drives and what stops antibody production is the focus of Lisa Borghesi, Ph.D., assistant professor of immunology, whose research has identified the stretch of B cell DNA where recombination begins. She also has

learned that mice without a certain protein (transcription factor E47) show a 90 percent decrease in recombination activity, indicating that this protein plays an important role in the process. “Once we know the specific factors that turn recombination on and off in the mouse model, we’ll look in patients and see if they have those factors,” says Borghesi. “With gene therapy, there may be an opportunity to correct that defect if they don’t.”

B cells in the making grow in tissue culture.

for personal expression.” Poets and physicians are both expected to excel in observation, synthesis, and the creation of a whole from seemingly unrelated parts; many medical schools are incorporating the arts and humanities into their curricula. “Writing’s just a good distraction from school,” Proctor says. “People are looking for a creative outlet outside of studying.”

Workings of the Teenage Brain

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hile no one may ever be able to explain why teenagers don’t clean their rooms, exploring the workings of the teenage brain — why adolescents sometimes put themselves in precarious situations or engage in impulsive behavior, for instance — has won Beatriz Luna, Ph.D., prestigious recognition. She was one of 56 young researchers who gathered at the White House in August 2006 to receive a Presidential Early Career Award for Scientists and Engineers. In addition, Luna received approximately $1 million to continue her research in adolescent brain development as associate professor of psychiatry and psychology and director of the Laboratory of Neurocognitive Development. Her current work, funded through the National Institute of Mental Health, aims to establish a template for “normal” cognitive maturation that can be used to identify impairments like schizophrenia or mood disorders that can emerge in adolescence.

Beatriz Luna, Ph.D.

NEWS & ACHIEVEMENTS

Heart-Healthy Bacon? Maybe Someday

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ou’ve heard of pork — the other… source of heart-healthy omega-3 fatty acids, right? Until now, omega-3 fatty acids, which can improve heart function and reduce the risk of heart disease, have come primarily from dietary supplements or certain types of fish, especially salmon and tuna, which may also carry high mercury levels. A multiinstitutional research team led by Yifan Dai, M.D., Ph.D., associate professor of surgery and a researcher at

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the School of Medicine’s Thomas E. Starzl Transplantation Institute, has cloned transgenic pigs engineered to produce omega-3 fatty acids, providing vast new opportunities for studying the substances’ influence on cardiovascular function, not only in pigs but in humans as well. The key to the development is the transfer of a gene known as fat-1, which creates an enzyme that converts less desirable but more abundant omega-6 fatty acids in the pigs into omega-3 fatty acids. Dai, whose collaborators on this project include transplant pioneer Thomas E. Starzl, M.D., Ph.D., and Rhobert

Evans, Ph.D., from Pitt’s

Graduate School of Public Health plus researchers from the University of MissouriColumbia and Massachusetts General Hospital, says the pigs could also serve as a model for studying autoimmune disorders and diabetes. Although getting them into the food chain is not the current focus of the team’s research (and the Food and Drug Administration would certainly have something to say about that), the bonus might someday be the ability to make bacon that’s actually good for you.

At a World AIDS Day event organized by Susan Wong in Nanjing, 65 pairs of Chinese slippers in the shape of a ribbon represented the 650,000 people in China estimated to be infected with HIV.

Pitt’s Fogarty Fellows Around the World

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lobal health is an increasingly popular topic among Pitt medical students, as evidenced by their recent representation in the International Clinical Research Scholars Program sponsored by the National Institutes of Health’s Fogarty International Center. Yetunde Olutunmbi, Pitt’s 2007 Fogarty fellow, is headed to Tanzania for a year of mentored clinical research at Muhimbili University College of Health Sciences. In 2006, Pitt had three Fogarty students. The program took Susan Wong to Nanjing, China, for work at the National Center for STD and Leprosy Control; Kate Dickman’s fellowship

was at Makerere University in Kampala, Uganda; and Krista Pfaendler was in Lusaka, Zambia, at the Center for Infectious Disease Research-Zambia. All three students were able to acquire funding to extend their stays for another year. Dickman was awarded a Howard Hughes fellowship to continue her studies in Uganda. Pfaendler received additional

support through one of her Fogarty mentors from the University of Alabama, which maintains a large-scale HIV treatment program in Zambia. Wong is now in Beijing as the first student at the Fogarty International Center-sponsored China Collaborative Suicide Research Training Program, with joint funding from the Dean’s Research Fellowship Program and the center.

paw got better too. The injected gene helped suppress the immune response that was causing rheumatoid arthritis, and the affected dendritic cells then emitted exosomes that traveled through the bloodstream and seemed to send the same signal to the other joint as well. Robbins is now working on generating exosomes from immune cells in vitro and injecting the resultant

Exosomes Grab Attention

exosomes into mice as a potentially viable

immunosuppressive

P

aul D. Robbins, Ph.D.,

treatment for all

got interested in exo-

somes by accident. These tiny vesicles, which are emitted from all kinds of cells, were originally thought to be responsible for nothing more than getting rid of cellular junk, but they’re now being studied for their role in cancer, immunosuppression, and as treatment for autoimmune disease. Robbins, professor of molecular genetics and biochemistry, had been looking at modes of gene therapy for autoimmune diseases. After he injected a therapeutic dose into the paw of a mouse afflicted with rheumatoid arthritis, not only did the condition at the injection site improve, but the opposite

manner of autoimmune disease. But why use exosomes rather than cells? Whereas the immunosuppressive attributes of a cell can be reversed in the body, it seems that those of exosomes cannot. They’re a more stable and, Robbins believes, safer method of achieving immunosuppression.

Above right: Once ignored, exosomes are now seen as a potential treatment for autoimmune disease.

NEWS & ACHIEVEMENTS

Enlisting Patients as Partners in Clinical Research

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ewer than 4 percent of people with cancer generally participate in cancer-related studies, says Steven E. Reis, M.D., associate vice chancellor for clinical research. How does this fact affect cancer treatment? How can researchers make the study of health-related issues more attractive to patients who could benefit from the research? Having enough people willing to participate in clinical trials has always been a challenge. Pitt, in collaboration with the University of Pittsburgh Medical Center (UPMC), is implementing a novel approach to combat the dearth of study participants by developing a clinical research registry — a database of people willing to participate in clinical research and an ongoing list of current studies being conducted through the University. The database will be embedded in UPMC’s electronic health record system (eRecord), giving researchers potential access to people who use UPMC’s 400 doctors’ offices / specialized outpatient clinics and 19 hospitals, which account for more than 3 million outpatient visits and more than 167,000 hospitalizations a year. The goals of the registry are to provide all UPMC network patients with educational materials about clinical research and to seek their permission to be contacted for study recruitment. “We see development of the research registry as a natural step toward our vision of extending eRecord to areas such as clinical trials enrollment and epidemiological research,” says G. Daniel Martich, M.D., UPMC’s chief medical information officer. “UPMC has spent more than half a billion dollars building a truly interoperable, longterm electronic health record not only to enhance clinical care and improve quality but also to pave the way for research.” The registry is just one component of Pitt’s new Clinical and Translational Science Institute (CTSI), established with an $83.5 million grant from the National Institutes of Health. Pitt is one of the first institutions selected to receive this award, joining 11 other academic medical centers in aiming to transform how clinical and translational research is done. The purpose of CTSI is to quicken the time it takes for biomedical advances to reach the medical consumer. Other goals are to promote initiatives that ensure patients — especially minority patients and those from underserved populations — greater access to clinical trials; to encourage collaborations that can facilitate the adoption of new medical therapies in clinical practice; to foster the launch of novel technologies; and to promote the training of a new generation of clinical scientists. Creating the clinical research registry is an important part of the translation process. The critical first step is to introduce people to the registry when they check in at a UPMC point-of-service office. They’ll receive educational materials about clinical research and the potential benefits of becoming a research participant. They’ll also be asked to provide written permission to participate in the registry. “We think that asking for consent at first contact—rather than an unsolicited mailing, for example, or waiting for responses to posted requests — is crucial,” says Reis, the grant’s principal investigator and head of CTSI. If patients sign up, their medical records will be matched with inclusion criteria for more than 5,600 Institutional Review Board-approved studies currently going on at Pitt. They’ll receive regular mailings about studies or medical issues that might be pertinent to them and be offered the chance to participate in specific studies. At the same time, safeguards will be established to protect the confidentiality of patient records and to prevent their use outside the registry’s carefully prescribed parameters. Reis hopes the registry helps to create a “research-informed patient.” Many people distrust or have no interest in clinical research, don’t know what its benefits or risks are, or have no idea how it can affect their health care. By removing such barriers, the expectation is that people will develop a vested interest in clinical research because they’ll see how it can translate into better health care. For example, he says, “We don’t have polio in our nation today because of the polio vaccine, which was developed through clinical research.”

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DR. STEVEN E. REIS HOPES THE REGISTRY HELPS TO CREATE A “RESEARCH-INFORMED PATIENT.” MANY PEOPLE DISTRUST OR HAVE NO INTEREST IN CLINICAL RESEARCH, DON’T KNOW WHAT ITS BENEFITS OR RISKS ARE, OR HAVE NO IDEA HOW IT CAN AFFECT THEIR HEALTH CARE. “WE DON’T HAVE POLIO IN OUR NATION TODAY BECAUSE OF THE POLIO VACCINE, WHICH WAS DEVELOPED THROUGH CLINICAL RESEARCH.”

NEWS & ACHIEVEMENTS

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various liver dysfunctions. Before they began collaborating, Perlmutter and Brodsky independently showed that autophagy degrades the enzyme

in 10 percent of patients with A1AT deficiency. Therefore, Brodsky and Perlmutter are now looking for compounds that trigger the autophagic response or prevent protein aggregation in A1AT deficiency and other protein aggregate diseases. They are searching for such compounds with baker’s yeast and with the small roundworm Caenorhabditis elegans; colleagues are helping them create a worm model of A1AT deficiency with protein aggregates and testing compounds to see if any degrade the aggregates without hurting the worm. “We’re cautiously optimistic about our chances of finding some interesting compounds that will have application to a number of protein

inhibitor alpha-1-antitrypsin

aggregate diseases,”

(A1AT), the deficiency of

says Perlmutter.

David H. Perlmutter, M.D., left, and Jeffrey Brodsky, Ph.D.

Working Together to Keep Proteins from Aggregating

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hen they first met, David H. Perlmutter, M.D., Vira I. Heinz Professor and chair of pediatrics, and Jeffrey Brodsky, Ph.D., Avinoff Professor of Biological Sciences, saw each other as potential rivals because both studied a similar area of cellular protein degradation. After realizing that their research and experience would be complementary, however, Perlmutter and Brodsky began working together on ways to keep proteins from aggregating, a process linked to diseases like Alzheimer’s, amyotrophic lateral sclerosis (Lou Gehrig’s disease), and

which can lead to abnormal protein aggregates. They also found that when cells don’t have a normal autophagic response, they are susceptible to greater aggregation when exposed to too much of the mutated protein. They believe that defects in autophagic response could be part of the cause of liver damage

AAMC has established a special Web site, www.aspiringdocs.org, as the primary information portal for this endeavor and developed a series of promotional posters, like the one at left.

Diversity in Medicine

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umbers tell the story: 25 percent of the U.S. population today is composed of African Americans, Hispanic Americans, and Native Americans, yet only 6 percent of the nation’s practicing physicians come from these minority groups. To bolster diversity in medicine, especially among the physician workforce, the Association of American Medical Colleges (AAMC) has initiated a campaign called Aspiring Docs and selected the University of Pittsburgh as one of the program’s four pilot schools, at which particular efforts are being made to narrow the gap between the number of undergraduates from

all major racial and ethnic groups (particularly, but not exclusively, biology majors) and those who apply to medical school. The School of Medicine is engaging in a variety of initiatives to support and publicize this nationwide campaign to change the face of medicine so as to better serve the health care needs of an increasingly diverse American population.

Amphibian Tales

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derived from a pig bladder to regenerate two severed fingertips—bone, blood vessels, nerves, skin, and fingernail. After growing back, the fingertips looked perfect and were perfectly functional. Badylak’s assessment: “It’s really rare. I’m not saying it’s impossible, but nobody would have predicted it [working].” Now, with funding from the Defense Advanced Research Projects Agency (DARPA), he and a team of scientists from throughout the U.S. are reaching for an even loftier goal: regenerating an entire functional digit (joint included) in a mouse — just like a salamander. From this project, they hope to learn much about the genetics of regeneration. The payoff for

alamanders and newts success would be the prospect

can regenerate lost of someday being able to

limbs, so why not us? At the McGowan Institute for

regenerate a fully functional

Regenerative Medicine,

human limb or even vital organs. “We’re hoping to

Stephen F. Badylak, M.D.,

learn principles that will D.V.M., Ph.D., coordinates

a team that hopes to learn how to regrow a mammalian digit. They believe that amphibians can show them how. Badylak, professor of surgery, has already successfully used biologic scaffolding

make many things possible,” says Badylak.

NEWS & ACHIEVEMENTS

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DNA molecules wrap tightly around a histone core, creating a nucleosome. So how do other proteins squeeze in there and interact with the DNA? Sanford H. Leuba, Ph.D., assistant professor of cell biology and physiology, discovered that, on occasion, DNA briefly unravels from the core and stays unfurled long enough for processes such as RNA transcription and DNA repair to occur. The sequence is illustrated at left. Leuba and his team were the first to provide direct evidence of these fluctuations in nucleosome structure — an understanding of molecular mechanisms that adds one more tool to the arsenal for fighting diseases.

Focus on the Basics

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efore second-year medical students begin their clinical rotations and come face to face with that monolithic (and often confusing and demanding) entity called the health care system, they must take a new course, “The Basic Science of Care,” which is designed to help them better understand how the system works (or sometimes fails to work), identify viable solutions to realistic problems or limitations within the system, and develop an appreciation for collaboration among interdisciplinary members of the health care

team in delivering safe, effective, evidence-based medicine. One particular focus of the course is the importance of information technology and communications systems in providing cost-effective, error-free medical care. While the course is required for

medical students, it is open to students from all of the University’s health sciences schools and involves faculty from each of these disciplines: medicine, nursing, pharmacy, public health, rehabilitation sciences, and dental medicine.

earn dual degrees as an M.D. and Ph.D. Pitt’s program, which currently has nearly 100 students enrolled, is also funded by the Office of the Dean. Only 41 such programs across the country receive NIH support. Wiley says the additional funding will give Pitt a further edge in the

A Show of Support

competition to recruit top-

P

level students.

itt’s Medical Scientist Training Program

(MSTP) has received approval for a doubling in the number of student slots

Bubbles to the Rescue

I

magine being able to detect coronary heart disease, noninvasively, decades before symptoms develop. Such was the idea that prompted Flordeliza S. Villanueva, M.D., associate professor of medicine, to pursue her work with microbubbles, inert gaseous bubbles smaller than red blood cells that can course through the blood stream without causing blockage and that, when used

with imaging technology, can reveal blood flow and otherwise hidden processes. Villanueva and colleagues were the first to prove the principle that—with the use of ultrasound—heart disease could be diagnosed in a living being at the cellular level. Microbubbles developed by her research team to make such early detection possible adhere to inflamed cells, which overexpress unique molecules on their surfaces. The shells of

antibodies directed against these molecules, causing them to flock to the inflamed cells. The microbubbles can then be detected with ultrasound imaging. This development, which is now being refined in animal models, may someday be used to detect not only heart disease but also other diseases and conditions, including transplant rejection, tumor angiogenesis, and stem cell activity.

Advancing Biosecurity on the Public Agenda

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s the 2008 elections approach, the Center

for Biosecurity of UPMC wants to ensure that biosecurity issues are “appropriately emphasized and illuminated” by organizing a bipartisan

the targeted bubbles bear Congressional Caucus on Biosecurity to serve as “a focal point for information

funded annually by the National Institutes of Health. The increase from nine to 18 positions will be phased in by 2009 as part of a fiveyear grant renewal. “This is definitely a demonstration of support for the program and a reflection on how well students are doing in it,” says Clayton A. Wiley, M.D., Ph.D., director of the program. The MSTP provides medical students who are interested in biomedical research the opportunity to

Microbubbles, such as those shown here (arrow), may soon be used to detect disease.

Be it ever so humble, there’s no place like a spanking new, $15.6 million apartment complex, right? The Darragh Street Apartments, the latest campus housing facility for medical students, opened in fall 2007 with 148 one- and two-bedroom units, outfitted with amenities, in four-story buildings conveniently located near the School of Medicine and UPMC.

and discussion” for members of Congress and their staffs about biosecurity issues and legislation. The Center for Biosecurity works to advance policies and practices by providing independent research and analysis for decision-makers in government, national security, bioscience, medicine, public health, and private industry. “We plan to brief presidential and congressional candidates on these issues and to prepare recommendations

for improving biosecurity that we’ll offer to the next administration,” says Tara O’Toole, M.D., M.P.H., the center’s director and chief executive officer as well as a professor of medicine. “We’ll work to more clearly articulate the national benefits and opportunities to be gained from greater investment and ambition in biological research and development; and we’ll continue to work on a wide range of key biosecurity challenges.”

Looking for Blood in All the Right Places

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eople undergoing intensive radiation therapy for blood cancers may hold the key to their own treatment. Doctors often reconstitute such patients’ bone marrow; however, the bone marrow stem cells run the risk of already being contaminated with cancer cells. Researchers led by Albert D. Donnenberg, Ph.D., professor of medicine and director of the University of Pittsburgh Cancer Institute’s Hematopoietic Stem Cell Laboratory, have found another source of hematopoietic, or blood-forming, stem cells in human adipose tissue—better known as fat tissue (hey, it should be good for something). After isolating the stromal vascular fraction from adipose tissue, the researchers were able to grow pericytes, cells surrounding small blood vessels, in a blood-culturing medium. Using flow cytometry, they found among these cells many different hematopoietic cells at varying stages of differentiation as well as evidence of progenitor cells that can give rise to all different types of blood cells.

The evolution from student to physician

E D U C AT I O N

34 Scholarly Project 42 Master Educators 46 Simulation Technology 56 New Technologies in Medical Education 58 Standardized Patients 62 Reflections on Medical School

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S C H O L A R LY P R O J E C T

“RESEARCH IS FORMALIZED CURIOSITY ; IT IS POKING AND PRYING WITH A PURPOSE.”

E D U C AT I O N

BECOMING BETTER DOCTORS

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hy, you might ask, is having more than a passing familiarity with research so important in medical edu-

cation and in the practice of today’s medicine? And why

do we feel so strongly about this issue that we have woven

a scholarly project into our curriculum and made it an inte-

gral component of every medical student’s experience here?

The simple answer is tied to the never-ending quest for excellence in the education of would-be physicians. However, simple answers don’t tell the full story, which, in this case, is perhaps best approached from the bottom line: What kind of doctor do you want? Our thinking is that physicians schooled in the analytic process are better prepared than those without such a background to retrieve and critically evaluate the

Case Studies: Five Students and Their Scholarly Projects

information in this week’s JAMA and New England Journal of Medicine —information that can help them determine patient treatments, for instance, or separate advertising hype from established facts in the process of evaluating new drugs. We believe that physicians schooled in the analytic process will listen to a patient’s medical history and complaints differently. Rather than starting with a

As American folklorist and writer Zora Neale Hurston once said, “Research is formalized curiosity; it is poking and prying with a purpose.” For Pitt medical students since 2004, part of that purpose is to meet a new curricular requirement, which affords them considerable latitude for formulating a mentored scholarly project that meets their personal interests. However, all the projects share a common goal, which is to help them become better physicians. Here are examples of the projects being developed by members of the Class of 2008, the first one required to partake in this “formalized curiosity” process.

set of memorized characteristics and trying to fit the patient into one pathogenic category or another, they listen to all the facts the patient provides and put them together anew. Even if the outcome turns out to be familiar, the realm of diagnostic possibilities is much broader and the practice of medicine much richer than when it is based simply on rote recognition of symptom patterns. We also contend that physicians schooled in the analytic process are more likely than others to get to the bottom of a case and to yield creative clinical decisions based on solid evidence when symptoms don’t fall into common patterns and that they’ll be better equipped to deal with the rapidly changing developments that have become a hallmark of contemporary medicine. So, once again, what kind of doctor do you want?

--Beginning with the Class of 2008, which started medical school in 2004, a scholarly project has been incorporated longitudinally throughout our curriculum and has been broadly defined to provide a wide range of opportunities to appeal to individual students’ interests and aspirations.

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36

S C H O L A R LY P R O J E C T

Some students select traditional laboratory-based or clinical research experiences, while others opt for less obvious choices. The goal in every case, however, is to enhance their ability to think independently and critically and, thereby, become better equipped to practice medicine in the 21st century. This goal is achieved initially through course work designed to teach the fundamentals of deductive reasoning and analytic thought in the application of scientific principles, followed by the establishment of a working relationship with a faculty mentor, whose role is to advise and guide the student throughout the process. The intent is to expose students to the mechanics of scientific investigation; teach them how to develop a hypothesis and how to collect, analyze, and interpret data to support that hypothesis; encourage them to pursue research opportunities; and, ultimately, help them better understand the structure of thought underlying the practice of medicine. In the end, as a requisite for graduation, they are expected to produce a scholarly project that is deemed to be sufficiently meritorious and substantive. Some students might find the experience so rewarding that they pursue a career as a physicianscientist—the decline in the number of which has become an issue of growing concern for the future of biomedical research. Others will simply develop a better appreciation for what it is to do research and engage in scholarly activity, with the result that they become more capable and skillful physicians.

--While a limited number of other medical schools have incorporated similar research projects into their programs, our scholarly project differs in several significant respects. One hallmark is the thoroughness with which we prepare students to undertake a scholarly project, regardless of whether it involves basic or clinical research, population-based research, or a nontraditional endeavor. Our curriculum leads students through a sequence of courses, examples, and creative implementation steps as well

Kristin Robbins To create a better vaccine, “you have to start somewhere,” Kristin Robbins says, and that means dealing with basic science, which she enjoys. “I kind of like getting in on the groundwork,” says Kristin, who has a degree in genetics from the University of California, Davis, and experience working in a biosecurity lab at the Lawrence Livermore National Laboratory. With that background, it’s easy to see why hardtack science would interest her and how that interest would influence her selection of a scholarly project. Under the mentorship of Gerard J. Nau, M.D., Ph.D., an immunologist with expertise in infectious disease, Kristin is exploring how to develop a more effective vaccine against tularemia, a relatively uncommon but highly infectious and easily spread bacterial disease. Spurring her interest are the dual facts that tularemia’s virulent properties make

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37

it a potential biological weapon and that the current vaccine made from a live strain of the disease’s pathogen, Francisella tularensis, is not approved for widespread use in the U.S. Kristin’s hypothesis is that a safer, more effective vaccine can be developed by exporting immunogenic proteins from the bacterium to create a more potent immune response. The process of testing her hypothesis has begun; “I should have the results from at least one immunogenic protein by the end of this year,” she reported in early 2007. Kristin admits to having “a fondness for research” but hasn’t determined how much a part of her career it will be. Doing research “helps you figure out the questions to ask and how to approach those questions,” she says, adding that it parallels somewhat the experience of a clinician who faces a challenging case and must go about trying to solve it; the skill set is similar. Not only that, she says, but research is essential to clinical medicine. “It’s important to have research in order to move forward and continue to develop the kind of treatments that the public expects from us.”

as practice in scientific writing to give them the skills needed to successfully conduct scholarly work. This preparation is particularly important because today’s medical students matriculate from a broader array of backgrounds and experiences than in genera-

Doing research

tions past, and so they might not have been previously exposed to the basic tools of scientific inquiry. By integrating mandatory didactic components of the program throughout the curriculum, we can maximize the benefits of this experience.

“helps you figure out the questions to ask

Further, the mandatory aspect of the scholarly project doesn’t make it unique but certainly among the more exclusive programs now being offered.

and how to approach

Finally, regular, periodic checkpoints of students’ progress throughout the fouryear process, an emphasis on developing strong faculty mentors to ensure the program’s ongoing success, and creative use of electronic technology to foster learning and mentorship are among its other distinctive elements. The scholarly project represents a novel (and perhaps even prototypical) way to increase the number of medical students who pursue research-based careers or clinical careers grounded in evidence-based medicine—and those are the kinds of doctors we want.

those questions.”

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S C H O L A R LY P R O J E C T

Physicians must be able to think critically, develop a plan of action, and solve the unknown— skills that doing research can engender.

Brian Dontchos

Amanda Christini

Before Brian Dontchos came to medical school, he spent two years in a job harvesting cartilage allografts from cadavers for organ donation. In doing so, he learned how sensitive chondrocytes, or cartilage cells, can be. The allografts must be captured within 48 hours of death and kept cold for up to two or three weeks to prevent bacteria growth while donor screening and microbiological cultures are performed to ensure the safety of the recipient. However, studies have shown that cold can diminish the chondrocytes’ viability. Another variable, which has not been explored as much, is the pH of the solution in which the allografts are stored pending transplantation. So, when Brian, who has a biology degree from the University of Denver but little background in biomedical research, needed a topic for his scholarly project, he drew on his work experience, and, with the help of Constance R. Chu, M.D., orthopaedic surgeon and mentor, he designed a study titled “Enhancing Human Chondrocyte Viability.” What he found and subsequently reported in an article submitted to the Journal of Orthopaedic Research is that adding CO2 to the solution can provide the pH levels that the cartilage cells require; alternatively, he determined that using storage media that maintain the requisite pH can also work. Admittedly reluctant at first about the scholarly project requirement, Brian says it turned out to be a positive experience: “I was actually excited about it when I first came up with the idea and my mentor was willing to help.” In caring for patients with wide-ranging problems during his clinical rotations, Brian says he has learned that physicians must be able to think critically, develop a plan of action, and solve the unknown — all of which are skills that doing research can engender.

Amanda Christini is puzzled why all health care workers aren’t willingly immunized against influenza each year. The reality is that only about 40 percent of them are vaccinated, according to nationwide studies, which have documented the dangers of nosocomial transmission of the flu, especially to high-risk hospital patients. Based on nearly 10 years of experience working in the biotech arena, most recently in business development of vaccines and immunotherapy, Amanda brought an interest in the topic with her to medical school along with a biology degree from Tufts University. Her mentor, Karin E. Byers, M.D., an infectious diseases specialist, helped her formulate the focus of her

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scholarly project, which is designed to gauge vaccination rates and motivating factors among various groups of health care workers. The study involves 1,042 workers at UPMC Presbyterian, UPMC Shadyside, and Children’s Hospital of Pittsburgh of UPMC. The results, as published in Infection Control and Hospital Epidemiology, show that the groups of health care workers with the most patient contact are the least likely to be vaccinated and that approximately half of the health care workers have come to work with flu-like symptoms. To boost compliance rates among various groups of health care workers, the report suggests educational initiatives targeting the benefits of immunization as well as ways to counter prevailing misconceptions. “What you really have to do is win people over,” Amanda says. She notes that today’s medical students recognize the importance of research experience to be competitive in their residency applications. “It’s actually nice that there’s a formal structure now that can support people to do the work they need to do anyway and would have done on their own,” she says, adding that coming from an institution with such a high reputation in research gives Pitt medical students clout as they approach the next phase of their education.

“There’s a formal structure now that can support people to do the work they need to do anyway.”

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Yvette Tanhehco Yvette Tanhehco came to medical school with a Ph.D. in biochemistry and cellular and molecular biology from Johns Hopkins University and considerable research experience in viral oncology. She wonders if the time she must devote to a required scholarly project might not, in her case, be used differently; but with lemonsinto-lemonade optimism, she admits to seeing the benefits of the experience. Yvette’s project is based on the premise that individuals with Down syndrome experience obstructive coronary artery disease less often and have a lower mortality rate from atherosclerotic cardiovascular disease than the general population. What she’s doing in her project, with guidance from cardiologist Steven E. Reis, M.D., her mentor, is comparing serologic markers of angiogenesis,

“I think there’s a benefit to making students do research, to having a scholarly project... it allows you to think creatively, and that’s the main reason I love research.”

S C H O L A R LY P R O J E C T

inflammation, and endothelial activation as well as atherosclerotic risk factors like lipids and glucose in two groups of adults, one with and the other without Down syndrome, to determine whether the levels of the markers differ. Yvette says the ultimate benefit, which lies beyond the limited scope of her project, would be the insight to develop new therapies to better protect the general population against coronary artery disease and atherosclerosis. Unlike the basic science with which Yvette is most familiar, this project allows her to explore something new: clinical research, which means learning to conduct a clinical trial, write an Institutional Review Board application, recruit subjects, collaborate with physicians, and follow the research protocol — all of which she sees as pluses. Yvette adds, “I think there’s a benefit to making students do research, to having a scholarly project, because it allows you to think creatively, and that’s the main reason I love research.”

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“My views on it are that this is only going to help us…it makes us better candidates …it’s making us better physicians.”

Sheena Jain Sheena Jain is clear how she feels about the scholarly project program. “Personally, my views on it are that this is only going to help us,” she says before ticking off what she sees as its benefits. Developing and testing a hypothesis, learning how to read and critically assess the literature — what’s relevant, what’s not, and what information might be useful in dealing with patients — it’s all valuable. And in competing for residency slots, “it makes us better candidates,” says Sheena, who studied chemistry and biochemistry at the University of Virginia before returning home to Pittsburgh for medical school. “I think it’s making us better physicians.” Sheena is unsure if she’ll become a physicianscientist someday (if not, it’s because she likes the clinical side of medicine so much), but she knew that she wanted to do some research in medical school. For her scholarly project, Sheena chose the field of radiation oncology, which interests her as a career. Her mentor, Sushil Beriwal, M.D., a clinical assistant professor of radiation oncology, suggested several topics, which she read about and then chose one to tackle beginning the summer after her first year: an assessment of intensity-modulated radiation therapy (IMRT) as adjuvant treatment of endometrial carcinoma. The preliminary analysis, as Sheena, her mentor, and others have reported in Gynecologic Oncology, was “excellent local control and low toxicity” based on a study of 47 patients treated with IMRT (although they noted that longer follow-up and more patients are needed to ascertain the treatment’s long-term benefits). Sheena says she approached this research experience with a desire to learn more about applying the scientific method to the field in which she hopes to pursue her clinical training. “I was successful in achieving that goal (and others) through the scholarly project program, so I’m grateful to have had that opportunity here at Pitt.”

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M A S T E R E D U C ATO R S

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GRABBING THE GOLDEN APPLE

J

amie Johnston, M.D., punctuates his slides on renal transport with photos of himself in high school (the hair is awesome). Richard Steinman, M.D., Ph.D., uses a trading card game in which paired students attack or defend one another armed with an assortment of pathogens, cancers, defense agents, and health status modifiers.

Jules Rosen, M.D., has developed a series of interactive videos to

demonstrate the subtleties of geriatric psychiatry; and, in teaching embryology and development, Cynthia Lance-Jones, Ph.D., still loves the immediacy and illustrative opportunities of the classic chalk talk. All four are members of the School of Medicine’s Academy of Master Educators, established in 2005 to recognize and reward excellence in education, advance education through innovation, support and promote scholarship in the field of medical pedagogy—and just give educators a chance to think about why teaching turns them on. Getting into the academy requires far more than knowing the secret handshake. Each of the group’s 55 members (six of them charter members) had to assemble an educational portfolio that dwarfs War and Peace outlining his or her educational philosophy and teaching goals (this component, paradoxically, limited to 500 words); an overview of educational activities and accomplishments; examples of educational products like curricula, assessment instruments, and Web modules; and a summation of teaching evaluations. All of this info is evaluated by an Academy Membership Committee composed of the applicants’ peers—arguably, their toughest critics— with membership recommendations going to the vice dean and then to the dean for a final decision. The reward for completing this gauntlet? A five-year appointment to the academy and a supplemental incentive payment, with renewal of the appointment based on educational productivity and excellence.

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Pitt is neither an early adopter of medical education as a subspecialty in its own right nor a school that’s behind the curve of educational innovation. Today, Pitt’s School of Medicine is clearly a true believer. “Pittsburgh has been progressive in how we think about the value of the clinical and educational experiences,” says the academy’s academic director, Steven L. Kanter, M.D., the School of Medicine’s vice dean. “We want our academy to accomplish something meaningful and every

VOICES:

ACADEMY

member to be active.” One way in which the Pittsburgh academy differs from other programs is that its focus is not limited to medical student education. Rather, while it recognizes faculty who teach medical students, it also includes those who educate and train Ph.D. students, interns, residents, and both clinical and post-Ph.D. fellows. Pitt’s academy covers all possible teaching venues from the large lecture hall to the small group session, from the laboratory bench to the patient’s bedside. Even the hallways are frequently the loci for one-to-one teachable moments. The vanguard institution in what has been called the “academy movement” was probably the Medical College of Wisconsin, which formed its Society of Teaching

Once you have their attention, you want to inspire them to learn. PETER F. DRAIN, PH.D. Assistant professor of cell biology and physiology

If I, as an educator, want students to be responsible for their own education, then I must engage them in the process through active learning activities and respect their contributions to the learning environment and process. JULIE A. DeLOIA, PH.D. Associate professor of obstetrics, gynecology, and reproductive sciences

Scholars in 1990, with the goals of mentoring junior faculty, promoting educational scholarship, advocating for educational issues, and recognizing teaching excellence. Since then, a number of medical schools have followed Wisconsin’s lead (but still probably fewer than 20). Among them are the University of Illinois at Chicago (1996), the Mayo Clinic College of Medicine (1998), the University of California, San Francisco (2000), the University of Florida (2000), Baylor (2001), Harvard (2001), Mount Sinai (2001)—and now Pitt. The formal Academy of Master Educators follows the school’s creation of a defined faculty path for the clinician educator in 2001.

The key thing is using the right tool at the right time and the right place. SAMUEL A. TISHERMAN, M.D. Associate professor of surgery and of critical care medicine

Nephrologist Jamie Johnston (he of the big high-school hair) was the first member of Pitt’s Academy of Master Educators and currently chairs the academy’s membership committee. “We’re newborns,” he says and credits Kanter as being the modest but still proud father of the rapidly developing enterprise. Johnston sees two themes emerging from the Academy of Master Educators—the mentoring by senior faculty of their junior colleagues who are interested in education, an emphasis that also gives the senior faculty more and different educational opportunities, and connecting a broader swath of faculty members with peers who have been singled out for their teaching excellence. Kanter is now moving the academy to the next level through four task forces designed to jump-start a few key activities; these ad hoc groups will focus on faculty development in medical education, the creation of a virtual center for evidence-based medicine education, mentoring for junior faculty members who are interested in developing careers as clinician educators, and teaching residents to teach. Meanwhile, the academy has offered validation, affirmation, and a strong peer network to its members. Steinman, Rosen, and Lance-Jones, while using different words, would likely echo Johnston when he says that he finds teaching addictive— “It’s like a comedian feeding off of laughter,” he says. “To maintain knowledge, you need to use knowledge. Abraham Flexner said that in 1910—teach in the clinic and work in the laboratory.” He sums up why he’s hooked on teaching: “To see the light of understanding is as important as seeing a patient get better.”

Learning is mostly visual and auditory only during the first two years of medical school, whereas suddenly, in third year, you’re smelling the patient, you’re hearing the patient and touching the patient on so many levels where so many parts of your brain are receiving information, and the permanence of learning is so much better. You’re no longer learning just to pass a test, and it’s pretty gratifying to see that stuff is sticking with the students. JONATHAN D. FINDER, M.D. Associate professor of pediatrics

Our job as formal educators of medical students is to help them understand, retain, and use vital scientific and medical information. A good oral presentation should help medical students do this; but, if we give them a lot of parallel documentation, are we sending the message that listening and focusing on a lecture is not important? CYNTHIA LANCE-JONES, PH.D. Associate professor of neurobiology

Learners are different. Some students need a structure, and they can hang facts on it, and other students need to discover in a messy way and synthesize later. KATHLEEN McINTYRE-SELTMAN, M.D. Professor of obstetrics, gynecology, and reproductive sciences

Showing your passion is vital. FRANK J. KROBOTH, M.D. George H. Taber Professor of General Internal Medicine

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This is not a hand — not a human hand, anyway. It belongs to SimMan, one of WISER’s life-size and lifelike patient simulator mannequins.

VIRTUAL TRAUMA, REAL LEARNING

W

hat do you usually think about when you’re driving? The weather, the traffic, the annoying morning radio deejays? What you probably don’t think about is

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Winter Institute for Simulation Education and Research (WISER) is

S I M U L AT I O N T E C H N O LO G Y

driving itself, the complex mechanics of steering and braking, the rhythm of watching traffic from all angles. The actions that constitute “driving” are so deeply engrained that they rarely penetrate your conscious thoughts, even though the stakes can be high if you don’t perform them correctly. Now think back to the very first time you got behind the wheel of a car. You probably studied hard to prepare yourself for that moment, watching videos in driver’s education class and memorizing the manual of traffic rules. But even if you aced your written driver’s test, nothing truly prepared you for the mental and physical experience of navigating a 3,500-pound vehicle through high-speed traffic. Those first few times on the road, you were acutely aware of every acceleration and turn—yet you were far more likely to make a serious mistake than you are now as an experienced driver. In medicine as in driving, there’s no substitute for practical experience. That’s why the greeting on the Web site for the Peter M.

a quote from the Chinese philosopher Confucius: “I hear and I forget. I see and I remember. I do and I understand.” WISER is one of the world’s leading academic medical simulation training centers, specializing in the creation of extremely realistic scenarios in which medical students and other health care professionals at all career and training levels can safely learn, practice, and perfect crucial procedures before performing them on actual patients. Equipped with the latest in computer technology and mannequin simulators, the 12,000-square-foot WISER facility allows students to achieve mastery through repetition of medical procedures. “WISER can get people ready so they can avoid making mistakes,” says Paul L. Rogers, M.D., professor of critical care medicine, professor of medicine, and director of a number of student simulation courses. “We’re trying to teach them to be unconsciously competent, to take them to a level where they automatically know what to do and how to react in a critical situation. And we don’t stop practicing until every single student gets to that level.” All Pitt medical students spend a minimum of 25 hours in simulation training activities, and two-thirds of them opt for additional elective time to develop mastery of resuscitation, defibrillation, auscultation, and other clinical skills. The following scenarios illustrate what medical students can experience in just 15 minutes at WISER.

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10:00 AM

10:12 AM

10:15 AM

Ryan checks on the placement of the monitor attachments.

If intubation doesn’t work, the next step is an emergency airway puncture.

Ryan focuses on his patient.

“WE’RE GOING TO GIVE YOU SOME OXYGEN TO HELP YOU BREATHE, OK, SIR?” THE PATIENT IS EXTREMELY SHORT OF BREATH, HAS AN ELEVATED HEART RATE, AND IS HYPOTENSIVE.

10:07 AM

Ryan Brannon concentrates on the correct placement of an endotracheal tube after the patient stops breathing entirely.

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10:37 AM

10:42 AM

10:45 AM

Team leader Candace Jones, hoping for an improvement in the patient’s vital signs, checks the monitor.

Two of Candace’s team members continue cardiopulmonary resuscitation ...

. . . by providing ventilations and chest compressions.

“AS TEAM LEADER, YOU HAVE TO PRACTICE MAKING SURE YOU ASSIGN SPECIFIC RESPONSIBILITIES TO SPECIFIC PEOPLE AND GIVE THEM SPECIFIC INSTRUCTIONS. IT’S UP TO YOU TO CLOSE THE LOOP.” A HOSPITALIZED PATIENT GOES INTO SUDDEN CARDIAC ARREST DURING A ROUTINE LAB PROCEDURE.

10:50 AM

The readings on the wall-projected monitor indicate the patient’s return to cardiac stability as Shilpa Patel, part of the hastily assembled code team, listens to feedback from the scenario facilitator.

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5 2 52

11:02 AM

11:06 AM

11:13 AM

Observing classmates get caught up in the drama as ECG monitors are attached to the patient.

Marcus, the exercise leader, monitors his teammates during the intubation.

A live video feed provides SimMan’s operator with an unimpeded view of the action, which is recorded for later student review.

“WE HAVE TO INTUBATE. I NEED A NO. 4 MAC BLADE, A NO. 8 ET TUBE WITH A STYLETTE, AND A 10CC SYRINGE.” THE PATIENT, A CAR ACCIDENT VICTIM, IS UNRESPONSIVE AND HAS NO PULSE.

11:09 AM

Animesh Sabnis watches as a colleague feels for expiratory air, while Marcus Hoffman listens to the stomach to rule out accidental insertion of the breathing tube into the esophagus. Candace Jones is ready with the ventilator tube connector.

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11:24 AM

11:32 AM

11:47 AM

11:35 AM

With the help of a wig and a few interchangeable parts, SimMan can become SimWoman.

Flexible joints allow this SimMan, one of 22 patient simulators used at WISER, to “relax” in a hallway chair.

Follow-up discussion reinforces the learning process.

Paul Rogers, M.D., heads out to debrief the students at the end of the session. The WISER facility was specifically designed to allow facilitators to simultaneously instruct students and relay moment-to-moment changes to the scenario operator.

“I ALREADY KNOW HOW TO MEMORIZE MATERIAL FROM A BOOK. THIS COURSE HAS TAUGHT ME HOW TO THINK ON MY FEET.” BEHIND THE SCENES

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S TA N DA R D I Z E D PAT I E N T S

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REAL PEOPLE IN HOSPITAL GOWNS BUT NOT REAL PATIENTS

W

hen Alfonso Barquera moved to Pittsburgh from Mexico to study English and get an edge in a rapidly

globalizing economy, he became interested in the expe-

riences of his fellow immigrants in the city’s growing

Latino population. Many of the immigrants he met felt

disconnected from the city because of language and cultural

barriers; couldn’t find welcoming, affordable health care; and were homesick for far-away friends and family. Barquera connected with their stories on a personal level and even used their experiences as research for his master’s degree in anthropology. He wanted to help improve the lives of Mexican immigrants, so when the School of Medicine’s Office of Medical Education went in search of people with bilingual skills to work in its standardized patient (SP) education program, Barquera saw it as an opportunity to serve the immigrant community in an unusual way. “I know what it’s like to feel like an outsider in the U.S. health care system, and medical students need to be prepared to interact with someone who may not know what to expect when they go to a doctor here. I like being an SP because I can help students know more about Latinos and our cultural differences,” says Barquera. SPs are trained by the School of Medicine’s Advanced Clinical Education Center to portray patients in health care situations (often one-on-one patient physical exams) with medical students. Their portrayals of patient cases are invaluable steps in teaching students how to perform in clinical settings. Barquera isn’t the only SP motivated to improve the quality of communication between doctors and patients—one of the key benefits of the SP experience for students. Bruce Hill worked as an SP for many years and recently returned to the work after he was diagnosed with diabetes in 2001. Being a patient himself helped Alfonso Barquera

“I KNOW WHAT IT’S LIKE TO FEEL LIKE AN OUTSIDER IN THE U.S. HEALTH CARE SYSTEM. . . .

I CAN HELP STUDENTS KNOW MORE ABOUT LATINOS AND OUR CULTURAL DIFFERENCES.”

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S TA N DA R D I Z E D PAT I E N T S

TODAY, PITT’S PROGRAM HAS 92 SPs BETWEEN THE AGES OF 18 AND 77 WHO

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ARE COMMITTED TO CONTRIBUTING TO THE BETTERMENT OF HEALTH CARE.

him realize how vital trust is in the relationship between patient and doctor and how

Although some SPs are actors, they aren’t expected to create a character; in fact,

essential it is in the recuperative process. “Patients have to feel that doctors respect

they’re told not to consider their interaction with students as a theatrical performance.

them and their medical issues and that the patients themselves are a part of the healing

“We see them as highly skilled workers, not actors. We train them on exactly what to

process. Their emotional states have a great impact on how well, or quickly, their

say and how to respond according to what ailment the patient they’re portraying

health improves,” says Hill. He likes that his work as an SP could help real patients

has. And they do it very well,” says John F. Mahoney, M.D., associate dean for medical

someday through his interactions now with future doctors.

education and associate professor of emergency medicine. SPs portray real cases

In the late 1990s, the use of SPs at medical schools blossomed nationally after several studies proved they could be used with rigor and great reproducibility. Pitt’s

adapted for training purposes so students can apply all of their learning to the clinical setting and learn to think on their feet before they treat actual patients.

School of Medicine created its own SP program and figured out how to use SPs to

SPs are used in conjunction with specialized simulation technologies, like the

teach its students. Today, Pitt’s program has 92 SPs between the ages of 18 and 77.

high-fidelity, electronic pelvic examination models used to teach students how to

Many remain for a long time; one person currently in the program has worked as an

perform a pelvic exam. Some highly dedicated, specially trained SPs participate in

SP for 13 years.

gynecological, genital, and prostate exams. “These are people who are committed to

Before dealing with students, as they do regularly throughout the four years of

contributing to the betterment of health care. For students to be able to gain experi-

medical school, SPs are required to have at least 14 to 16 hours of basic training; and

ence in more sensitive exams on real people, but not yet real patients, is amazing. The

each medical school course in which they are involved requires additional training.

students see that as a gift,” says Fulmer.

“One course involves actually being taught how to perform a physical exam,” says

At a practice testing session, she briefed first-year medical students as to how the

Valerie Fulmer, trainer/educator for the standardized patient program. “SPs spend

afternoon of physical exams would work. When she explained that SPs would be

20 hours with a nurse practitioner and learn how to do things like take blood pres-

watching students’ ability to accurately measure liver spans, some students looked at

sure readings and test reflexes; they also learn medical terminology and how to give

each other with surprise. “Oh, yes,” Fulmer said. “We’ve trained them. They will

students feedback. Then they spend additional time studying the material at home,”

know exactly where their livers are.”

she says.

In addition to knowing where his liver is, Barquera knows he is helping other

Learning to perform physical exams enables SPs to know whether or not students

people in the immigrant community as well as the medical students. “I like to see the

are performing them correctly, whereas learning to evaluate students fosters the

students get more comfortable with me as we move through the exam. I also like

ability to provide consistent and fair assessments. “Being an SP is harder than I thought

feeling that other immigrants might have an easier time at the doctor’s office

it would be. You aren’t just portraying a character; you also have to have one ear and

because of the training I’m doing,” he says.

one eye always on what the students are doing so you can give them appropriate feedback,” says SP Debbie Berkovitz. Students are evaluated on a point-by-point checklist and given feedback on what they did incorrectly, what they missed, and how they interacted with the patient.

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­­You did it—with hard work and support from family and friends. The University

My reflections on Medical School Thomas Conlon, M.D. The story of a medical student is not easily captured. It is, however, a powerful and compelling story, one that physicians will readily recognize and that those who have never experienced medical school can never really understand. Thomas Conlon, M.D., a member of the Class of 2006, offered a glimpse into that experience in remarks he made at the Medical Alumni Association’s annual luncheon for graduating medical students in May 2006. Following are some highlights of his reflections that day to his classmates.

of Pittsburgh, which has one of the finest medical schools in the nation, opened the door for you to attain your dream. And so, there you are, Day No. 1. You’re amazed by the diversity of your classmates, not necessarily in terms of race or gender, but rather the dynamic personalities of those around you, of how they carry themselves so differently but with such a presence. At the White Coat Ceremony, the traditional start of medical school, you sit in your sparkling new white coat and hear the dean describe the honor and privilege of a career in medicine—a sentiment that echoes throughout the program. The portraits of distinguished physicians surrounding you on the walls of the auditorium, the reading of the Hippocratic Oath, the flashing cameras of proud parents—it all seems unreal. Your dream of making it to medical school is realized, but it’s just the beginning. What an honor and privilege it would be to make it to the end. *** As first year rolls on, you find that, while you were a star in college, you’re struggling to remain average here. You find that you’re jealous of those who go out all the time and still do well, or you’re jealous of those who don’t have kids because a family takes up so much precious time. Or maybe you’re at the top of the heap, and no one can imagine the strain of living up to continued expectations. You find that you don’t talk to friends from home as much as before, because, quite frankly, they just can’t understand. Or you’re in a long-distance relationship that is strained because you know that every hour you aren’t studying could mean another point off your test, and you can’t afford that—but, of course, your boyfriend or girlfriend doesn’t understand. Or you go home to your spouse and—although you thought it would be a welcome thing to have someone outside the medical world around—you find yourself becoming more detached and the relationship fraying, with no time to reconcile differences. Your parents call, but

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they don’t understand the world of medicine—or, conversely, one of them is a practicing physician and keeps telling you they understand, but they’re not here, and they don’t know. Your frustration translates into complaining—about the facilities, about the quality of lectures and the minutia you have to memorize.

blue collar, a no collar, a broken hip, a stage-four cancer, a 10-year-old, a 100-

You’re completely enveloped by the world of medicine.

year-old. Suddenly, those feelings that you had so long ago, that you’d almost

***

forgotten, come alive—but they’re so much more real than you remember. ­­

The end of second year comes, and you have to sit for boards. To prepare for

You only knew this feeling vaguely when you applied to medical school and

them, you get a suggested study plan—an eight-week schedule of insanity,

tried your best to put it into words when asked, “So, why do you want to be a

which you scoff at and discard for your own schedule, which turns out to be 10

doctor?” Now, here it is, and words don’t suffice. In that moment, you feel a

weeks of even greater insanity. This one test determines whether you can be an

new burden. You look into those eyes, and they read of fear, of realized mortality,

orthopod or a neurosurgeon, whether you’ll be able to match someplace you want

of age, of experience, and those eyes look to you for help. In that moment, burden

for residency, whether you can return home to your family and appease your

changes to responsibility, and you’re surprised to realize that you want nothing

spouse. As for everyone, the test finally comes and goes. Afterwards, you drive

more than to embrace it—the whole thing. In that same moment, you gain some

to a friend’s cabin in the middle of nowhere, where you can sit with a fishing

understanding of those first two years of medical school, that they provided you

rod between your legs and a glass of “milk” at your side, finally able to feel like

the intellectual and emotional framework with which to approach this newfound

you’ve escaped. That’s when it hits you—you don’t really know if you like the

responsibility.

person you’re becoming.

***

***

It’s 4:30 in the morning, and you wake up tired but ready to roll. You hop on ­­

Clinical rotations begin, and you don’t know the computers, and you’re not

the bus, and, though you’ve thought about how tough you’ve had it the past ­­

answering the attending’s questions right, and you’re worried about the test being

few years, you look at the worn faces of the janitors, the security guards, the line

a shelf exam, and you’ve got to go into the patient’s room right now to get your

cooks, the public works folks, and you realize the difference between people

history and physical so you can finish one to turn in. You sit down at the bedside,

who “go to work” and what you get to do. As you get off the bus, the driver, as

shuffle some papers, look at your watch, lift up your head…and your eyes meet.

always, says, “Have a nice day,” because that’s what they do in Pittsburgh, and

They are the eyes of a male, a female, a Hispanic, a Caucasian, a white collar, a

even though it’s Wednesday and summer and 4:45 in the morning, you blurt out, “Go Stillers,” because, well, that’s what they do in Pittsburgh. *** You’re in Children’s Hospital, and you watch as 2-year-old Sally, who came in with a septic joint, waddles with her back to you, her little hand engulfed by her father’s massive paw, she with only a diaper, and you can’t help but smile. You’re at the VA, and there’s old Mr. Perkins with his IV pole and his back to you in the hall, gown on, but he with neither a diaper nor undergarments, and again you

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finding your center, taking the worst of the day and making it hilariously funny. These are the moments you cherish most. can’t help but smile. You’re at Western Psych, and you give the rundown on a

***

patient to an attending only to have him look at you with hesitation. You’re not

Before your day ends, you remember you need to call Joe, one of your closest

supposed to make breakthroughs, but you know, deep down, that you actually

pals from college but someone you’ve talked to only sparingly recently. He asks

connected with the patient. You’re on ortho rounds, and you just benched 250.

you about school, and you tell him that it’s brutal, hell, torture—all the words

You’re in surgery, and you cut that fascia really well (or whatever gets surgeons

you’ve used in the past—but he knows you love it. For the first time in months,

excited). You find that attending who loves to teach and does it in such a way

you stop yourself mid-sentence and ask, for real this time, “Joe, how the heck are

that you actually learn, and you really want to go home and read to continue the

you?” because it dawns on you that it’s unfair to ask people to walk in your shoes.

process at another level. Not only do some doctors find time to teach, they also

Nobody can entirely understand your experiences, nor can you truly understand

allow you to peek into their lives. They’re mothers, fathers, brothers, sisters, and

theirs. You find that your friends have been walking side by side with you, but you

friends who like to go to the opera, fly fish, and watch football or American Idol.

have been setting the course. It’s time to walk with them for a while and let them

They’re real, and they let you feel real, too—that it’s OK to be fallible, OK to

take you where they want to go.

enjoy life outside of medicine. For the first time, you feel like you can be part of

***

their community.

You finally get home and check the alarm to make sure it’s set for…oh, four hours

***

from now, and turn on the radio to make sure the volume is high enough when the

It’s 5:30 p.m., and you’re getting out a little early because it’s short call. All

sports report reminds you that yes, it’s true, the White Sox really did win the Series

your patients are tucked in, and you’re trying to figure out what to make for

and are world champions. You can’t wait to wake up tomorrow.

dinner when your pager goes off. You approach the phone hesitantly because

***

this call might cause you to stay for a while longer, but if there’s a decision to

Fellow doctors, sharing this experience with you has been the highest honor ­­

be made about your patient, you want to be part of it. So, you dial the number,

and privilege.

and the person who answers says, “Yes, this is UPMC Quality Control. We have a report of a problem involving one of our patients and would like you to stop by our office immediately.” Your stomach drops. You can’t afford for anything bad to happen, so you rack your brain to figure out which patient and what the problem might be when you hear giggling on the other end of the phone. “Real funny… Thomas.” It’s the standard happy-hour page, the sign that someone has had a rough day and needs to unwind, and you wouldn’t mind a quick glass of “milk” yourself. You roll down to the bar and find the same folks you’ve counted on time and again. You sit around with them for a few hours, letting off steam,

Dr. Conlon, at top left in this family photo, is currently in a combined internal medicine/pediatrics residency program at the University of Pittsburgh Medical Center and Children’s Hospital of Pittsburgh of UPMC. He comes from Chicago and, despite his time here, he’s still “a die-hard White Sox fan.”

RESEARCH Pushing forward with each new discovery

RESEARCH

70 BST3 80 Animal Models 82 Biomedical Graduate Studies 86 Neurobiology 90 University of Pittsburgh Cancer Institute

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BST3

research

A 1 0 - sto ry Re s e ar c h P e r co lato r

ith its open, spacious labs filled with high-tech ­equipment, “plug and play” workstations that can be configured to each researcher’s specifications, and the latest in computing technology, the University’s new Biomedical Science Tower 3 (BST3) is a high-stakes invest­ ment in the vision that inter­disciplinary research is the only way to solve some of medicine’s most ­challenging ­mysteries.

In fact, it is a gleaming, 10-story steel and glass percolator designed specifically

to foster collaborations between clinical researchers like J. Timothy Greenamyre, M.D., Ph.D., director of the Pittsburgh Institute for Neurodegenerative Diseases (PIND), and basic scientists throughout the building in hopes — as any one of them would tell you — of making meaningful advancements to biomedical research and its applicability to improving the human condition. Not only are such collaborations becoming common, they’re also occurring among BST3 colleagues who might not otherwise have ever considered working together. Furthermore, the continuous interplay ­between the work of basic scientists on the lower levels and those on the upper floors who can incorporate these fundamentals into their applied research makes the comparison to a traditional coffee percolator, in which the brewing starts at the bottom and slowly rises to the top to produce the richly desired results, an apt analogy.

“So far, it’s working beautifully,” says Greenamyre, who also is the UPMC

­Professor of Movement Disorders in Neurology. PIND investigates the mechanisms of diseases of the brain in which neurons die or become prematurely impaired, a process known as neurodegeneration. Current therapies can provide temporary relief from the symptoms of these diseases, but nothing has been found to slow or halt them. As the quest for effective remedies continues, one of the connections ­Greenamyre has established is with John S. Lazo, Ph.D., Allegheny Foundation Professor of Pharmacology and director of the University’s new Drug Discovery Institute (DDI), which is located above PIND on the top floor of BST3.

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BST3 Interdisciplinary Interplay “Six degrees of separation” refers to the idea that any two people can be connected by, at most, six other people — demonstrating how small

Drug Discovery Institute (DDI)

DDI has the ability to screen for biologically important compounds and to synthesize completely new ones. It is unusual to have organic chemists and biologists working in such close proximity.

the world really is. The scientific world of BST3 is even smaller, maybe one degree at most. Explore the evolving interdisciplinary research connections percolating through the building by following the arrows. FLOOR 10

John S. Lazo, Ph.D., Allegheny Foundation Professor of Pharmacology and DDI director

Greenamyre is working with Lazo to identify compounds that may be able to protect neurons’ mitochondria from damage, a process that is implicated in most neuro­degenerative diseases.

The DDI can take advantage of the Department of Computational Biology’s computer simulation capability to screen a large library of molecules against a target molecule, thereby reducing the potential candidates by several orders of magnitude.

Zebrafish offer a powerful screening tool for testing biologically important compounds, which may then be optimized by DDI.

FLOOR 9

J. Timothy Greenamyre, M.D., Ph.D., UPMC Professor of Movement Disorders in Neurology and PIND director, and Edward A. Burton, M.B.Ch.B., M.D., D.Phil., assistant professor of neurology and of molecular genetics and biochemistry

FLOOR 8

pittsburgh institute for ­neurodegenerative diseases (PIND)

PIND is dedicated to both clinical treatment and translational research that explores neuro­degenera­tion from a number of perspectives. The goal is to combine the expertise of many investigators and clinicians into potential new therapeutic options. FLOOR 7

FLOOR 6

PIND’s Burton has collaborated with Hukriede to create a zebrafish model of Parkinson’s disease. zebrafish lab

Zebrafish have become a model of choice for many researchers because a number of their genes have human homologues. The small fish also produce large broods, develop rapidly, and have transparent embryos, making them ideal for studying early development. FLOOR 5

Neil A. Hukriede, Ph.D., assistant professor of molecular genetics and biochemistry Ivet Bahar, Ph.D., John K. Vries Professor and chair, Department of Computational Biology

Yeh is working with DDI to fabricate a nanoneedle probe that can be inserted through a cell wall to monitor the cellular target to which a drug binds.

A nanoneedle probe, like that on which Yeh is working, would be particularly attractive to researchers like Greenamyre for monitoring whether potential compounds for neurodegenerative diseases can actually bind to their target neural cell proteins.

FLOOR 4

department of computational biology

The Department of Computational Biology uses in silico screening experiments as a powerful tool for testing the binding affinities of potential drug candidates to target proteins. FLOOR 3

One advantage of using structural and computational biology screening technologies to eliminate dead ends is a higher likelihood of success once the research advances to cell culture and animal studies.

structural biology

FLOOR 2

nuclear Magnetic Resonance (NMR) spectroscopy Screening

The discipline of structural biology applies biophysical methods like NMR spectroscopy, cryo-electron microscopy, and X-ray crystallography to unravel and explain biological phenomena and processes in atomic and molecular detail.

NMR spectroscopy screening is one of the most efficient ways to determine where and how well a molecule binds to a protein, knowledge critical to drug development. FLOOR 1

Joanne Yeh, Ph.D, associate professor of structural biology and nanotechnology researcher

Angela Gronenborn, Ph.D., UPMC Rosalind Franklin Professor and chair, Department of Structural Biology

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The Drug Discovery Institute is home to the Pittsburgh Molecular Libraries

Screening Center, which, as part of a network of facilities recently established by the National Institutes of Health, uses high-tech screening methods to identify small molecules that can be used as research tools in the efforts to learn more about key biological processes involved in human health and disease. PIND is working with the Molecular Libraries Screening Center to look for compounds that may be able to protect mitochondria (sometimes called cellular power sources) from ­damage. “Mitochondrial protein damage caused by oxidative stress — the same chemical reaction that causes iron to rust — is implicated in most neurodegen­er­ ative diseases,” says Greenamyre. “Therefore, we’re looking for compounds that can block this process in mitochondria, particularly in neurons, in the hope they can delay and even prevent the onset of these diseases in susceptible people.”

For PIND, the screening center can test hundreds of thousands of compounds

for their therapeutic potential in a very short time — a capability that, until now, has been limited almost exclusively to pharmaceutical companies. Compounds identified by this type of large-scale screening can be further screened computation­ally and structurally to see how specific their activity is — all without leaving BST3.

A new and extremely power­

ful tool for testing whether compounds have a desired effect is called in silico screening, which employs computers to model how complex molecules behave in the real world. (This analysis is in contrast to in vitro testing of cells or other biological systems in test tubes and in vivo testing in ­animal models.) In silico screening of chemicals is particularly useful for compounds designed to interact with molecules of known three-dimensional structure, says Ivet Bahar, Ph.D., John K. Vries Professor and chair of the Department of Computa­tional Biology, which is housed on the third floor of BST3. “If you have a very large library of molecules that you want to screen against a target molecule, such as an enzyme, you can do it much faster via computer simulations than you could by doing it in the test tube or in cells,” explains Bahar. “If we can reduce the set of potential ­ candidates by one or two orders of magnitude, it’s a major leap ­forward in the ­discovery process.” In addition to being able to predict whether a compound will bind at a particular active site of protein, for example, in silico screening allows computational biologists to suggest which compounds are the most potent inhibitors of a particular enzyme. Bahar’s group has even developed a Web-based tool for biologists to do this online.

Another powerful screening tool available in BST3 that can be used in addition

to or in place of in silico screening is nuclear magnetic resonance (NMR) spectro­ scopy. NMR is one of the most efficient ways of quickly getting structural results and reality checks, says Angela Gronenborn, Ph.D., UPMC Rosalind Franklin

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Hundreds of thousands of compounds can be tested for their therapeutic potential in a very short time and further screened computationally and structurally—all without leaving BST3.

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BST3

research

Professor and chair of the Department of Structural Biology, which was BST3’s first occupant when it opened in September 2005. “When we do NMR, we see a resonance for each amino acid of a protein. So, we can see very quickly how well a particular molecule binds to a protein and where it binds,” she explains. Before NMR was widely available, drug development was much more of an art than a ­science and led to many dead ends.

A well-known example of this process was the development of early drugs to

treat sickle cell disease, which is caused by the aggregation, or clumping, of hemoglobin molecules in red blood cells. The first anti-sickling drugs were designed to bind to a specific site on each hemoglobin molecule to prevent them from clumping. However, once the drug developers were able to examine these drugs structurally, they found that the agents did not bind to their intended target but, rather, at another location on the hemoglobin molecule. “These days, it’s ­usually a good idea to check structurally whether a molecule can actually bind where you want it to before putting it through any kind of trial,” says Gronenborn.

One advantage of using such sophisticated screening technologies is a higher

likelihood of success in cell culture and animal studies, which means less waste of these valuable resources. At PIND, for example, promising molecules that can ­protect mitochon­drial pro­teins from oxidative damage based on a number of criteria will be tested in zebra­fish that have been gene­tically engineered to display symptoms similar to Parkinson’s disease (PD), a progressively debilitating neuro­logical disease that causes loss of nerve cell function in the part of the brain control-

BST3 houses one of the largest zebrafish colonies in the world, with more than 10,000 separate tanks.

ling muscle movement. As many as 1.5 million Americans have this disease. “My colleague Ed Burton has developed zebrafish in which genes that code for the mutated PD proteins in humans have been inserted into the fish,” says Greenamyre. “Not only do the fish display many of the movement problems seen in people with PD, but they also show patho­ logical and biochemical abnormalities reflecting those seen in the human ­disease. We should, therefore, be able to rapidly determine which ­compounds have protec­ tive effects.”

Zebrafish, in fact, represent another powerful BST3 screening tool for testing

biologically important compounds. Because zebrafish have many genes that are similar in sequence and are expressed at comparable stages of development as human genes, they have become models of choice for many researchers. Further­ more, zebrafish produce large broods, breed all year, are easily maintained, develop rapidly, and have transparent embryos. Therefore, they are particularly useful for directly observing the morphological effects of genetic mutations on development. BST3 houses one of the largest zebrafish colonies in the world, with more than 10,000 separate tanks.

Compounds that pass the zebrafish test may eventually percolate back up to

Lazo and the Drug Discovery Institute, which has the ability not only to screen for

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biologically important compounds but also to synthesize completely new ones as well. So, if the screens come up with compounds that have most but not all of the

Developing Vaccines for Difficult Diseases

desired characteristics, DDI researchers, who come from the Departments of Pharmacology, Chemistry (School of Arts and Sciences), and Pharmaceutical Sciences (School of Pharmacy), have the capability of altering them to fit their exact needs. Furthermore, the institute has the largest collection of fume hoods —  a critical tool for organic chemists who want to ­synthesize new or alter existing compounds — on campus. “Our situation isn’t unprecedented, but it certainly isn’t the norm,” says Lazo, who chaired the Depart­ment of Pharmacology for 17 years before heading DDI. “For example, it’s very unusual to have organic chemists and biologists working on the same floor, much less in the same building. At Yale, my former institution, the chemistry department was more than a mile away, so collabo­ra­tions were always difficult.”

Although it will take many more months, and perhaps years, to determine how

successful such collaborations will be in finding new therapies to treat diseases, there is little doubt that they open up new and exciting avenues of research. For example, Joanne Yeh, Ph.D., associate professor of structural biology and a nanotechnology researcher, is discussing with Lazo’s group the development of a probe that can monitor where a drug goes after it enters a cell. Her group is attempting to fabricate a nano­needle that can be inserted through a cell wall to monitor the specific target in the cell to which a drug binds. Such a probe would be particularly attractive to researchers like Greenamyre for monitoring whether potential com­ pounds for neurodegenerative diseases can actually bind to mitochondrial proteins in a neural cell. Greenamyre, for one, can’t wait for this and other ­collaborative ventures in BST3 to come to fruition. “I feel very fortunate to be able to come to work every day in this building,” he says. “It really is a unique place to do research, and I’m confident that it will soon start paying dividends for the patients we’re ­trying to help.”

Researchers at the University’s new Center for Vaccine Research (CVR) in BST3 are ready to scrabble. They’re prepared to battle a range of diseases from emerging ones, like avian ­influenza, to older scourges like HIV and tuber­cu­losis, to human-modified diseases that could be used for bio­ terrorism. With so many dangerous infectious agents, which vaccines does the center tackle first? “Our ongoing focus will be threefold—flaviviruses (like dengue fever), influenzas, and tuber­culosis. We’ll also be working on various platforms that can be used for other viral systems and on the assessment of vaccine immunity,” says Ronald C. Montelaro, Ph.D., associate director of the center and professor of molecular genetics and biochemistry. With initial funding from the National Institutes of Health and the Department of Defense, the CVR is closely aligned with the Regional Biocontainment Laboratory, one of 13 dedicated facilities across the country with specialized capabilities that allow investigators to conduct essential bio­defense research into potentially deadly infectious agents under safe, contained, and highly controlled conditions. Faculty members from several School of Medicine departments, including Molecular Genetics and Biochemistry, Immunology, and Pediatrics, the Department of Medicine’s Division of Infectious Diseases, and the Department of Infectious Diseases and Microbiology in the Graduate School of Public Health will conduct research at the center. Headed by a leading expert in the field of infectious diseases, Donald S. Burke, M.D., who is also dean of the Graduate School of Public Health, associate vice chancellor for global health, and UPMC Jonas Salk Professor of Global Health, the center’s initiatives will include basic

research

research, preclinical and clinical trials, and corporate partnerships to make vaccines (although, at some point in the future, the center may build a commercial vaccine operation). While the task of developing vaccines for notoriously difficult diseases is daunting enough, researchers will also be dealing with the variability of viruses, their potential to change over time, and with learning how to recognize different viral strains. “I use the example of cold and polio viruses,” says Montelaro. “They look the same under the microscope. There are three strains of polio, and we have a vaccine that guards against all three strains; but there are 130 to 140 strains of the common cold virus, and it’s difficult to develop a vaccine for all of them.” CVR researchers will have to first recognize different strains of viruses by making extensive surveys of them worldwide and determining how they evolve; then they’ll examine the strains, arrive at consensus strains, and evaluate those for a vaccine. Burke is known for his hands-on, global approach to vaccine research and wants the CVR to have relationships with other countries where some of these diseases are found naturally. “We must study these diseases in nature and in animals so that we can understand how the viruses emerged in the first place,” he says. “AIDS, SARS, and influenza viruses jumped from animals to humans; and we don’t have a good handle on how that adaptation occurs.” Montelaro and Burke are still recruiting faculty members to the center and realize that it may be a while before the center is scientifically productive. “I know how hard it is to make a real vaccine,” says Burke. “I was involved with the successful development and testing of the hepatitis A and Japanese encephalitis vaccines, and it’s wonderful to see it through — from the beginning to the end. Being able to cause diseases to disappear is a real motivator.”

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ANIMAL MODELS

Drosophila melanogaster (pictured above), more commonly known as the fruit fly, is one of the most widely used animal models in scientific research. More than half of the fly’s protein sequences have known mammalian analogues, a percentage that is rapidly increasing as more and more genomes are mapped. “Another reason flies are exceptional models is because of the way their short lifespans scale against the longer span of a mammal,” says Michael J. Palladino, Ph.D., assistant professor of pharmacology. “A fly can be normal for the

first five or six days of its life and then rapidly progress to a disease state that might take 18 months or more to simulate in a mouse model.” This time scaling also applies proportionately to human conditions, making all Drosophila particularly useful in the study of the onset and development of neurodegenerative and other progressive diseases that often take 40 to 60 years to appear.

The Xenopus laevis is a small African clawed frog that produces a very large egg. Before X. laevis eggs begin division, they exist as single cells called oocytes (pictured right), which at 1.3 mm are actually visible to the naked eye. (In comparison, a human oocyte is considered large for a single cell at 0.1 mm.) When fertilized, the X. laevis egg develops so rapidly that a general body plan for the resulting embryo is evident within 24 hours. The embryo can also be cultured in vitro and microsurgically manipulated, making it an excellent model for

identifying and characterizing early developmental processes. X. laevis is being used at Pitt to study plasma membrane transport issues that may be applicable to different types of cells. Neil A. Hukriede, Ph.D., assistant professor of molecular genetics and biochemistry, also uses the frog embryos as models “to identify the earliest cells that give rise to the kidney and to understand the molecular events that lead to kidney development.”

It might be a surprise that the genome of an ordinary-looking worm is 40 percent homologous to the human genome, but that commonality, along with the worm’s low cost, easy maintenance, and ability to revive after being frozen, makes Caenorhabditis elegans (pictured below) a versatile tool with which to address a variety of developmental and pathological questions. “The vast complexity of the vertebrate nervous system makes it difficult to study some neurological disease processes,” says Miguel Estevez, M.D., Ph.D., assistant professor of neurology, who uses C. elegans to study the regulation of serotonin levels. “We can circumvent those complexities by using an organism that is much simpler but has many of the same signaling mechanisms.”

Danio rerio (pictured above), the zebrafish, is not only a common aquarium fish but also an ideal small vertebrate genetic screening model for a number of human characteristics and developmental processes. At the School of Medicine, zebrafish

are used as models to answer research questions about the digestive system, kidneys, and nervous system. “Multicellular organisms arrange cells in special patterns to form distinct structures,” says Xiangyun Wei, Ph.D., assistant professor of

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ophthalmology, “but we don’t fully understand the instructions that direct the formation of these patterns.” Wei studies the zebrafish retina in order to better elucidate the molecular mechanisms that underlie neural and retinal development.

Model Subjects ALL LIVING THINGS ARE ORGANIZED BY THE GENETIC INFORMATION ENCODED IN THEIR DNA. AS NEW SPECIES ADAPT AND EVOLVE, GENES AND GENE SEQUENCES THAT PROVE EFFECTIVE FOR FUNDAMENTAL PHYSIOLOGICAL DEVELOPMENT AND FUNCTIONS ARE HELD OVER, OR “CONSERVED,” FROM OTHER SPECIES. BECAUSE OF THESE GENETIC HOMOLOGUES AND ANALOGUES, SCIENTISTS CAN GAIN VALUABLE INSIGHT INTO THE HUMAN CONDITION BY STUDYING THE CREATURES SHOWN HERE, WHICH REPRESENT JUST SOME OF THE RESEARCH MODELS BEING EXPLORED AT THE SCHOOL OF MEDICINE.

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B I O M E D I C A L G R A D U AT E S T U D I E S

BIOMEDICAL GRADUATE STUDIES: A PROGRAMMATIC APPROACH

U

ntil the mid-1990s, graduate education at most medical schools, including Pitt, was departmentally organized. Although this approach is logical from an administrative perspective, it fails to exploit the rapid pace of change that characterizes biomedical science. As a way of both responding to and propelling this change,

the School of Medicine designed and implemented the Interdisciplinary Biomedical Graduate Program (IBGP), which features a core curriculum the first year followed by the opportunity to pursue research and dissertation work in one of seven interdisciplinary areas: biochemistry and molecular genetics, cell biology and molecular physiology, cellular and molecular pathology, immunology, molecular pharmacology, molecular virology and microbiology, and neuroscience. This level of flexibility accommodates students whose research interests are still evolving by introducing them to a variety of fields through interdisciplinary courses and laboratory experiences. It also encourages the rapid development of new programs for more focused students as new areas of science come to the forefront. The School of Medicine’s three newest graduate programs are Molecular Biophysics and Structural Biology, the Joint Program in Computational Biology, and the Program in Integrative Molecular Biology. John P. Horn, Ph.D., associate dean for graduate studies and IBGP director, is a strong advocate of a programmatic approach to graduate education. Horn, also a professor of neurobiology, is himself an accomplished scientist who studies synaptic regulation of information processing in the neural circuits. His understanding of the flow of neurological information is echoed in his understanding of the flow of scientific knowledge in the School of Medicine. In the course of their training, graduate students are encouraged to move freely among departments for the most comprehensive education on their topic. Even if they are ultimately destined for a career at the lab bench, IBGP students are encouraged to think in terms of clinical problem solving. “With a programmatic, rather than departmental, approach,” he says, “graduate students have facilitated development of research projects within clinical departments.” Horn believes that by encouraging graduate students to move freely from department to department and from bench research to clinical study, both the school and the students reap the benefits. “A programmatic approach allows the graduate students to further strengthen the connection between science and medicine,” he says. “Our goal is to train these people, not just in terms of their own research but to look at the larger picture. We want to educate them about the past, but we also want to prepare them for the future.”

RESEARCH

MOLECULAR

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BIOLOGY I n fall 2006, five students became the first to enter the Program in Integrative Molecular Biology (PIMB), a joint graduate program created by the School of Medicine and the Department of Biological Sciences in the School of Arts and Sciences to appeal to students with a strong interest in the structure and function of molecules that comprise living systems. “We wanted to develop a novel, cross-campus training program to recruit outstanding graduate students to study molecular biology at the University,” says Gerard L. Apodaca, Ph.D., program director and professor of medicine and of cell biology and physiology. The PIMB curriculum is designed to rapidly immerse students into a research environment and provide mentorship as they develop into independent scientific practitioners. “Having research experience as both an undergraduate and graduate student, I wanted to hit the ground running in pursuit of a doctorate,” says PIMB student Eric de Groh. “The accelerated nature of PIMB has allowed me to do that.” The goal of the four-year program is to produce scientists who are skilled not only in the art of technical execution but also in the creative thinking required to address important questions in

molecular biology. Students may choose between two main areas of focus. The genomics, proteomics, and gene function area takes advantage of the many recent advances in genomic sequencing, gene production, and protein folding. The second area of focus, cellular and developmental dynamics, utilizes technological developments to better understand the dynamics of cell function and interaction and how those interactions lead to organism development. “Students coming into the program already know what it takes to be a scientist and have the opportunity to produce meaningful research from day one,” says PIMB faculty member Judith Klein-Seetharaman, Ph.D. As assistant professor of structural biology, of pharmacology, and of computational biology at the School of Medicine and as a research scientist for the Language Technologies Institute at Carnegie Mellon University, Klein-Seetharaman knows what it takes to generate high-quality work in a multidisciplinary environment. “The PIMB program is designed to produce scientists who can examine a question by addressing the science at every scale, from molecular to macroscopic,” she says. “The PIMB graduate will be a builder of bridges.”

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B I O M E D I C A L G R A D U AT E S T U D I E S

M

olecular Biophysics and Structural Biology (MBSB) is an interdisciplinary doctoral program that explores the intersections of physics, chemistry, biology, and medicine. This program brings together faculty from the School of Medicine, the School of Arts and Sciences, and Carnegie Mellon University to concentrate on fundamental scientific principles that form the basis of the molecular reactions and interactions in biological systems. Advances in biophysical techniques and developments that allow more sophisticated imaging — increasingly powerful electron microscopes, magnets, and computers, for example — have opened the door to a vast array of new possibilities. Scientists are now able to analyze the structure and movement of molecules with unprecedented accuracy and precision. “For a long time, people have thought of the activities within a cell primarily as a series of chemical interactions. Now, more and more people are thinking in structural terms as well,” says MBSB student Matt Fagerburg. “We’re starting to look at molecules as three-dimensional machines, as dynamic agents with structures that both affect and respond to what’s happening around them.” Fagerburg, who is studying the development and use of single-molecule techniques to investigate DNA-protein structures, says the greatest strength

of the MBSB program is its faculty, “an amazing array of people” whose diverse interests offer students a great deal of flexibility as they develop their research emphases. While common core courses provide a solid grounding in molecular biophysics and biomedical sciences, research rotations in the first year offer students the opportunity to focus their scientific interests. They are then free to select one of seven focal areas of research: macromolecular recognition; virus, lipid, and protein structure and interactions; principles of protein structure and dynamics; membrane proteins; gene regulation and signaling; cellular biophysics; or chemical structure and dynamics. MBSB Director Angela M. Gronenborn, Ph.D., UPMC Rosalind Franklin Professor and chair of the Department of Structural Biology, says the program opens up a place in the School of Medicine for researchers with less traditional but increasingly important skill sets. “Students who come from more quantitative sciences — physics, chemistry, math — and want to apply those skills in biomedical areas can now do so. I strongly believe that the next generation of scientists will need to be much more versatile in their backgrounds,” says Gronenborn, “and that the development of this multidisciplinary program reflects the integrative movements of science in general.”

STRUCTURAL

BIOLOGY

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COMPUTATIONAL

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BIOLOGY T he Joint Program in Computational Biology (JPCB) offered by the University of Pittsburgh and Carnegie Mellon University began enrolling students in fall 2005. The development of this program was sponsored by a $1 million grant, one of only 10 such grants awarded nationally, from the Howard Hughes Medical Institute. Building on Pittsburgh’s strong history of achievement and progress in both the computational and biological sciences, the JPCB is designed to prepare scientists to harness the constantly expanding power of highlevel computing and apply it to the fundamental principles of the life and physical sciences. Students learn and design computer-based modeling and simulation techniques that allow an unprecedented level of exploration of the structure and function of cells and molecules. Computational algorithms can save countless lab hours by running virtual scenarios that whittle down massive lists of variables for complex dynamics like DNA site binding and protein folding. “Not only will our doctoral students have the opportunity to take advanced courses at both universities,” says Program Director Ivet Bahar, Ph.D., John K. Vries Professor and chair of the Department of Computational Biology,

“but they also will work side by side with leading computational biologists and their clinical and basic research collaborators on solving complex problems in biological sciences or identifying more rational approaches to the development of new drug targets.” The JPCB curriculum includes a set of core courses that provide students with a common background in the concepts and methods of computational biology. The program also offers five areas of specialization: computational genomics, computational structural biology, cellular and systems modeling, bioimage informatics, and computational neurobiology. These choices encompass a wide range of research topics, from molecular modeling and protein dynamics to large-scale analysis of genome and proteome data. One of the ultimate goals of the program is to train researchers to use computation not only as a tool but also as the platform for a fresh way of approaching science. “It’s not just about adding a quantitative element to traditional biology,” says Ivan Maly, Ph.D., assistant professor of computational biology. “It’s about asking new questions.”

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THE HUMAN BRAIN IS NOT ONLY, AS SOMETIMES QUOTED, “A MOST UNUSUAL INSTRUMENT OF ELEGANT AND AS YET UNKNOWN CAPACITY,” BUT ALSO A SUBJECT OF INTENSIVE RESEARCH AT THE SCHOOL OF MEDICINE, AS EVIDENCED BY THESE HIGHLIGHTS, WHICH REPRESENT JUST SOME OF THE STUDIES BEING DONE HERE IN THIS FIELD OF ENDLESS FASCINATION.

NEUROBIOLOGY

RESEARCH

H O N I N G S K I L L E D S E Q U E N T I A L M OV E M E N TS

Remember how your mother would always remind you not to skip piano practice? “Practice makes perfect,” she’d say. She was right, of course, and Peter L. Strick, Ph.D., knows why. In a recent article in the Journal of Neurophysiology, he and colleagues provide evidence that long-term practice of a sequence of movements (like a piano arpeggio) sculpts the response properties of neurons in the primary motor cortex (M1) and enhances the consolidation and retention of the acquired skill. “In the past, M1 has been thought to be involved in the simple generation of motor output. Our results suggest that M1 is a possible site for the storage of the internal representation of skilled sequential movements,” says Strick, professor of neurobiology and psychiatry as well as co-director of the Center for the Neural Basis of Cognition (CNBC). This finding is just one of many in Strick’s studies of the brain. He recently showed that premotor areas of the frontal cortex — once thought to influence motor function only through connection to the primary motor cortex — link with spinal motor neurons and may be responsible for some direct generation and control of voluntary movement. And he found that the cerebellum—formerly thought to be the seat of movement, coordination, and balance — is also a player in the thinking process. To top it off, he demonstrated that the cerebellum may control functional aspects of the basal ganglia, a region of the nervous system that has long been associated with Parkinson’s disease, Huntington’s disease, and addiction.

TA M I N G S C H I Z O P H R E N I A

Arrow indicates cortical GABA neuron

Using drugs to control the symptoms of people with schizophrenia is nothing new. However, David A. Lewis, M.D., UPMC Professor of Translational Neuroscience, is developing a drug that may restore properly functioning thought processes. Instead of controlling the delusions and hallucinations associated with schizophrenia, the drug may help to lessen cognitive defects like dysfunction of working memory that are associated with the disease. People with schizophrenia have neurons that don’t produce enough gamma-aminobutyric acid (GABA). The drug acts on a class of neurons in GABA that regulate working memory. Lewis thinks the drug will “boost GABA signaling just at the location where the signaling is deficient and not boost it at locations where things seem to be normal.” He hopes that the drug, along with antipsychotic medications and cognitive and social rehabilitation, will help enhance cognitive capacity and, thereby, help people reintegrate into society. His greater hope is that the drug could be used to treat young people with early stages of the disease and reduce the severity of its symptoms.

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RESEARCH

RESPONDING TO EMOTIONAL STIMULI

MECHANISMS OF MEMORY AND LEARNING

Guo-Qiang Bi, Ph.D.

Timing is everything when it comes to learning and memory — or, more particularly, when it comes to the chemical synaptic interactions between neurons that lead to learning and memory. As a postdoc at the University of California, San Diego in 1998, two years before coming to Pitt, Guo-Qiang Bi, Ph.D., clarified and expounded upon the previous work of others and found that for a synaptic connection between two neurons to be strengthened — that is, for learning to take place — the first neuron must fire within about 10 milliseconds of the second, or nothing happens to the synapse. If the second neuron fires before the first, the synapse weakens. His resulting paper, later described as a classic, led to a precise understanding of the time factor involved in making memories. Now, as a member of Pitt’s Department of Neurobiology and of the CNBC, Bi studies ever-changing networks of multiple neurons grown in culture dishes that exhibit persistent reverberatory activity that may represent a mechanism for short-term memory in the brain. “It’s really hard to study the nature of persistent activity in vivo,” Bi says. “There are too many cells in a very complex environment; but in vitro, we can monitor and manipulate the activity of many neurons in a small network and probe the essential mechanisms.” Still, his groundwork, which he hopes will someday lead to a complete set of rules regarding the behavior of neural networks, holds important implications for understanding broad aspects of brain development and activity in addition to the mechanisms of memory and learning.

“It’s really hard to study the nature of persistent activity in vivo . . . but in vitro, we can monitor and manipulate the activity of many neurons in a small network and probe the essential mechanisms.”

Looking at a scared face causes the amygdala, the brain’s so-called hub of fear, to light up on an fMRI scan much more in someone with a short variant of the serotonin transporter gene than in someone with the long variant.

By studying the amygdala, an almond-sized region of the brain linked to fear and emotion, Ahmad Hariri, Ph.D., assistant professor of psychiatry and a CNBC member, has shown that some people’s brains have a genetic tendency to react strongly to emotional stimuli. He and colleagues looked at a variant of the human serotonin transporter gene, long suspected of having a link to anxiety. Using functional magnetic resonance imaging (fMRI) of the brain, they found that people with one or two copies of the short version of the variant, as compared with those having two copies of the long version of the variant, tended to show much greater amygdala activity when they viewed pictures of scared faces. “It’s like taking a hammer and smacking the amygdala, getting it to reverberate, and then measuring those reverberations and understanding what factors determine the magnitude of those reverberations,” says Hariri, whose research focuses on the interconnections of genes, brain function, and behavior. He and colleagues subsequently found that the gene variant also biased communication between the amygdala and the prefrontal cortex — a process that shapes behavior and predicts the degree to which healthy humans are harm-avoidant.

A S I M U LTA N E O U S S U R P R I S E

Sure the brain is mysterious, but neuroscientists thought they had at least this much figured out: Some neurons release excitatory neurotransmitters, which help neurons propagate impulses, and some release inhibitory neurotransmitters, which dampen impulses. It’s one or the other, right? Well, apparently not always. Researchers in the lab of Karl Kandler, Ph.D., associate professor of otolaryngology, were surprised to discover neurons during brain development that simultaneously release not only the inhibitory transmitters GABA and glycine but also — and here’s the surprise — glutamate, the classic excitatory transmitter that is involved in learning and memory, addiction, chronic pain, epilepsy, and other conditions. This finding, which Kandler admits seems to contradict fundamental principles of neuroscience, “sheds new light on how inhibitory synapses evolve and are assembled into functional circuits in the developing brain.” Such research might someday explain the biological cause of brain disorders like epilepsy, schizophrenia, and tinnitus, which involve deficits that prevent normal inhibition of cells. In the meantime, the finding was the lead article in the March 2005 issue of Nature Neuroscience. Top: Close-up of a synaptic contact where both stimulating and calming neurotransmitters might be found. Bottom: Unexpected glutamate activity in the part of the brain called the LSO. (The color labels a protein that enables glutamate release.)

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DREAM TO REALITY: THE COMING OF A WORLD-CLASS CANCER INSTITUTE

“E

mbarrassing” is how Thomas Detre, M.D., describes the landscape for cancer care in Pittsburgh in the mid-1980s — and he would know. In 1984, Detre became Pitt’s senior vice chancellor for the health sciences, with responsibility for the University’s six health sciences schools, including the School of Medicine. As such, he also became an unofficial “go-to” person for medical advice or

referrals. “I’ve never adopted the parochial attitude that we’re the best in everything,” says Detre, now a distinguished service professor of psychiatry. “When people would ask me where I thought they would receive the best care, I sent them wherever I thought was the best place possible.” Although Pitt was making great strides at the time in many areas of medicine, for cancer care, the best place to go was usually somewhere else. (The notable exception was pioneering work in breast cancer being done by Bernard Fisher, M.D., who ultimately changed the treatment protocol for the disease and even established a regimen for prevention.) Overall, however, the University was “very thin” in terms of cancer expertise, Detre recalls. Consequently, cancer patients and their families often found it better to travel to Cleveland, Philadelphia, New York, or Washington, D.C., for treatment. The fact that the University of Pittsburgh Cancer Institute (UPCI) today ranks among the foremost cancer centers in the United States is a testament to how much things have changed in the past 20-some years — as well as to the determination of one man: Ronald B. Herberman, M.D., founding director of UPCI, associate vice chancellor for cancer research at Pitt, Hillman Professor of Oncology, and director of the UPMC Cancer Centers. Ronald B. Herberman, M.D.

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Detre dreamed of one day making Pittsburgh a center of excellence for cancer research and treatment, and he largely credits Herberman with making that dream RESEARCH HIGHLIGHTS

a reality. “I’ve heard people say that Ron Herberman is made of steel, but I tell everyone he’s really made of titanium. …He’s one of the most persistent people I’ve ever met,” Detre says. That’s high praise, especially from Detre, who bears his own reputation for persistence. In fact, if not for Detre’s dogged efforts to find just the right person to lead Pitt’s cancer center, Herberman might not have come in the first place, and UPCI might be nowhere near the world-class cancer institute it is today. In January 1984, a University task force concluded that a consortium consisting of Pitt, its affiliated hospitals, and Carnegie Mellon University should work together

■ Ovarian cancer treatment is hampered by a lack of

sensitive screening assays that can identify individuals at early stages when treatment is most effective. Anna Lokshin, Ph.D., has developed a panel of protein markers and a multiplex assay that can predict ovarian cancer risk with high sensitivity and specificity. Her studies provide great promise for development of an accurate, specific, and convenient serum-based diagnostic test.

to establish a regional cancer institute; all of the parties agreed to provide start-up revenue. As luck would have it, not long after assuming his new role as senior vice chancellor for the health sciences, Detre attended a Richard King Mellon Foundation dinner and gave a talk about the future of cancer care. That talk led to a $3 million grant from the foundation to help establish the cancer institute. With initial funding in hand, Detre appointed a search committee to find a director, but viable candidates were reluctant about Pittsburgh, which still bore the scars of a smoky steel town whose heyday had passed. Eventually, the committee found a well-respected expert in chemotherapy who agreed to an interview. However, as Detre recalls, the candidate “would not do.” He wanted someone more in tune with newer, more innovative cancer therapies, someone who could effectively lead the institute into the future. Eminent oncologists and researchers — one of whom later won a Nobel Prize — were assembled to identify the credentials such a candidate should have. Like Detre, his advisors believed that molecularly targeted cancer treatments would likely come to the forefront and that much could be learned about cancer by better understanding the body’s immune system, why it sometimes fails, and how it can be strengthened when it does. Gerald S. Levey, M.D., head of the search committee and chair of the Department of Medicine at the time, knew someone who fit that description perfectly. It was Herberman, who had begun a long and notable career at the National Cancer Institute in 1966, two years after earning his M.D. from New York University. Levey and Herberman had been friends since their days as residents at Massachusetts General Hospital. From the outset of Herberman’s career, immunology was the focus of his work. In the early 1970s, Herberman’s laboratory discovered that a new type of immune cell, called a natural killer cell, could attack cancerous tumors, and he demonstrated its importance in resisting the spread of cancer. Based on evidence that some people develop a natural immunity to cancer, his lab also organized a national program for improving cancer diagnosis based on immune markers, a field now known as immunodiagnosis. Likewise, it developed a novel diagnostic tool by detecting biochemical markers in the blood, urine, and tissues of people with cancer. Herberman played a major role in establishing NCI’s Biological Response Modifiers Program, which funded research on biological and immunological cancer treatments

■ Andrew Lepisto, Ph.D., and Olivera J. Finn, Ph.D.,

have developed a therapeutic vaccine for pancreatic cancer that combines synthetic MUC1, a tumor-associated protein found in pancreatic tumor cells, with a patient’s own dendritic cells, which contribute to the attack against tumor cells. In clinical trials, the vaccine produced an immediate active immune response in all patients and showed continued immune presence and disease suppression three years post-vaccination in one-third of patients treated. Continued improvements should produce a much-needed therapeutic alternative for this particularly aggressive cancer.

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like immune messenger molecules, vaccines, gene therapy, and bone marrow transplants. However, when contacted about the Pittsburgh job, Herberman, like the RESEARCH HIGHLIGHTS

others, was reluctant about it.

■ Beth R. Pflug, Ph.D., is developing an assay that uses

[ 11 C] acetate to target fatty acid synthase and improve positron emission tomography (PET) imaging in prostate cancer. Modulation of fatty acid synthase activity with known pharmacological pathway inhibitors may improve [11 C] acetate imaging, which has already shown promise for prostate cancer imaging, particularly in detecting local recurrence.

“The reaction I got from my colleagues at NCI was that I shouldn’t even bother going to Pittsburgh because there wasn’t much going on in cancer at the time. In addition, the hospitals were too independent and weren’t under control of the University. The general consensus was that it would probably be too much trouble, and it probably would fail,” Herberman recalls. Only after considerable armtwisting did he agree to an interview. Herberman had been to Pittsburgh only once before, and it was a quick trip — no sightseeing. This time, he was surprised to find the city so attractive. However, he remained skeptical about the opportunity. Detre listened patiently to his concerns,

■ Satdarshan P.S. Monga, M.B.B.S., and colleagues

assured him they were solvable, and suggested he ask around for input from others.

have developed the first targeted therapy for liver cancer using cell cultures of hepatocellular cancer (HCC). Platelet-derived growth factor receptor-alpha (PDGFRα) is expressed in HCC cells and exhibits high levels in early stages of the disease. The investigators designed a monoclonal antibody to target PDGFRα and found that it decreased tumor cell proliferation and increased tumor cell death. Currently, most HCC patients live only a short time after diagnosis, demonstrating the importance of this finding for liver cancer patients. In addition, PDGFRα is expressed in various other malignancies, including brain tumors, prostate tumors, gastrointestinal tumors, leukemia, ovarian cancer, and skin cancers, suggesting the possibility of broad therapeutic applications.

Herberman did and found that Detre was known as a man of his word — and more. Previously, under Detre’s leadership, Western Psychiatric Institute and Clinic had secured tens of millions of dollars in clinical research grants, established three National Institute of Mental Health centers of excellence, recruited top-level researchers and clinicians, and emerged as a research powerhouse with a wealth of groundbreaking studies on topics ranging from psychopharmacology to neurobiology and the genetics of mental disorders. Herberman was also impressed by the collection of University-affiliated hospitals, which subsequently formed the core of the University of Pittsburgh Medical Center (UPMC). At NCI, his access to cancer patients was limited; he saw the setup in Pittsburgh as much more feasible for the kinds of studies he wanted to conduct. Herberman finally agreed to take the job. In September 1985, the fledgling cancer institute consisted of Herberman, a secretary, and a three-room suite in the former Eye and Ear Hospital that had been converted into offices. Barbara Duffy Stewart soon joined UPCI as one of its first employees. She recalls that on her first day on the job, while helping unpack a pile of boxes shipped from NCI, Herberman never removed the jacket of his corduroy suit despite the sweltering heat. It was a telling sign, because throughout the early frantic days of the institute, Herberman never lost his cool, says Duffy Stewart, who is now executive director of the American Association of Cancer Institutes. “Thank goodness for his personality. When something unexpected would happen, and the rest of us would go crazy, he was able to keep everyone on an even keel.” Not long after Herberman arrived, John Kirkwood, M.D., a highly regarded melanoma researcher from Yale, was recruited as UPCI’s clinical director. Another early recruit was Theresa Whiteside, Ph.D., who was already at Pitt in the Department of Pathology. “Ron wanted me to start an immunological monitoring laboratory for the cancer institute very similar to the one I ran for the Department of Pathology; however, this would be for monitoring patients’ immune responses to cancer therapy,” she recalls. With Kirkwood and Whiteside on board, Herberman began aggressively recruiting more basic scientists and physicians. Places Rated Almanac had recently named Pittsburgh as America’s Most Livable City for the first time (an accolade

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repeated in 2007), and he used this distinction as leverage to convince potential recruits to come and see what the city and its new cancer center had to offer. Come RESEARCH HIGHLIGHTS

they did, few at first but many more before long, and Herberman’s concerns grew about the availability of space and resources to support them. In 1986, the Mellon Foundation donated another $3 million, followed by $8 million in 1989 to have two floors of the University’s new Biomedical Science Tower (BST) devoted to cancer research. In addition, a core grant from NCI in 1988 was used almost exclusively to develop infrastructure and to build shared facilities for the institute’s research faculty. Nevertheless, for UPCI to become a leading cancer center, the quest for additional funding and space had really just begun.

■ Early-stage breast cancer in postmenopausal women

is often treated with a hormone-based chemotherapy, like letrozole, but this therapeutic approach is known to decrease bone mineral density, thus increasing fracture risk. Adam M. Brufsky, M.D., Ph.D., has found that if patients receive zoledronic acid prior to chemotherapy, bone loss in the lumbar spine is prevented.

In 1990, after only five years, UPCI won a powerful endorsement with its designation by NCI as a comprehensive cancer center — “the youngest center ever to receive that distinction,” Herberman says — in recognition of its far-reaching strengths in cancer treatment, research, education, and prevention. UPCI today is one of only 39 comprehensive cancer centers in the country and the only one in western Pennsylvania. Throughout the 1990s, while UPCI increasingly incorporated faculty from both Pitt and Carnegie Mellon into its research projects, it was basically an “invisible” cancer institute, with clinicians and researchers scattered around the campuses of both universities. What the institute needed more than anything was a real home. That opportunity came in 1997 when UPMC wanted to acquire Shadyside Hospital. One condition mandated by the hospital’s Board of Trustees for the merger was that UPMC establish a center of excellence there. Consideration was given to centers in cardiovascular disease and cancer, but since Shadyside already had a robust cardiovascular program, a cancer center was the logical choice. Although Herberman was intrigued by the prospect of relocating UPCI’s inpatient program to Shadyside, he didn’t want to leave the outpatient and research activities in Oakland because that would fragment the institute even more. So, before agreeing to the move, he wanted a commitment for a new outpatient facility and space for the institute’s research labs. UPMC initially bristled at the idea; “shocked” is how Herberman describes the reaction he got. Disappointed but determined, he set out to build a case for more space. In his capacity at the time as Pitt’s associate vice chancellor for research, health sciences, Herberman had access to data showing that, contrary to perceptions, lab space at the University was quite tight and would be getting tighter. Building lab space at Shadyside would not only allow UPCI to move all of its personnel to one location but also free up two floors of space in BST for other ventures. Finally convinced, UPMC announced plans in 1998 for the cancer center’s new facility to be built adjacent to Shadyside Hospital and launched a capital campaign to fund it. Pittsburgh philanthropists Henry and Elsie Hillman provided the lead $10 million for the project and a name for the building: the Hillman Cancer Center, which today serves as home of UPCI as well as the flagship of the UPMC Cancer Centers, a network of 45 clinical care facilities in western Pennsylvania and the surrounding region. The $130 million complex with more than 350,000 square feet of research

■ Lisa H. Butterfield, Ph.D., and John M. Kirkwood, M.D.,

are testing a new combination immunotherapy vaccine in melanoma patients. This immunotherapy, which builds on previous work, is expected to enhance outcomes because it first triggers immune activation with a tumor-specific vaccine and subsequently “boosts” the effect with interferon alpha treatments, resulting in a more potent therapy.

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and clinical space opened in 2002. An adjacent facility, the UPMC Cancer Pavilion, houses administrative offices and a 400-seat auditorium. RESEARCH HIGHLIGHTS

In 2005, the Hillmans gave $20 million more — the largest single gift ever to Pitt

■ Theresa Whiteside, Ph.D.; Robert L. Ferris, M.D., Ph.D.;

Albert B. DeLeo, Ph.D.; and colleagues have identified a specific p53 protein mutation present in more than 12 percent of patients with a particular form of squamous cell carcinoma of the head and neck. This peptide can induce tumor recognition in immune cells, suggesting that vaccines targeting the mutation could trigger robust antitumor immune responses. In addition, loss of p53 protein function is common across many cancers, suggesting that p53-specific vaccine development could provide a therapeutic option for other cancer types.

and UPMC — to create the Hillman Fellows Program for Innovative Cancer Research, which provides seed money to stimulate collaborative and novel cancer research, and to launch a major, five-year initiative to raise $200 million for UPCI’s future growth and development. With the Hillman Cancer Center at capacity, attention has turned to the prospect of expanding UPCI’s facilities so that recruitment of top researchers and the march to excellence can continue. In its relatively short history, UPCI has achieved recognition as a leading contributor to basic, translational, and clinical cancer research. As the institute’s funding and prestige in national rankings have grown over the years, it has, likewise, become more closely associated with the nation’s older, more established cancer centers. In addition, UPCI and the UPMC Cancer Centers now constitute one of the largest clinical cancer operations in the country and provide cancer care to

■ DNA-alkylating agents play a central role in many

human tumor therapies, yet resistance to these agents limits their effectiveness. Robert W. Sobol Jr., Ph.D., has shown that induction of two factors, O6-methylguanineDNA methyltransferase (MGMT) and base excision repair (BER) protein, is involved in such resistance. Modulating these factors may, therefore, provide a novel approach for increasing the effectiveness of alkylating drugs.

nearly half of the regional market, including more than 25,000 new patients per year. The influence extends far beyond the region, however; among UPMC’s most recent ventures are two new cancer centers in Ireland. As UPCI’s stature has grown, so has Herberman’s. Among his honors in recent years are the Governor of Pennsylvania’s Award for Excellence in Science and Medicine, a Lifetime Science Award from the Institute for Advanced Studies in Immunology and Aging, and the Solomon A. Berson Medical Alumni Achievement Award in Clinical Science from his alma mater, New York University. Herberman is himself a cancer survivor who has permanent loss of peripheral vision as the result of surgery to remove a tumor on his pituitary gland. A reserved, intensely personal man not given to idle rhetoric, he prefers to focus on making a difference in the lives of cancer patients rather than talk about himself. It appears that focus is paying off. For instance, Kirkwood’s pioneering research at UPCI has significantly advanced the treatment of melanoma, the deadliest form of skin cancer. Using a naturally occurring immune-stimulating protein, or cytokine, called interferon, Kirkwood’s group has demonstrated the regression of disease in some patients along with dramatic improvements in long-term survival. “Using interferon, we’ve seen a 25 to 35 percent reduction in relapse rates for patients with advanced melanoma, which is astounding considering this is a disease that has confounded medical science for more than 50 years,” says Kirkwood, director of the UPCI Melanoma Program. Based on a study he led, the Food and Drug Administration approved interferon as the first-ever adjuvant treatment for high-risk melanoma. Kirkwood is now studying whether interferon can improve melanoma survival rates by giving it to patients in earlier stages of the disease. He’s also working on a number of candidate melanoma vaccines that could give people at high risk for skin cancer a natural immunity against the disease. UPCI is making significant advances in the diagnosis, prevention, and treatment of many other cancers, including breast cancer, head and neck cancers, lung cancer,

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and cancers of the blood and lymphatic systems. For example, the Immunologic Monitoring and Cellular Products Laboratory, where Whiteside is the scientific director, assesses patients’ immune response to therapy; it can measure multiple parameters, including immune cell types and function as well as the cells’ ability to manufacture cytokines. “We now can detect cancer and cancer progression much earlier because we can look for 10 to 15 markers rather than the one or two we were able to study 20 years ago,” says Whiteside. “Using advanced technologies, we also can look for the presence of 30 different cytokines, which give us a good indication of how well a particular cancer is responding to therapy as well as which cancers are likely to respond to a particular therapy.” Whiteside also oversees a facility for generating cells and cellular products for cancer therapies like vaccines. The facility can genetically modify immune cells so they are better equipped to attack cancers. “At the moment, we’re developing

RON HERBERMAN HAS MY UNQUESTIONED RESPECT FOR HIS KNOWLEDGE OF AND COMMITMENT TO CANCER AND FOR WHAT HE HAS BROUGHT TO THE SCIENTIFIC COMMUNITY AND TO PITTSBURGH. EVEN WITH ALL HE HAS DONE, HE’S VERY HUMBLE AND UNASSUMING.

products for as many as nine clinical trials, not only for cancer but also for other conditions such as HIV and diabetes,” Whiteside says. Her laboratory has a number of ongoing collaborations with industry, performing immunological studies on samples from patients involved in company-sponsored clinical trials. In addition, her lab is developing assays for companies that want to be able to measure a particular immunologic or molecular function resulting from a therapy, and it increasingly serves as a consultant to companies interested in developing immune cells for therapy. Herberman sees collaborations with industry as a significant and growing part of UPCI’s future. “To truly make an impact on cancer, we need to get these better diagnostic approaches and treatment strategies to the patients as quickly as possible. To do that, it will take intensive collaborations with industry,” he says. “Our job is to do the early research, and their job is to take the research to the bedside. However, the more we do this collaboratively, the faster that will happen.” Such developments make Herberman particularly optimistic about UPCI’s future. Perhaps most encouraging to him is the fact that he now has little trouble attracting people to join UPCI. “Recruiting is much easier these days. We’re now very widely known, and it’s much easier to get people to come and take a look and to take the job,” says Herberman. Indeed, what began with one or two employees in 1985 is now an institute of approximately 500 people, many of them highly respected scientists and physicians in more than 30 disciplines who have come from some of the world’s leading academic research centers. And why not? “We have great facilities, great people, a great environment, and people interact extremely well with one another,” Herberman says. “It’s a very nice place to work and be successful.” And as for Detre, “embarrassing” is no longer a word he uses to describe the availability of high quality cancer care in Pittsburgh. Now, when someone asks, he advises them to stay right here.

— ELSIE HILLMAN, PITTSBURGH PHILANTHROPIST

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Treating patients with care and compassion

CLINICAL CARE AND COMMUNITY

104 Pitt and UPMC 110 Student Volunteers 118 Concussion Program 122 Biopreparedness 124 Technology Development

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PITT AND UPMC

The paradigm for success that the School of Medicine and the University of Pittsburgh Medical Center have steadfastly followed in their symbiotic ascent to research and clinical excellence in recent years is rooted in a fundamental principle:

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UPMC

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THE FOUNDATION FOR EXCELLENCE

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he paradigm for success that the School of Medicine and the University of Pittsburgh Medical Center (UPMC) have steadfastly followed in their symbiotic ascent to research and clinical excellence in recent years is rooted in a fundamental principle: What’s good for one is good for both. However, the interplay between them is far more complex than the clasp of hands in partnership or

the mutual litany of praise about the benefits that each party brings to the table. This collaborative venture is characterized, first and foremost, by UPMC’s longstanding and robust financial support of the School of Medicine, which, in turn, has made investment in its research enterprise an institutional priority and has leveraged this local capital to garner increasingly favorable levels of external support, most notably from the National Institutes of Health. (See page 3.)

What’s good for one is good for both. However, the interplay between them is far more complex than the clasp of hands in partnership or the mutual litany of praise about the benefits that each party brings to the table.

The payoff from this dynamic has resulted not only in an ever-growing portfolio of tangible research results but also in a range of collateral benefits, including the spin-off of new and marketable technologies, improved visibility and stature for UPMC and the School of Medicine (as well as for the University as a whole), and the overall success of the clinical enterprise as evidenced by increases in patient referrals and the quality of clinical services. A diagram of this interplay would show one step leading to another, and another, and another in a continuous cycle but with an ever-widening sphere of influence, initially emanating from Pittsburgh throughout much of southwestern Pennsylvania and now, more recently, to far-off places, including Italy, Ireland, and Qatar. “Our mutually beneficial, decades-long relationship with the University of Pittsburgh in the health sciences is viewed as a model for other academic medical centers across the country,” says Jeffrey A. Romoff, UPMC’s president and chief executive officer.

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Arthur S. Levine, M.D., senior vice chancellor for the health sciences and dean of the School of Medicine, agrees. Catalyzing the translation of research into groundbreaking clinical models and, thereby, advancing the missions of both the medical school and the health system regionally and internationally has produced “a novel, if not unique, relationship,” he says. In blunt, no-nonsense language, what that actually means is that “we’re joined at the hip: UPMC can’t function without us, and we can’t function without UPMC,” Levine says. “The success of one is the success of the other.”

--The School of Medicine is one of six health sciences schools at the University of

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Pittsburgh, which today stands among the nation’s leading academic centers for biomedical research. Pitt is home to a growing number of world-class scientists engaged

artificial organ and medical device development, cancer diagnostics and therapy, cardiology, gene therapy, bioinformatics and computational biology, psychiatry, neuroscience, structural biology, developmental biology, and vaccine development.

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in a wide range of studies on topics as diverse as drug discovery and design, organ transplantation and immunology, tissue engineering and regenerative medicine,

INVESTMENT OF CLINICAL PRACTICE AND HEALTH SYSTEM INCOME IN Increased ACADEMIC ENTERPRISE Research Productivity,

One of the few objective benchmarks by which an academic medical center can evaluate its success is NIH support for research. Unlike reputational rankings, the

Increased patient referrals, Technology Transfer,

NIH process is the only nationally competitive, peer-reviewed metric available. By this criterion, Pitt has thrived, breaking into the top 10 list of funded institutions in

clinical faculty quality, Leverage to

1997—a shift in rank that occurs only rarely—and subsequently maintaining that enviable position. Since 1998, the University as a whole and the School of Medicine UPMC, one of the nation’s largest and most financially successful academic

clinical enterprise

health care systems, provides world-class medical services through its vast network of hospitals, cancer centers, specialized outpatient facilities, rehabilitation centers, University share formal contractual bonds that define their relationship. More importantly, both sides would say, is an appreciation for the mutual interdependence that enables Pitt to provide opportunities for clinical training, educational experiences, and research in virtually any medical specialty and that, likewise, enables the medical center to stand at the forefront of translating new scientific findings into innovative clinical care and to support the development of new medical technology. Together, Pitt and UPMC have raised the standard of medical excellence in southwestern Pennsylvania and positioned health care as a driving force behind the region’s economy.

--The School of Medicine’s success in sustaining research productivity stems from its adoption of a growth paradigm centered on this fundamental idea: In an academic medical center, research and clinical success are synergistic and interdependent; therefore, a strategic collaboration between the clinical and the academic enterprises will enhance the success of both beyond that which would occur with an investment in either one alone. The starting point for actuating this philosophy was to invest clinical income in research infrastructure, including facilities, equipment, and investigator start-up packages.

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and other programs. Although legally separate and distinct entities, UPMC and the

Improved Stature and Visibility for Clinical and Research Enterprises and the University as a Whole

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have both more than doubled their level of NIH support.

and overall success for the External Support

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Clinical growth at Pitt was led by organ transplantation, but this growth began

What began as a regional, middle-of-the-pack medical school and a voluntary

with a substantial investment in research. The University recruited Thomas E. Starzl,

consortium of six independent hospitals with which it was affiliated for teaching

M.D., Ph.D., in 1981, when liver transplantation was still a controversial concept.

purposes have evolved over the past 25 years into a vast health care system and one

Starzl assembled an interdisciplinary team of surgeons, immunologists, pharmacolo-

of the nation’s leading biomedical education and research institutions. The success

gists, and others and expanded his previous clinical and laboratory research. The

shared by the School of Medicine and UPMC has been notable and, in recent years,

Food and Drug Administration’s approval of the immunosuppressant cyclosporin in

more far-reaching than ever. Perhaps the most pronounced example of their growing

1983, based largely on Starzl’s clinical experience with the experimental drug, greatly

international influence is the Pittsburgh-Palermo connection.

improved graft survival and long-term outcome. In 1986, UPMC invested $230 million

In 1996, UPMC partnered with the Region of Sicily and two hospitals there to

to expand the transplantation program as well as to provide space for the health

establish the Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione

system’s fledgling cancer institute and other research initiatives. By 1988, more than

(ISMETT—the Mediterranean Institute for Transplantation and Advanced Specialized

half the world’s liver transplants were performed in Pittsburgh, generating excep-

Therapies) in Palermo, Italy. ISMETT opened a new, state-of-the-art, 70-bed specialty

tional clinical revenue.

hospital, managed and operated by UPMC, in 2004 with a clinical focus on trans-

To maximize UPMC’s investment of clinical revenue, the School of Medicine

plantation and other therapies for patients with life-threatening organ failure.

created mechanisms to impel new research initiatives, including technologically rich

UPMC physicians practicing at ISMETT hold faculty appointments in the School of

core facilities in genomics, proteomics, bioinformatics, clinical research computing,

Medicine, and the Palermo facility is linked via a telecommunications system to its

imaging, and others for use by multiple investigators. Other research-support

affiliated network of UPMC hospitals in Pittsburgh.

resources for faculty included technical assistance in grant preparation and active

As an outgrowth of this venture, planning is now under way for a $398 million

guidance in technology commercialization. The ensuing faculty success in reporting

Biomedical Research and Biotechnology Center to be built near Palermo. The facility,

their research findings, especially those related to significant clinical advances,

which would be funded by the Italian government, is to be managed by UPMC.

promoted the visibility and prestige of the two partner institutions in the world of

Research, to be directed by the School of Medicine, would focus on such areas as

academic medicine and biomedical research, leading to the increased clinical

drug discovery, vaccine development, tissue engineering and regenerative medicine,

volume and robust financial performance that is the cycle’s entry point.

molecular imaging, and computational and structural biology—all of which are the

This increasingly dynamic research climate also led to more faculty entrepre-

medical school’s current and developing areas of research strength.

neurship—along with subsequent benefits. For example, Stentor, a start-up company

Other recent international ventures have seen the Whitfield Cancer Centre in

based on medical imaging technology, was formed in 1998 as a result of collaborative

Waterford, Ireland, and Beacon Hospital Cancer Centre in Dublin added to the growing

development efforts by University and UPMC researchers. When Philips Medical

network of UPMC Cancer Centers. UPMC also recently entered into an agreement to

Systems, a division of Royal Philips Electronics, acquired Stentor in 2005 for approx-

help improve the emergency medical care system in Qatar by providing training for

imately $280 million, UPMC realized a $36 million gain from its research investment

physicians and other first responders.

and the medical school received nearly $11 million as a result of the transaction.

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UPMC’s Strategic Business Initiatives division was subsequently launched, in part, with the profit from this deal to create and manage small companies, many based on faculty-developed technologies. Meanwhile, the School of Medicine adopted a variety of strategies to sustain this model of success. Interdisciplinary doctorates in fields like integrative molecular biology and molecular biophysics and structural biology were developed, as were research requirements for medical students. In addition, preference was given to hiring basic scientists whose research themes foster translational research and to focusing on platform disciplines like structural and computational biology, pharmacology, developmental biology, and biomedical informatics. Interdisciplinary research and “team science” were not just encouraged but made the cultural norm, with the development of multiple centers and institutes providing a physical or “virtual” environment for topic-specific intellectual interchange that has helped nurture the recruitment and sustain the retention of faculty.

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For Pitt and UPMC, success has been an outcome with many contributing factors: institutional commitment to excellence in their entire enterprise—research and clinical—backed by strategic investments and initiatives, strong and progressive leadership, strategic facility expansion, and recruitment and retention of personnel with the expertise to ensure sustained results. The most critical factor, however, has been UPMC’s financial and philosophical support, which sparked the School of Medicine’s ascendancy to research prominence. The health system’s widening sphere of influence, both at home and abroad, will enable it to continue to invest in the medical school—the starting point of their mutual paradigm for success.

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ince 1997, the Pittsburgh Schweitzer Fellows Program, part of the U.S. Schweitzer Fellows Program, has been involving students from various local schools in serving needy individuals and communities and developing

in them leadership skills and a commitment to community service. Over the course of one year, Schweitzer fellows receive a $2,000 stipend to create and implement their own program to benefit underserved populations in the Pittsburgh area. Currently, the School of Medicine has several students with Schweitzer Fellowships, and many of them have a long record of volunteering in their communities. Glaivy Batsuli started volunteering at an early age with her mom, and, as her family tells it, she’s been talking about being a doctor since she was 6 years old. Her parents are immigrants, and witnessing their experiences with health care in the United States further inspired her to spend her free time working in the community while growing up. Medical school keeps her busy, but “it’s good to be around ‘normal’ people—you know, people who don’t study all the time,” Glaivy says with a laugh. She heard about the Schweitzer Program in her first year when she was looking for community involvement activities and became interested in it because,

TAKING IT TO THE

STREETS STUDYING, WORKING ON NO SLEEP AND CAFFEINE, AND MORE STUDYING — THIS IS THE IMAGE PEOPLE OFTEN HAVE OF A MEDICAL STUDENT’S LIFE. WHILE THIS IS GENERALLY TRUE, MANY PITT MEDICAL STUDENTS FIND THE TIME AND ENERGY TO VOLUNTEER EXTENSIVELY IN THE PITTSBURGH COMMUNITY— IN ADDITION TO MANAGING THE BUSYNESS OF THEIR FOUR YEARS OF LEARNING. HERE ARE SOME OF THE WAYS IN WHICH THEY USE THEIR MEDICAL EDUCATION TO SERVE OTHERS.

as she puts it, “it allowed me to develop my passion.” For her fellowship, Glaivy and another Schweitzer fellow, Jean Lin, created a program for adolescents at the Sarah Heinz House, a local facility of the Boys & Girls Clubs of America, to promote participation in and better attitudes toward exercise. Glaivy and Jean knew that physical activity decreases in children as they grow older and that some of them dislike sports by the time they enter middle school because of the increasing focus on competition. Both students hope that their program, which begins each session with a short educational component, will inspire a lifelong interest in physical activity. “As a second-year medical student, I don’t often get to directly affect people’s health,” says Jean, “but with this program, I’ll definitely see results.”

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The best part of medicine, Schweitzer Fellow Narges Farahi says, is the direct contact with people and the possibility of affecting their lives by bettering their health. Narges says she was raised in a socially conscious family and was taught to use her education and skills to give back to the community. Her interest in health care was sparked by working with an immunization program in Paraguay; her subsequent participation in Teach For America, an education program serving some of the nation’s lowest-income communities, made her realize that medicine was the way that she could most influence people’s lives for the better. Both experiences led her to apply to medical school. For her Schweitzer project, Narges pulled from her experiences after college of working in children’s health care in Tanzania, where she first heard about rapid HIV

GLAIVY BATSULI

testing (the results are preliminary and known in 20 to 90 minutes). She was shocked to realize, while conducting a local workshop on hepatitis C and HIV, that most of the patients there didn’t know their HIV status and were at high risk for contracting AIDS. Many of them had been tested at some point in the past but, for various reasons, had never received their results. She subsequently started a project to use rapid HIV testing for dual-diagnosis patients (those with substance issues and psychiatric conditions) and said she hoped to initiate rapid HIV testing and HIV counseling at other community programs throughout Pittsburgh. “My first year in medical school was really hard because it was all basic science, with few opportunities to have contact with patients,” Narges says. “Working in the community has helped me remember why I wanted to get into medicine in the first place.”

--Erin Imler not only knew she wanted to study medicine, but she also earned guaranteed admission to the School of Medicine while still in high school (provided, of course, that she fulfilled certain requirements as an undergrad). Like Glaivy, Jean, and Narges, Erin has volunteered extensively throughout her life and plans to continue

“AS A SECOND-YEAR MEDICAL STUDENT, I DON’T OFTEN GET TO DIRECTLY AFFECT PEOPLE’S HEALTH, BUT WITH THIS PROGRAM, I’LL DEFINITELY SEE RESULTS.”

doing so when she finally becomes a doctor. At Pitt, she has volunteered at places like the Birmingham Free Clinic (a walk-in center for people without insurance or little access to health care) and the Women’s Center & Shelter of Greater Pittsburgh; her clinical rotation with the Indian Health Service in Arizona helped solidify her interest in working with underserved populations. Erin set up her Schweitzer project at the Matilda Theiss Health Center as a diabetes self-management group where people can share frustrations, ideas, and information about nutrition and physical activity. She has also arranged for eye exams and glaucoma screenings for people in the group through the School of Medicine’s Ophthalmology Interest Group and hopes to set up similar opportunities for dental and podiatry care. Erin says, “This experience has been really exciting.I hope to continue working with underserved populations, especially in a rural setting.”

JEAN LIN

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ESL HEALTH LITERACY PROGRAM

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some of the communities in which SNMA members regularly work. Westinghouse

relate to how difficult it can be to assimilate to life in the United States. He knows

High School is one of the places he volunteers with SNMA to tutor and mentor

what it’s like to negotiate new situations in an unfamiliar culture and to hide that

students and—most importantly, he believes—to show them that studying and

he feels wildly out of place. His experiences in moving to the U.S. from Nigeria are

doing well in school will serve them well in the future. “They can see me and where

part of his drive to help Somali Bantu refugees who have been relocated to

I am and know that school isn’t a waste of time,” Barrett says. When he first began

Pittsburgh. Reggie co-coordinates the English as a Second Language (ESL) Health

mentoring a group of Westinghouse students, they were failing their courses; but

Literacy Program initiated by Pitt medical student Susan Wong and funded by the

with his consistent presence and the introduction of a little healthy competition

Caring for Community Grant Program through the Association of American

among the students, their grades improved. “It was rewarding to see their spark,”

Medical Colleges and the Pfizer Medical Humanities Initiative. Somali Bantus, a

Barrett says. “It’s important for them to see that being successful in school is accom-

persecuted minority in Somalia, have not been permitted to attend school in their

plishable and that they’re not any less gifted than students in other schools.”

homeland and, therefore, are mostly unable to read or write. After walking for miles

ommunity service is at the heart of Pitt’s chapter of the Student National Medical Association (SNMA), as it is for member Barrett Woods and his medical school experience. He grew up in Pittsburgh and is familiar with

Barrett has benefited from mentoring himself. He cites Robert D. Bennett, M.D., clinical assistant professor of surgery, and former faculty member Henri R. Ford,

edical student Reggie Anunobi may not know what it’s like to flee on foot to another country to survive a civil war or live a tenuous existence in a refugee camp for years, but, like many of the people he helps, he can

out of Somalia and living in refugee camps in Kenya for a number of years, some of them began arriving in Pittsburgh in 2004.

M.D., as mentors who supported his decision to go into medicine. Likewise, he credits

Four times a month, Reggie and other volunteers teach the refugees about

other medical students, including Nicole Christian and Bradley Stephens, as being

hygiene and personal health care-related issues. Many American behaviors are new to

instrumental in the progress made by SNMA. One of Barrett’s biggest goals is to

them, and the volunteers help the refugees adapt and learn things like the difference

secure funding to establish a mentoring program for young adults in the city. Mean-

between dish soap and detergent, and that all foods available in the store aren’t

while, he is also active in some of SNMA’s other programs, including HIV awareness

necessarily nutritious. (Children of the refugees encounter junk food for the first

sessions at the Shuman Juvenile Detention Center and health screenings and meal

time here, and they must learn that candy bars aren’t meant to be eaten as meals.)

preparations at the East End Cooperative Ministry’s men’s shelter and soup kitchen.

“The concept of preventive medicine is very new to them,” says Reggie. “Why would

Barrett intends to be involved in any community where he lives, be it Pittsburgh

they go to the dentist twice a year if nothing is wrong? Flossing their teeth means

or elsewhere. He says, “I feel blessed in my life, and I have a responsibility to reach

very little to them, but we explain how important it is in the long run to maintain

back into the community.”

healthy teeth and gums.” The Somali Bantu families in Pittsburgh speak a dialect called Maay Maay, which almost no one in the region speaks, so volunteers often

A $90,000 LEGACY Members of the Class of 2009 aim to do more than leave the University of Pittsburgh with a medical degree. With the “90K from 2009” project, they have pledged to raise at least $90,000 before their graduation to benefit Pitt’s Program for Health Care to Underserved Populations (PHCUP). Leading the campaign are Class of 2009 students Brett Michelotti and Lauren Toney, who see this initiative as part of the ongoing legacy of community service by Pitt medical students. Brett calls it “a testament to the calling of our future profession and a model of our commitment to society.” PHCUP, which operates through the Department of Medicine’s Division of General Internal Medicine, serves the region’s uninsured population through four free health care clinics and operates

with only a volunteer staff of clinicians. Many medical students begin working with the Pittsburgh community by volunteering their time and expertise to the Birmingham Free Clinic, one of the four PHCUP facilities. Brett and Lauren have plans for various fundraisers, including a wine-tasting /silent auction event. The Class of 2009 hopes to end its time in Pittsburgh by strengthening PCHUP and its ability to improve health care throughout the greater Pittsburgh area. “This ambitious endeavor reflects the generous and altruistic spirit that exemplifies the best of our medical school community,” says Arthur S. Levine, M.D., senior vice chancellor for the health sciences and dean of the School of Medicine.

use PowerPoint presentations with pictures to help illustrate their lessons. Reggie is responsible for encouraging other students to participate in the program, writing the curriculum, and getting supplies for teaching sessions. Like other Pitt medical students who volunteer in the community and still manage to keep up with their studies, Reggie says that maintaining the balance is simple; he just makes time to help others. The reason he’s studying medicine is because of its inherent intellectual and human components; medicine is a field that satisfies his interests and allows him to make a difference in other people’s lives. He hopes to do his residency in Nigeria, which is where he worked one recent summer with a doctor from Vanderbilt University to teach physicians how to do procedures with whatever resources were available—like how to diagnose an injury without an X-ray machine. Wherever Reggie ends up, he hopes he can return to Nigeria to work in hospitals for one or two months a year. “I can’t just come to the U.S. and make money,” he says. “That’s too selfish. I have to go back and help with my expertise.”

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HE LPIN G WI TH HE ALI NG I N HOND UR AS When the opportunity arose to spend two weeks of her family medicine rotation in a remote village in the mountains of Honduras, Cecily Agcaoili was excited and unfazed by tales of omnipresent mud, no electricity, frigid showers, and people with illnesses of which she had never heard. Instead, she wondered whether, as a third-year medical student, she had enough skills to help people who stood in line for hours at the clinic for a chance to be seen by a student like her. Fellow medical student Benjamin Tu also jumped at the chance to spend his rotation in San José del Negrito. He wondered how he’d be able to work around the language barrier and whether his medical knowledge so far was adequate. Both students were in Honduras with the Pittsburgh chapter of the nonprofit health care partnership Shoulder to Shoulder. A member of the Global Health Medical Education Consortium, William Markle, M.D., clinical associate professor of family medicine and director of the UPMC McKeesport Family Medicine Residency Program, chose San José del Negrito as a place with which he could form a collaboration with Shoulder to Shoulder to provide health care. The village had established a health

committee and had the infrastructure needed to work with a Shoulder to Shoulder team. (All health care in the village is provided in Spanish, Markle says, and caregivers not only become adept at working with interpreters but also find that their own fluency, if limited, improves quite a bit.) With Markle, Randall Kolb, M.D., director of the UPMC Shadyside Family Medicine Residency Program, and Mark Meyer, M.D., a family physician practicing in East Liberty and president of the local Shoulder to Shoulder chapter, have recruited health care professionals and medical students to volunteer in San José for two-week brigades twice a year since 2000. Cecily was in the cohort in spring 2006 and Ben in fall 2005. Once they arrived, they had no time to worry about their qualifications. Each day after breakfast, group rotations began with either seeing patients at the clinic, running the pharmacy, or working on community projects that students designed themselves, such as monitoring local children’s nutrition and villagers’ compliance in taking medications. Their days ended with a senior physician’s special presentation or talk about cases they encountered that day. Then they’d get to strap on headlamps, play some cards, and maybe play with the local children.

Sometimes they were exhausted from hiking hours a day to set up a temporary clinic for people who lived too far away from the village to travel there easily. Other times, they worked on a way for people who couldn’t read their prescriptions to know when to take their medication. (One way was to attach preprinted stickers with the symbol of a rooster for morning, a sun for midday, and a moon for evening to the plastic bags or bottles containing villagers’ medicines.) In all cases, they had to think quickly and trust what they had learned about medicine so far, even if senior physicians and residents were nearby for a quick consult or question. Often, Cecily and Benjamin had to acknowledge that some ailments required treatments and supplies they didn’t have there. Benjamin remembers meeting an older man who had been relieving a toothache by dabbing it with battery acid. “It was tough,” he says. “I’m not a dentist, but I was able to tell him to stop using the battery acid, dispense some Tylenol for relief, and give him a toothbrush and toothpaste so he’d have a chance for better oral hygiene.” Both students liked the community atmosphere where they saw patients a couple of times and were able to check on their progress. Cecily enjoyed the

continuity of care so much that she changed her focus from pediatrics to family medicine; and the experience confirmed Benjamin’s decision to work with underserved populations. “I became really interested in people’s perception of health care when they don’t have it regularly; and to see people become more empowered to care for their own health rejuvenated my feeling of why I went into medicine in the first place,” he says. Cecily agrees that her experience in Honduras affirmed her choice of medicine as a career and “made me totally fall in love with medicine again.” Both students returned to Pittsburgh with a renewed sense of confidence in their skills, especially when faced with less-than-ideal circumstances. “It was great to see all that I’ve studied, even the small things everyone said you’d never need to know, come to life,” says Benjamin. Cecily was left with an enthusiasm for the rest of her studies. “I feel very prepared for anything,” she says. “It was definitely the best experience I’ve had in medical school.”

Vincent Lee, a Pitt medical student who also completed a clinical rotation in Honduras, provided these photos of some of the sites from his experience.

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octors at the UPMC Sports Medicine Concussion Program sometimes see famous athletes in their waiting room, but not for the best of reasons. After suffering serious head trauma in a highly publicized, off-season motorcycle accident, followed by a concussion in a game midway through the 2006 season,

Pittsburgh Steelers quarterback Ben Roethlisberger came in

for evaluation. He had to pass several tests to assess his cognitive

abilities and whether or not his symptoms had subsided before being cleared to resume playing football. Other athletes aren’t so fortunate. In early 2007, San Francisco Giants catcher Mike Matheny announced his retirement from baseball after doctors in the program tested him and found that, almost a year after a concussion caused by a series of foul tips to the face mask, he was still experiencing symptoms of head trauma. The Sports Medicine Concussion Program has established an international reputation in the diagnosis, evaluation, and management of sports-related concussions in athletes at all levels, from professional to college and even high school. Established in 2000, the program’s patient base has grown every year to nearly 2,400 patients in 2006. The program’s founding director, Mark R. Lovell, Ph.D., associate professor of orthopaedic surgery and director of neuropsychological testing programs for the National Football League and the National Hockey League, can relate to what the athletes experience postconcussion. When he was 18, he was in a car accident and sustained a concussion. “I still can’t remember a lot of what happened in my senior year of high school,” Lovell says. What primarily draws athletes to the program is a test called imPACT™ (Immediate Postconcussion Assessment and Cognitive Testing) developed by Lovell along with Joseph Maroon, M.D., who is currently a clinical professor of neurological surgery. The computerized test, which is designed to objectively evaluate the severity of concussions and more accurately determine if and when an athlete can return to play, is composed of six sections and evaluates visual processing speed, memory,

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attention, and other elements of cognition. Lovell came up with the idea for imPACT when he started working with the Steelers more than a decade ago. He and other doctors were testing each player’s cognitive skills preseason and using stopwatches

10

Concussions cause changes in brain function that can last from 24 hours to 10 days or longer.

to time their responses to different tests. “I wanted to do the same tests but more accurately and with fewer personnel, and computers were really starting to get big, so it seemed perfect to create a computerized test,” says Lovell. Now, imPACT is being used worldwide by many high school, collegiate, and professional sports teams. A recent study by Lovell and colleagues confirmed the value of such neuropsychological testing through the use of functional magnetic resonance imaging (fMRI), one of the few scanning tools that can show brain activity, not just anatomy. Even the Centers for Disease Control and Prevention (CDC) has tapped the Sports Medicine Concussion Program’s expertise. Michael W. Collins, Ph.D., assistant director of the program and assistant professor of orthopaedic surgery, was a key

3.8

Up to 3.8 million sports-related concussions are thought to occur each year in the U.S.

contributor to the CDC’s recently revised multimedia information kit designed to educate physicians about earlier diagnosis, management, and appropriate referral for concussion patients. “No two concussions are alike, and the injury’s effects and recovery period are different in each individual,” Collins says. “That’s why education for both patients and doctors about proper management is essential.” In addition to clinical care, the Concussion Program is engaged in pertinent research like that of Collins, who conducted a study that supported the commonly held notion that, after one concussion, high school athletes will experience more and increasingly severe symptoms with subsequent concussions. Lovell’s research has shown that NFL athletes recover from a concussion faster than high school athletes, which also underscores the careful handling and proper recovery time that younger people need postconcussion. The number of concussions

SPORTS HAVE CHANGED. KIDS ARE STRONGER, BIGGER, FASTER, AND HIT HARDER. WOMEN’S SPORTS HAVE DEFINITELY GOTTEN MORE AGGRESSIVE, AND WE’RE NOW STUDYING CONCUSSIONS IN FEMALES SPECIFICALLY.

in younger players is increasing because “there’s increased recognition and we’re better at diagnosing the injury,” says Lovell. “Plus, sports have changed. Kids are stronger, bigger, faster, and hit harder. Women’s sports have definitely gotten more aggressive, and we’re now studying concussions in females specifically,” he adds. The clinical approach followed by the program is to effectively manage a concussion. “There are two essentials in dealing with concussions. One is properly identifying the injury and getting the player off the field immediately, and the second is giving the player enough time to rest. Too much mental or physical activity can delay the

10%

Approximately 10% of all athletes involved in contact sports have a concussion each season.

63%

Of the concussions that occur each year in high school athletics, 63% happen in football.

recovery process,” says Lovell. Experiencing a second concussive injury while recuperating from an initial one is especially dangerous in that it can cause even greater brain trauma. Lovell says athletes are not cleared to play again until they undergo a magnetic resonance imaging exam and an imPACT evaluation, do cardiovascular exercise, display no symptoms, and successfully complete this sequence several times. To more accurately judge the normal cognitive condition of each player, “Big Ben” Roethlisberger and his teammates are tested with imPACT at the outset of their careers with the Steelers. If they do sustain a concussion, then baseline data exist so doctors can assess the extent of their damage in a more individualized manner. “All of this keeps me busy, but I enjoy the work,” says Lovell. “I get to work with athletes and travel the world, bringing imPACT and concussion education to people. I feel like it’s making a difference.”

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UPMC echoes this emphasis on all-hazards disaster planning. “UPMC’s innovative approach to preparedness must extend beyond expected types of emergencies. It must address potential threats about which there are limited scientific facts and multiple variables,” says Loren H. Roth, M.D., M.P.H., the health system’s chief medical officer. At the School of Medicine, various aspects of preparedness are woven throughout the curriculum rather than addressed in a single course. Topics like bioterrorism agents and pandemic influenza, for instance, are covered in the first-year medical microbiology course, while pharmacologic aspects of chemical weapons agents are integrated into second- and fourth-year pharmacology courses. Every eight weeks during the third-year medicine clerkship, a lecture on emerging infectious diseases is presented. Such initiatives are ongoing and subject to constant review to keep them current. Likewise, specific, hands-on training is being developed and implemented. All students are taught how to select and fit-test an appropriate breathing apparatus; still to come are lessons on personal protective equipment and decontamination. An annual exercise for third-year students simulates the drama of a PREPARING FOR MODERN THREATS

pandemic influenza outbreak that inundates a hospital with infected patients. This role-playing drill is designed to teach students not only how to care for patients in a crisis as supplies run short, hospital workers themselves fall ill, and the mortality

P

andemic influenza. Smallpox. Anthrax. Ebola. Radiation poisoning

rate climbs, but also the importance of leadership, cooperation, and teamwork.

from a “dirty bomb.” These and other 21st century threats to public

In the early planning stages is an initiative to prepare students to assist UPMC in

health and safety are potentially devastating and require inno-

the event of a major disaster, if needed, in providing patient care on a massive scale

vative and extensive preemptive planning to counter such risks.

to the extent that their level of training would allow. First-year medical students, for

Both the School of Medicine and the University of Pittsburgh

example, could take vital signs and help move patients, whereas third-year students

Medical Center (UPMC) are actively engaged in extensive and

could variously assist a patient care team. Students would be trained each year to

often collaborative efforts to anticipate and prepare for how they as institutions —

anticipate — regardless of what the crisis might be — what types of tasks they could

and how the people who comprise those institutions — would respond.

be expected to perform, whereas UPMC personnel would be briefed regularly to

Even more fundamentally, the approach adopted here to teaching medical students about the public health threats — whether from biological attacks, disease

know what each level of student is capable of doing and, therefore, what kind of help to expect from them.

epidemics, or natural disasters — that they might face someday as physicians is

The logistics of this initiative, which could encompass other health sciences

inclusive: “Almost anything is a potential threat, the thinking goes, so prepare for

students beyond the School of Medicine, are being developed in synchrony with

all possibilities,” says John F. Mahoney, M.D., associate dean for medical education

UPMC’s comprehensive planning efforts, which entail the anticipation of quaran-

and associate professor of emergency medicine.

tine, protection, and vaccination issues in the event of an outbreak of a contagious

While this approach might seem inordinate, the logic is clear. Modern threats

disease like smallpox or avian flu as well as the vast range of other considerations

to society are so pervasive that preparing intensively to deal with any single one of

in preparing for natural or man-made disasters or other emergencies. “UPMC makes

them is unlikely to pay off. “Twenty hours of anthrax training won’t counter an

emergency preparedness a top priority,” Roth says.

ebola outbreak,” Mahoney notes. “Instead, the all-hazards approach to preparedness

Underlying all of these efforts on the parts of both UPMC and the School of

provides a basic understanding and awareness of specific threats but emphasizes

Medicine is not only anticipation of the leadership that would be expected of them

fundamental principles that can be followed regardless of what the specific threat

in the event of a cataclysmic event but also the realization that the best time to

turns out to be.”

grapple with one is before it occurs.

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THE HAND OF A 9-YEAR-OLD ARTHRITIS PATIENT BEFORE (LEFT) AND FIVE DAYS AFTER TREATMENT. BOTH THE PATIENT’S SWELLING AND INFLAMMATION (SHOWN IN RED IN THE IMAGE) HAVE IMPROVED SIGNIFICANTLY WITH TREATMENT.

The University of Pittsburgh takes pride in contributing actively to regional economic development through commercialization of University-derived technologies, particularly in western Pennsylvania’s emerging biomedical and life sciences sector. However, a new start-up doesn’t just happen overnight. Rather, these efforts most often take many years of development within the University; many years of hard work by licensees, which are themselves often fledgling enterprises; and many business and financial partners before ideas become marketable products and start-up ventures become established companies. The following is a profile of one such work in progress.

localized warmth. And these two seem to be enough. “Combining that information, we can derive an index of what the disease is like in a given joint,” says Hirsch. The quantitative measures provided by the imaging technology offer a more consistent and reliable way to track disease over time. Because the process is fast (less than a minute) and noninvasive, patients can have images made while waiting to see the A TECHNOLOGY DEVELOPMENT SNAPSHOT

doctor. “Instead of spending half an hour trying to physically examine every joint,” says Hirsch, “you can focus on the joints of interest.” Hirsch and colleagues tried for two years to get research funding from the

olor, calor, rubor, and tumor —pain, heat, redness, and swelling.

National Institutes of Health to optimize their technology, but to no avail. They also

These are the four classic signs of the inflammatory response. For

submitted an invention disclosure to Pitt’s Office of Technology Management, and

D

years, Raphael Hirsch, M.D., chief of pediatric rheumatology at

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Children’s Hospital decided to file a provisional patent on the technology.

Children’s Hospital of Pittsburgh of UPMC, had been trying to

When he reviewed the invention disclosure, Marc Malandro, Ph.D., Pitt’s associate

figure out how to measure these signs in his young patients with

vice chancellor for technology management and commercialization, thought Hirsch

juvenile rheumatoid arthritis (RA) in a more quantifiable way than

and colleagues were onto something. However, he knew the group needed business

the routine physical exam of the joints. He knew from his own experience, as well as

expertise to move to the next levels in refining their technology, defining their target

from published research, that even experts will evaluate the severity of the same

market, and outlining their value proposition. He suggested that they get in touch

inflamed joint differently and that the same expert’s judgment may vary from exam

with two local economic development organizations with which Pitt collaborates

to exam. He also knew that available technologies, like X-ray, MRI, and ultrasound,

regularly. The Pittsburgh Life Sciences Greenhouse (PLSG) provided not only $150,000

were not effective in evaluating disease activity in RA and were not economically

of early-stage funding but also the expertise of Fred Marroni, a PLSG executive in

viable or user-friendly for routine office-based use. Hirsch was determined to find

residence with significant international experience in imaging-related industries. A

something better. However, it wasn’t logic but location that put him on the path

second regional commercialization enterprise, the Idea Foundry, came up with an

to success.

additional $175,000.

Hirsch’s next-door neighbor happens to be Richard D. McCullough, Ph.D., vice

With Marroni on board, the group decided to participate in the Pittsburgh

provost for research at Carnegie Mellon University. The two were talking about Hirsch’s

Technology Council’s business plan development contest, Enterprise 2006. The

challenge, and McCullough put him in touch with faculty at Carnegie Mellon’s

venture took top honors in phases one through three of its business development

famed Medical Robotics Technology Center. Then, with C. Kent Kwoh, M.D., a Pitt

process. “But it wouldn’t have worked without PLSG and Fred,” confides Hirsch.

rheumatologist who cares for adults with RA, the group came up with an off-the-shelf

In July 2006, the entrepreneurs took the plunge of forming a biotech start-up

combination of three-dimensional and thermal imaging and their own proprietary

among three partners—the University of Pittsburgh, Children’s Hospital, and Carnegie

rating algorithms to quantify two of the four signs of inflammation—swelling and

Mellon University. But they didn’t make a public announcement about the new

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company until January 2007, at which time the formation of Arthritis Imaging Inc. was formally announced by PLSG. However, Marroni, applying his business development savvy, could clearly forecast applications for the technology beyond arthritis to other diseases that manifest as surface inflammation like skin diseases and pressure ulcers. The corporation was renamed Cartesia Dx, while its initial product remained Arthritis Imager. And, true to the intent of the PLSG executive in residence program, Marroni thought Cartesia Dx was the next good fit for his own expertise, so he

Clyde B. Jones III

became the company’s founding president and CEO. Hirsch and Kwoh serve on the company’s scientific advisory board, along with Carnegie Mellon’s James Osborn. The product, which, in its ultimate form, will probably look something like a small desktop igloo, will be targeted initially to pharmaceutical and contract research organizations conducting arthritis-related clinical trials. Since the Arthritis Imager can provide objective measures and patient documentation taken at different time points (for example, before and after treatment), it promises to substantially reduce both the number of subjects required for a clinical trial and the time to market for the

INVESTING IN A WINNER

intervention being evaluated. Once the technology is optimized and priced competitively (ideally under $100,000), Hirsch hopes to see it in every rheumatologist’s office. At Pitt, which is intensifying its technology commercialization efforts and its outreach to faculty about the potential innovation opportunities waiting to be realized from their research, Malandro points to Cartesia Dx as a multidimensional successstory-in-process: “We have technology licensed from two universities, active partnership with UPMC, and both financial and business development support from two regional economic development organizations. This is exactly how we like to see the process work. It’s good for Pitt and it’s good for the region.”

E

veryone likes to invest in a winner. The University of Pittsburgh is indeed fortunate that as our reputation and national rankings have continued to rise in recent years, so has the number of individuals, corporations, and foundations that recognize us as a wise investment. Thanks to this generosity, the Schools of the Health Sciences, led by the School of Medicine, helped the University reach the

$1 billion goal of its capital campaign, begun in 1997, nearly a year ahead of schedule. Our success has given us the confidence to move forward, expanding the campaign goal to $2 billion, with the expectation that, when complete, the campaign will have raised at least $1 billion for our six health sciences schools, of which $600 million will have been earmarked specifically for the School of Medicine. Since the formation of the University of Pittsburgh and UPMC Medical and Health

INNOVATION BY THE NUMBERS

Sciences Foundation in 2003, we’ve started to think differently about the way we engage our supporters. We know that philanthropy creates a partnership, which

“Innovation commercialization takes considerable time, investment, finesse, and generous doses of University support and perseverance,” says Marc Malandro, Ph.D., Pitt’s associate vice chancellor for technology management and commercialization. The University’s Office of Technology Management evaluates its success by the number of faculty who submit invention disclosures, the number of those ideas that can be turned into products, and the number of those products around which new companies can be developed, among others. In 2006, the most recent year for which data are available, more than 350 faculty members participated in the innovation and commercialization process, many of them from the School of Medicine. This increasing faculty involvement highlights the school’s desire to make innovation a central component of its academic endeavors. These 2006 numbers characterize the growing role of the School of Medicine in the University’s technology commercialization efforts.

Invention disclosures:

112

means responsibility on both sides to keep the lines of communication open so that we understand the things that each of us can do to have a positive effect on the way medicine is taught, the way research is funded, and the way health care is provided.

U.S. patents issued:

13 Licenses / options executed:

18 Total revenue:

$10.1 million

THANKS TO THIS GENEROSITY, THE SCHOOLS OF THE HEALTH SCIENCES, LED BY THE SCHOOL OF MEDICINE, HELPED THE UNIVERSITY REACH THE $1 BILLION GOAL OF ITS CAPITAL CAMPAIGN, BEGUN IN 1997, NEARLY A YEAR AHEAD OF SCHEDULE.

127

DONORS

DEVELOPMENT

128

With grateful appreciation for their generosity, we acknowledge the following individual, corporate, and foundation donors whose contributions of $500 or more to the University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, and Western Psychiatric Institute and Clinic between July 2003 and December 2006 have supported us in our academic, research, and clinical missions.

INDIVIDUAL DONORS

Edson R. Arneault Kathy W. and Stuart A. Arnheim

Adnan Abla, M.D. Elinor M. Abplanalp Mr. and Mrs. Don E. Ackerman

The generosity of our alumni and friends is the key to our having the resources needed to remain an institution of choice for the best and brightest. For example, our School of Medicine is consistently ranked among the nation’s finest and

Dale K. Adair, M.D. Mr. and Mrs. Joel P. Adams Ronald L. Adams William J. Adams

competes directly with Harvard, Yale, and other leading institutions for prospective students, but we don’t have the multi-billion-dollar endowments that many of

Douha Safar and Mounzer E. Agha, M.D.

those schools have. What will make the difference in our ability to attract and keep

Electra and James R. Agras Mr. and Mrs. Carl T.J. Ahlers

ability to offer the same type of financial assistance and scholarships that those

Renee Adrianne and Curtis E. Aiken

schools are offering.

Cheryl Shutts Albert and J. David Albert II, M.D.

‡Estate of Alice E. Bartberger

Glenn W. Arthurs

‡John P. Bartel

Mr. and Mrs. Bill Asnip Sr.

Elaine and Peter J. Bartkus

Eric N. Assimakopoulos Dennis L. Astorino

Susan J. Bartlett and David L. Bartlett, M.D.

Louis D. Astorino

Edward James Barvick, M.D.

Mr. and Mrs. Peter M. Augustine

Monette Green Basson, M.D., and Geoffrey Hugh Basson, M.D. Dipak K. Basu

Amada Awan and Rashid A. Awan, M.D.

Martha S. and Anthony J. Alfano

that we have the most up-to-date facilities in which they can do their work. Because

Nicholas James Alfano

of the growing need for investment in research, the School of Medicine is committed

Judi Cannava-Allen and Thomas E. Allen, M.D.

to further expansion of facilities, and that expansion is possible only through partner-

Edwin H. Beachler III Alex Azar, M.D. George Clifford Baacke II, M.D.

Barbara A. Dappert, M.D., and Michael J. Becich, M.D. Ph.D.

Thelma Ilyas Badwey and Robert E. Badwey, M.D.

Isabel Lubousky Beck, Ph.D. Nancy U. Douglass Beck

Sanjeev Bahri Annette W. and Robert L. Becker Jr. ‡William R. Baierl Ann D. and William W. Bain Jr.

G. Nicholas Beckwith III, Trustee, and Dorothy B. Beckwith

Clara Baird and ‡William F. Baird, M.D.

Dennis J. Beer, M.D.

Patty and Jay Baker

Jane Pickering Beering and Steven C. Beering, M.D.

Jodi Bowen Baldridge and Paul Lincoln Baldridge, M.D.

Richard J. Behan Trust

Jane K. and Christian Allison

Institutes of Health continues to stagnate, institutions like ours are finding that the

Penny Foster Alpern and Charles Harvey Alpern

gap can be made up only through private giving.

Bruce A. Americus

It’s encouraging to see that more and more people are coming to understand

Joan Ehler Ammer, M.D., and John L. Ammer, M.D.

Elizabeth Bates and James S. Bates, M.D.

Michael J. Axe, M.D.

Vincent Charles Albo, M.D.

faculty members and to make the ongoing capital investments needed to ensure

ship with philanthropy. Likewise, as essential research funding from the National

Rosalie Barsotti

Nancy Levine Arnold and Robert M. Arnold, M.D.

James Andrew Austin, M.D.

top students — and to ensure that they graduate without crippling debt — is our

At the same time, we need to keep recruiting and retaining top researchers and

Kathleen Barrow-Flory and Robert Hewitt Flory Jr.

Elaine Bellin Bette N. Balk and Phillip Balk, M.D.

that if they care about changing the face of academic medicine, then the University

Frank Alfred Anania, M.D.

of Pittsburgh School of Medicine offers a wise investment. I can’t think of a better

Lee R. Anderson

way to back a winner.

Lawrence R. Andrews

Joyce S. and Alan R. Bender Kenneth Raymond Balkey Gerard Mark Benecki, M.D. Richard Neil Baney, M.D. Donald Benn Arthur W. Banwell

Anita Angle

Susan and Robert Bennardo Robert Baraff, M.D.

Clyde B. Jones III

Bonnie Bantley Anton and Richard Paul Anton, Esq.

President

Ellen B. Bennett Arlene Brown Baratz, M.D., and Mark Everett Baratz, M.D.

Renee and George G. Benson

Debbie and Michael Barbarita

Kim L. Bentz and Michael L. Bentz, M.D.

Meera Appaswamy, M.D.

University of Pittsburgh and UPMC Medical and Health Sciences Foundation

Billy N. Appel, D.D.S. Alfred R. Barbour John M. Armitage, M.D. Charles Jack Bark, M.D.

‡ before an individual’s name indicates the person is deceased

Jacqueline M. and A. David Berestecky

129

130

DONORS

DEVELOPMENT

George Berg, M.D.

Debby and Daniel Irvin Booker

Stephen C. Bruno, M.D.

William H. Chambers, Ph.D.

Patricia H. and Charles T. Collins

William E. Danko, M.D.

Mary Murtland Berger

Lisa B. Bootstaylor, M.D.

Tina Fiorini Bruns

Ravi Champrasekhara

Yolonda L. Colson, M.D.

Sandra N. Danoff

Shilpa Beriwal and Sushil Beriwal, M.D.

Mary D. Bordt

Emily Kleiman Bua

Ernest E. Charlesworth, M.D.

William George Combs, M.D.

Edward J. Borkowski

James I. Bucher, M.D.

Courtney B. and Carl W. Borntraeger

Theresa Anne Bucher

J.W. Connolly, Trustee, and Shirley Connolly

Frances C. Dauber and James H. Dauber, M.D.

Sondra R. Berk and Robert Norton Berk, M.D.

Rebecca Morris-Chatta, Esq., and Gurkamal S. Chatta, M.D.

George A. Davidson Jr., Trustee, and Ada Davidson

Rita Maganbhai Patel, M.D., and Kenneth W. Boscha, M.D.

Donna and Robert M. Connolly

Deborah Levy Berkman

Manisha Chaudhary and Prett M. Chaudhary, M.D., Ph.D.

William S. Conover II

Jamini Vincent Davies

Darin Conti

Judy Stoeven Davies and Richard Davies

Julie Guadagnino Conway and John Joseph Conway

Malindi Davies

Anne Rush Cook, M.D.

Ada and Stanford P. Davis

Jamie Cooperman and Arthur Cooperman, M.D.

Grover T. Davis, M.D.

Charles Edward Copeland, M.D. James J. Corrigan Jr., M.D.

Nancy Noel Davison and Thomas Michael Davison, M.D.

Edward J. Berman, M.D. Sanford S. Berman Albert Michael Bernath Jr., M.D. Marilyn U. and Guy P. Berner David M. Bernstein Howard R. Bernstein William Bevan III Rebecca Jones Beward ‡Minnette D. Bickel Ruth Raupp Bielo, M.D. Marjorie Romkes, Ph.D., and William Lyman Bigbee, Ph.D.

Sylvia and Gregory A. Bosner

Michele Buck Rudolph L. Buck, M.D.

Barry Maurice Chauser, M.D. Alan P. Burckin, M.D. Mary Knowles and Ken Burgess

Liu Lun-Li Chen, M.D., and Alex Chen, M.D.

Robert P. Bowser, Ph.D.

Tracy R. Seewald, M.D., and Steven A. Burton, M.D.

Shirley M. Chervenick and Paul A. Chervenick, M.D.

Arthur Dean Boyd, M.D.

Cynthia S. and Lawrence S. Busch

Dorothy L. Boyer

Sylvia Amdur Busis

Bette Brown Chidester, M.D., and Paul Donald Chidester, M.D.

Kerry S. and Paul Vincent Boulian James N. Bower, M.D.

Susan and Michael Boyle Stephanie and Michael Bozic

Sara Davis Buss and John W. Buss Jr.

Sally Hillman Childs and ‡ J. Mabon Childs

Karen Scurci Buterbaugh and Glenn A. Buterbaugh, M.D.

Marietta and Sam A. Cosentino

Ellis S. Day Jr.

Otis H. Childs

Kathleen M. and Jeffery E. Bradey

Charles Louis Cost

Susan Criep De Santa-Cruz

Edward G. Byrnes Jr.

Jean Hill Chisolm

Betty H. Bradley, M.D.

Frances Miale Cost

Bonnie Lyons Dean

Alan David Christianson, M.D.

Bruce Maclean Coull, M.D.

Catherine D. DeAngelis, M.D., M.P.H.

James Steven Brady, M.D.

‡Estate of Thomas E. Cadman, M.D. Michelle Simonet Caesar, M.D.

Neil Alexander Christie, M.D.

Robert Whipple Bragdon, M.D.

Frank V. Cahouet, Trustee, and Ann W. Cahouet

Yoon-Kyu Chung, M.D.

Christopher O. Branam, M.D.

Joseph E. Calderone Jr., M.D.

Gene P. Ciafre

Joan and Thomas G. Bigley Timothy R. Billiar, M.D.

Suzanne and Robert Chute

John P. Brandt, M.D. Renard L. Biltgen Virginia M. Brasuk, M.D. Marcel Binstock, M.D.

Joseph L. Calihan

Gregory Alfred Bisignani, M.D.

Frank Bittner Jr. Astrid Bitzer John Frederick Bitzer III Kathy and John N. Blackman Michael R. Blaha David A. Blandino, M.D. Estelle Edwards Blanton H. Vaughan Blaxter III Sherley T. Blaxter Patricia Ann Block, M.D. Maryrose Benkoski Block and Robert Carl Block, M.D. Christine Ann Bloom, M.D. Marylee and Daniel B. Blough Leland S. Blough Sr., M.D.

Mr. and Mrs. Martin J. Calihan

Susan H. and Alan D. Citron

Carol S. and Gary S. Cozen

Thomas Leake Campbell Jr.

Carl D. Citron

The Honorable David W. Craig

Barry M. Brenner, M.D.

Andrea G. Cohen and Rodger D. Citron

Dr. and Mrs. Thomas R. Crain Jr.

‡Gertrude Forman Caplan and Paul S. Caplan, M.D.

Harmar Denny Brereton, M.D. Raymond A. Capone, M.D. Michael Andrew Bresticker

Carol S. Citron and Stanley R. Citron, Esq.

Barbara F. Caroff Edward A. Brethauer Jr., M.D. Katharine J. Carter, M.D. Luiza and Joao Andre Brett William L. Carter, M.D. Judith C. Brillman, M.D. Sally Elizabeth Carty, M.D. Earl James Brink, M.D. Margaret Anne Carver, M.D. Sheryl and Jeffrey Sherwood Broadhurst

Joseph Eugene Casabona

Judith and Earl Bronsteen

Louise Long Cashion and Robert T. Cashion

Susan C. and Robert J. Brooks

Tanyia Harrison Clagette and Vaughn Stewart Clagette, M.D.

Dr. Anthony J. Demetris Dolores and Joseph W. DeNardo

Class of 2004, School of Medicine

Ellen H. and David L. DeNinno ‡Estate of Donald E. Crooks

Connie W. and Bruce T. Cleevely

Dina Denning Robert A. Crown

Patricia Clougherty Virginia and Everette B. Curlee

Gertrude Blumenschein, M.D.

Frank Vincent Castello, M.D.

John F. Cochran, M.D.

George W. Causey Trust

Reed L. Coen

Helen Denny Causey, M.D., and Gilbert B. Causey, M.D.

Michele McKenney and Charles C. Cohen

Mary Ellen and Russell Cersosimo

Leslie Ann Rodnan, M.D., and John B. Cohen, M.D.

William Martin Curtin, M.D. Margaret Shadick Cyert Sue Ann and David J. D’Antoni

Mr. and Mrs. E. Ross Cervick Sandra S. and Richard A. Cohen James M. Chadwick

Tamar and Seth Brufsky

Barbara Richey Chait and Gerald E. Chait

Betty Lou DeSalvo The William John Cully Family

Denise and Brian Cobb

Jill A. Brufsky and Adam Brufsky, M.D., Ph.D.

Katherine B. and Armand DeRose John V. Cuff, M.D.

Kevin Cassidy

Linda C. and Anthony J. Bonidy

Rita S. Deluzio and Vincent Charles Deluzio, Esq.

Albert A. Crimaldi, M.D., Ph.D.

Alvah R. Cass, M.D.

Pamela Bonaventura

Diane D. and Mark C. Deluzio

Robert E. Crawford

‡Peter Cresson

David E. Brougher, M.D.

Sonia and Robert Browning

Ruth Ann and Daniel D. Crawford

Wesley M. Clark

Janet A. and Robert E. Cline

‡Estate of Heidi L. Browning

Beth A. Quill DelConte, M.D., and Anthony DelConte III, M.D. Geraldine W. Dellenback and Dr. Robert J. Dellenback

Maureen Laney and Dan Clarke

Marie S. Chan and William J. Casp, M.D.

Mike Brown

Rose Hammond Delaney, Dr.P.H., and John F. Delaney Jr., M.D., Dr.P.H.

Judy and Joseph S. Crawford

George I. Clendaniel, P.E.

Jeffrey Stuart Brown, M.D.

Thomas Nathan Decker, M.D.

Michael Terrance Creagan, M.D.

John L. Brottem

Thomas H. Brown

Mary Jayne Becker Cramer and William Glenn Cramer

Susan B. Clancy

Richard George Cassoff, M.D.

Michael John Bonidie, M.D.

Beverly DeKosky and Steven T. DeKosky, M.D.

Robert Campana

Charles Kuang Ming Brown, M.D., Ph.D.

Mary Ann and Charles Edward Bogosta

Marguerite M. DeHanis

Sam Covelli

Barry David Brause, M.D.

George R. Coar, M.D.

Nadine E. Bognar

Robert Jude Coury

Sally S. and Donald R. Cameron

Ronda and Mitchell D. Brourman

Frank Joseph Bobick, M.D.

Joseph A. DeCenzo, M.D.

James J. Coyne, M.D.

Gene Louis Brenowitz, M.D.

Janet C. and Pasquale V. DeBlasio

Mary Sheehan Counihan and Dr. Peter J. Counihan

Bonnie J. Cindrich and the Honorable Robert James Cindrich

Lisa J. Rosenberg, M.D., and Neil Aaron Braunstein, M.D.

Patricia Unger Bluestone and Charles D. Bluestone, M.D.

Jill M. Blundon

‡Estate of Helen Lee Wasson Coulter

Lisa M. Cibik, M.D.

Lisa Marie Braughler The Bittner Family

Robert E. Davis, M.D.

Mr. and Mrs. Micky Collins

Margaret and Daniel A. Desko ‡Katherine M. Detre, M.D., Dr.P.H., and Thomas P. Detre, M.D.

James Anthony D’Antonio, M.D.

Deborah Sudatz Detwiler

Dorothy A. Dahll and ‡Hans H. Dahll

Stephanie Buck Dewar, M.D., and James C. Dewar Jr., M.D.

Margit K. Daley

Patricia Ann and James C. Dewar

Carolyn E. Damasio

Douglas P. Dick

Mary L. and Maris Dambekaln

Gregory O. Dick, M.D.

Mildred Danch

‡ before an individual’s name indicates the person is deceased

Katherine Munsch DeSimone, Esq., and David Ralph DeSimone, Esq.

131

DONORS

Gene B. and Robert C. Dickman

DEVELOPMENT

Marianne and John C. DiDonato

Mary Kelly Dudar and Thomas E. Dudar

Joan and John L. Diederich

John M. Duff Jr.

William Stephen Dietrich II, Trustee

Frederick C. Duffy Jr.

Douglas W. Dimitroff, Esq.

Thomas P.J. Duffy

Sally Anne Ehrenwerth and Jan Ehrenwerth, M.D.

Franklin Howard Dines, M.D.

Patricia M. and John K. Duggan Jr. Georgia Duker, Ph.D.

Robert Henry Ehrhart, M.D.

Edward J. Dinnen

Mary Jo and Terry L. Dunlap

Timothy Hammer Eisaman, M.D.

Frank J. Dixon Jr., M.D.

Kevin C. Dunphy

Nicole and Michael Eisenberg

Lee C. Dobler, M.D.

Mary Duplain

Robert L. Eisler, M.D.

Anne Boland Docimo, M.D., and Steven Gerard Docimo, M.D.

Mary Lou and Richard E. Durr

Amy S. Elder

Deborah Detchon Dodds, Esq.

Brenda Grossman Dvorkin and Dr. Daniel Dvorkin

Yvonne G. Elder and Eldon Glenn Elder, M.D.

Pam Dzialowski and Kenneth Joseph Dzialowski, M.D.

Rosalie Elenitsas, M.D.

Patricia K. Eagon, Ph.D.

Jane and John Elliott II

Linda Sawyer Earle and Dr. Martin F. Earle

Lawrence D. Ellis, M.D.

Rhodora J. and John F. Donahue ‡Estate of Emily V. Donaldson

Bijan Eghtesad, M.D. Frederick N. Egler Sr. Karen K. Egorin and Merrill J. Egorin, M.D.

Dr. Robert Elkins

Valerie Donaldson ‡William F. Donaldson Jr., M.D., Trustee, and Jean W. Donaldson James K. Donnell Lowrie C. Ebbert

Lori M. Ellis and Peter Gerard Ellis, M.D.

Diane T. and Mark Dorogy Darlene A. Ebner Susan C. and Roy G. Dorrance III Mary Ruth Sampson Eckman Robert Emmett Dowling, M.D. David Richard Edelstein, M.D.

Michael Emrick

Mr. and Mrs. John D. Edmundson

Dr. Perry H. Engstrom Jr.

Mary Jane E. Edwards and ‡ Richard D. Edwards, Ph.D.

T. Roger Entress, D.M.D.

The Honorable Michael Doyle Irene O. Drews John Robert Duda, M.D.

‡Nancy Arnold Emmerling and ‡ John F. Emmerling, M.D.

Robert Morgan Entwisle III, Esq. Francesmary Modugno and Jeffrey L. Eppinger

Frank Sarris

Marlene and Eugene Epstein

Fr ank and Athena Sarris

Louis Epstein ‡Estate of Jane M. Epstine

Frank Sarris smiles when you call him the “Candyman.” After growing Sarris Candies from a family-sized operation in the basement of his Canonsburg home into a beloved and enduring brand, he’s earned the right to the title. Even after receiving a life-saving kidney transplant in 2002, Mr. Sarris made sure that the people around him had plenty of candy. For the 45 days posttransplant that he spent in UPMC Montefiore, doctors and nurses from all over the hospital were drawn to his room by the smell of chocolate. His family kept him stocked with a steady supply from the company headquarters at the Sarris Chocolate Factory and Ice Cream Parlor, a Canonsburg landmark. “It makes people happy,” he says. “And I knew that more people would come in and check on me if they could pick up a handful of candy on their way out.” Mr. Sarris has nothing but praise for the quality of care he received during this crucial time. “I wouldn’t be here without

the transplant program,” he says. “No doubt about it.” He and his wife, Athena, were so grateful for his second chance that they wanted to give something back. “We asked my doctors, ‘What do you want?’ ” he recounts. “They said they could always use some money. So we gave them $5 million.” This generous gift went to support the Thomas E. Starzl Legacy Endowment, named for legendary transplant pioneer Thomas E. Starzl, M.D., Ph.D. The fund is used for ongoing basic science research to improve the success of transplantation procedures and subsequent patient care. In appreciation, the transplantation clinic on the seventh floor of UPMC Montefiore was renamed the Frank Sarris Outpatient Clinic. The newly remodeled facility was reopened with a chocolate ribbon-cutting ceremony in March 2006. The Sarrises have forged permanent friendships with a number of the medical personnel there. “I’ve just enjoyed getting to know everyone. I’ve met so many nice people,” Mr. Sarris says. At first he was

concerned that he wouldn’t be able to communicate with his transplant specialists in medical jargon. “I can’t talk like they talk, you know. But it turns out that they don’t want to talk about medicine. They want to know about the chocolate business.” Of the many features in the refurbished outpatient clinic, one in particular stands out. The Athena Sarris Café is a free-of-charge coffee station for transplant patients and their families. But this isn’t just any coffee station. Athena planned every detail: two state-of-the-art coffee systems sit on a marble-topped credenza that’s backed by a hand-painted mural of the Greek isles. There’s a choice of no fewer than 12 varieties of coffee, tea, and hot cocoa. “People getting post-transplant care are in and out of that clinic a lot. Some of them don’t have the money to pay $3 or $4 every time they want a cup of coffee,” says Mr. Sarris. “And even sick people — especially sick people — need to take time out for a treat.”

David J. Erikson Jr., M.D. Eric R. Erlbaum, M.D. Rev. William D. Erving Judith E. Eshelman Clifford Joseph Eskey, M.D. Kenneth L. Euler, Ph.D. Sally A. Lysinger Evans and Dr. Terry Lynn Evans Mr. and Mrs. Thomas M. Evans Jr. James Richard Eynon, M.D. Augie K. Fabella II Christopher Neal Faber, M.D. Lillian F. Fabry and Edward Irwin Fabry, M.D. Gloria L. and Michael Fader Nellie C. Fain Ralph A. Falbo Jr. Jacob Chin-Gong Fan, M.D. Mary Snider Farley and Emerson D. Farley Jr., M.D. Sally St. John Faulkner and James W. Faulkner III

‡ before an individual’s name indicates the person is deceased

133

134

DONORS

Michael Gregory Faust, M.D.

Alice B. Fox

George A. Fechter

Jane K. France

Family and Friends of Nancy Porada Giesmann

Jennifer Grandis, M.D., and Donald J. Grandis, M.D.

Deborah S. Feckett-Rhode

Patricia Ann Francioni

Richard Giffhorn

Marie A. and Robert T. Gray

John T. Fenner

Mr. and Mrs. Tim Freer

Susan Marie Gilbert

Kathryn and Vincent C. Gray

Carol D. Hamilton and S. Sutton Hamilton III, M.D.

Joseph Ferens

Michelle Gray Freyvogel and John A. Freyvogel

Lesley Irene Gilbertson, M.D.

Patricia L. and Daniel P. Grealish

Mary and James S. Hamilton

Faith E. Gill and Thomas J. Gill III, M.D.

Thomas B. Grealish

Robert W. Hamilton, M.D.

Richard B. Greaney, M.D.

Cary Lee Hamlin, M.D.

Richard Mark Ginsburg, M.D.

Carolyn E. and Adam Green

Alistair M. Hanna

Joan Boby Gitlin, M.D.

Dana and Richard Green

J. Matthew Glascock, M.D.

Joan Kaplan Green and Robert M. Green, M.D.

Mary Anne D. and Howard W. Hanna III

Dennis Donald Ferguson, M.D. Mary Anne Ferguson

Michelle V. and Dr. David M. Friedland

Rita N. and James M. Ferguson II Robert Howard Ferguson, M.D. Lawrence Ferlan, M.D. Emilio A. Fernandez

Carolyn Fine Friedman and Jeremiah Friedman Cynthia Aberman Friedman Mark Richard Friedman, M.D.

Louis Glasser, M.D. ‡Marcia Swartz Glosser, M.D., and Daniel Glosser

Arlene Butera Ferrante

Charlene A. and John P. Friel

Mary Ellen and William A. Ferri Jr., M.D.

Mr. and Mrs. Thomas P. Frizzell

Robert Joel Gluckman, M.D.

John J. Fromen Jr., Esq.

Lee Glunt and J. Roger Glunt

Hilda Pang Fu and Freddie H.K. Fu, M.D.

James E. Goddard Jr., M.D.

Dr. Robert Louis Ferris Dr. Marcia Ruth McInnes and Rocco A. Fiato

Jack Greenberg, M.D. Diane L. and John R. Greenwood

Barbara J. and Robert W. Hannan

Betty and Rodger Hess

Mary Jane and Carl G. Grefenstette

Lori Z. and Thomas M. Hardiman

Patricia Bednarik and Rock A. Heyman, M.D.

Sher Leigh and Gary Grelick

Mary Ann Harding Marion and Charles H. Harff

John B. Hibbs Jr., M.D.

Inger Grenvik and Ake Grenvik, M.D., Ph.D.

Susan B. and David H. Hicks

Margaret M. Hill and John B. Hill, M.D.

John L. Harrington, M.D.

Beth A. and Gregory S. Goetzman

Betty W. Harris and Barry C. Harris, M.D.

Peggy Sloan Hill

Dietrich M. Gross Robert Scott Furman, M.D. Jill Fusaro

Karen Marie Kreiling, M.D., and Paul E. Golden

Franco Harris

Mary L. and Thomas M. Hill

Karen Fisher Harris, M.D. Rosanne and Anthony M. Harrison

Audrey Hillman Hilliard and Thomas J. Hilliard Jr.

C. Scott Harrison, M.D.

Elsie and Henry L. Hillman

Georgia V. Harrison

Carolyn and Gerald Hindy

Mahnaz Harrison

Stanley A. Hirsch, M.D.

Ross Harrison

Daniel J. Hirsen, M.D.

Theresa Kadunce Flatley and Lawrence Edward Flatley Deborah Flaus Jeffrey E. Flynn Dr. Richard N. Fogoros Carol Ann Foley and Edward L. Foley, M.D.

Lisa Gallagher

Sally Weigler Golden and Thomas B. Golden Jr.

James R. Grundtisch

Susan Pachtman Golden and J.P. Goldman

The Lawrence N. Gumberg Family

Patrick A. Gallagher

Dana Marie Grzybicki

Stanley H. Goldmann Mr. and Mrs. Don J. Gunther

Kim M. Galle

Jill K. and Alan S. Goldsmith Nilakshi Gupta, M.D.

Christopher M. Gallea

Linda L. and F. Lynn Foltz

Milton K. Harsh

William A. Hite

P. Brennan Hart

Kathleen A. Ho

Marissa and Burt Hartington

John Andrew Hodak, M.D.

Xuemei Yuan and Dr. Takanori Hashimoto

Ulton G. Hodgin Jr., M.D.

Dale R. Hoffman

Susan G. Guttman

Peggy Braasch Hasley, M.D., and Stephen Kinneman Hasley, M.D.

Robert E. Guyo

Caryn Hasselbring, M.D.

Joel Edward Haas, M.D.

Harold Wayne Hatten Jr., M.D.

Lillian H. Goldsmith Linda J. and R.P. Gustafson

Connie and Thomas R. Galloway Sr.

Edward M. Goldston Richard P. Gustafson Jr.

Julian Gammon

Alvin I. Goldstone, M.D. Thomas Arthur Gustin, M.D.

Chip Ganassi

Gregg Lincoln Goldstrohm, M.D. Sara and Alan R. Guttman

Sandra J. and Alvaro Garcia-Tunon

Barney C. Guttman Harry W. Gardner, M.D. Dr. Rebecca Garrett Ruth C. and Walter Gasiorowski Jr. Mary George Gast and Dr. Robert C. Gast Christopher C. Gates, M.D.

Dennis F. Hoeffler, M.D.

William Gomez, M.D. Ellen R. Goodman Michael Louis Goodman, M.D. Sandra Green Goodman and Lee S. Goodman Martha Hudson Goodrich Allen Michael Goorin, M.D.

Ellen Geller and David A. Geller, M.D.

Marianne Gorcsan and John Gorcsan III, M.D.

Marne B. Geller and Dr. Peter B. Geller

Harold E. Gordon, M.D. Nanette and Ira Gordon

Michael Gelman R.M. Gordon Jr.

Susan Follansbee and William P. Follansbee, M.D.

Heidi Hill and Dr. Thomas J. Hill

Ruth A. and Christopher J. Groven

Marcia and Stanley R. Gumberg

Stephanie and Thomas T. Flannery

Tracy G. and J. Craig Hill

Richard L. Grossman

John Gallagher

Lauren S. Flannery

Friends of Wendy Herz

Carl William Groppe Jr., M.D.

Audrey Hillman Fisher and Timothy O. Fisher

Rozanne E. and Edward J. Flammer

Susan S. Hershenson and Lee M. Hershenson, M.D.

Mary Forbes Hanna and Dwight C. Hanna III, M.D.

Mary Ondina Martinez and Michael D. Goetz

Virginia M. and Richard L. Fischer

George M. Fitting, M.D.

Dwight E. Heron, M.D.

Beth A. Fung and John J. Fung, M.D., Ph.D.

Lisa Gabrieli

David R. Fitzsimmons

Georgia C. and Robert Michael Hernandez

Roger H. Griffin, M.D.

Jennifer J. and Donald P. Fusilli

Jacqueline and Guy W. Fiske

Harriet L. Herberman and Ronald B. Herberman, M.D.

Robert T. Harper

Janis W. Fink and Mitchell P. Fink, M.D.

Nina Fisher

Sarah J. and C. Talbot Heppenstall Jr.

Gordon Albert Gress, M.D.

Sheila R. and Milton Fine

Lilian H. Fisher

Roberta E. Bauer Henkel, M.D.

Carlotta Mollica Goetz and John Goetz

John Joseph Godleski, M.D.

Richard J. Finder, M.D.

Ann Yeager Fisher and Henry Fisher

Bernard J. Hendrzak

The Family of John Fulmer

Robert J. Fierle

Edith Hall Fisher and James A. Fisher

Heidi and Robert E. Heltzel

Duilla Puckett Harkins and Paul Duane Harkins, M.D.

Frank B. Fuhrer Jr. Dr. Margaret McConnell Figgins and David F. Figgins

Henry R. Halperin ‡Bernard M. Halpern, Trustee

DEVELOPMENT

Genge Family

Mr. and Mrs. Thomas S. Haas

‡Estate of Lucille W. Hauber

Christy and Robert G. Hofmann II Joyce Holl Kathleen N. and Lawrence P. Holleran Dr. Jeffrey O. Hollinger

Mr. and Mrs. George A. Hackett

Dennis Lynn Headings, M.D.

Katherine and W. Penn Hackney

Susie G. and Erle R. Heaton

Martha Braun Holmes and Robert Bruce Holmes, M.D.

Mary and Kahle Hahn

Brockton J. Hefflin, M.D.

Sy M. Holzer

Jennifer L. Plombon and Stephen J. Haines, M.D.

Ruth Champlin Hefflin and ‡ Charles Hefflin, M.D.

Elmer J. Holzinger, M.D.

Lynn Hudson Hale and Wayne Andrew Hale, M.D.

‡Eric H. Heinemann

Stephen Randall Holzman, M.D.

Edward William Heinle, M.D.

Nancy Solimine Honbo and Ken Shoji Honbo, M.D.

Jacqueline Haley

Gregory C. Heins

Mark R. Hoover

Vicki B. Hall

Dr. Jules Heisler

Thomas Horan

Daniel George Haller, M.D.

Dr. William H. Helfand

Thomas O. Hornstein

Shadely and Robert A. Gordon ‡Estate of William Harrison Genge, Trustee

Katie and Thomas P. Gordon

Kenneth A. Foon, M.D.

Anthony Fernardo Gentile, M.D.

Franklyn R. Gorell

Henri R. Ford, M.D.

Trudy Elbaum Gottesman and Robert William Gottesman

Isabel Foster and Lee Byron Foster II

Ellen R. Gerszten and Dr. Enrique Gerszten

Walter Daniel Foster, M.D.

Amir Ghaznavi

Marjorie B. Haller Kamillah L. Hallmon and William Nicholas Hallmon Jr., M.D.

‡ before an individual’s name indicates the person is deceased

‡Theodore R. Helmbold, M.D. Joan L. Helsel and Jay D. Helsel, Ed.D.

Joel Horowitz, M.D. Robert F. Horsch, M.D. Mary Jo and Robert P. Horvat

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Joseph Stephen Horvath, M.D.

Gerald Samuel Johnston, M.D.

Susan W. and Michael W.D. Howell

James R. Johnston, M.D.

Michael Hrabovsky Joan R. Huber

Marilyn S. Johnstone and Graham Findlay Johnstone, M.D.

Laura J. Huch-Kerckhoff

Davis Benton Jones III, M.D.

Ruth Anne and Thomas J. Huckestein

Dorothy F. and Harley F. Jones Jr. Gregory Baldwin Jordan, Esq.

John Steven Karduck, M.D.

Julie and Daniel Graham Hudak

Marsha B. and Robert Karp

Howard L. Hudson, M.D.

Lori Sobel Jubelirer and Brad Allen Jubelirer, M.D.

Thomas Edward Hughes Jr., M.D.

Kevin David Judy, M.D.

Ed Huling

Renée T. Juhl, Pharm.D., and Randy P. Juhl, Ph.D.

Francine Stein Kasoff and Samuel S. Kasoff, M.D.

Warren T. Kable Jr., M.D.

Christina L. and Brian J. Kassalen

Ruby K. Kang and James D. Kang, M.D. David N. Kaplan Janet L. and Morris J. Kaplan

Judith Hoffman Kasdan and Richard Bruce Kasdan, M.D.

Joan A.B. Hulm Aura R. Hulme

Patricia J. and William Kassling

A. Richard Kacin Fannie E. and Quennon A. Hundley

Neil Matthew Kassman, M.D.

‡Constance A. Kalberkamp Richard A. Hundley Carolyn Anne Maue and Bryan John Hunt

Irene Getzie Kane and Kevin M. Kane, M.D.

Shalom Kalnicki, M.D.

Julia Ann Katarincic, M.D.

Gayle Louise Tissue and Yiannis Kaloyeropoulos

George W. Katter, M.D.

Donald B. Kamerer, M.D.

Diane C. Katz

David Leland Katz, M.D.

Stephen Warren Hunt III, Ph.D. James C. Huntington Dennis J. Hurwitz, M.D.

Elaine Scheiner Kamil, M.D., and Ivan Kamil, M.D.

Dr. John Hyland

Daniel Kamin

Karen and Jon M. Ibella

Hannah Kamin

Calvin Theodore Iida, M.D., Ph.D.

Elizabeth Clew Kampmeinert and Robert W. Kampmeinert

Sally M. Imbriglia

‡Helen B. Katz Beryl Voigt and John S.L. Katz Wallis F. Katz and Marshall P. Katz Howard Elliot Katzman, M.D. Matthew B. Kaufman

Rhonda L. Iserman and Jordan Charles Iserman, M.D. Arnold Palmer with Mulligan

Dr. Mark Robert Izzo Irene S. Jackson and James Fraser Jackson, M.D.

Arnold Palmer

The Stamm Jackson Family

A white-haired man is standing on his back deck, golf club in hand. Just a few feet away, his dog is literally dancing with anticipation. Suddenly the club goes back and then down again in a fluid, seamless motion that is completely inseparable from the man himself. The swing connects — and a grimy yellow tennis ball goes flying into the air. Arnold Palmer’s 6-year-old Labrador retriever, Mulligan, immediately gives chase, blissfully oblivious to the number of sports journalists who have expended gallons of ink trying to describe the exquisite beauty of the golf swing propelling his daily game of fetch. While Mulligan may be unaware of his luck, Mr. Palmer is quick to acknowledge his own good fortune as a prostate cancer survivor. “I knew something was wrong at the time,” he said of his 1997 diagnosis, “but no one wants to hear that they have cancer.” Unfortunately, however, his recovery following surgery and radiation was sadly colored by his wife Winnie’s diagnosis of peritoneal carcinoma. Her cancer proved fatal in 1999.

Timothy D. Jacob, M.D. David Jacobs, M.D. Jean Lynn Jacobs and Samuel A. Jacobs, M.D. Sandra L. Jaeger and Edward A. Jaeger, M.D. Cecelia S. and Frank G. Jaworowski Marsha E. and James Jay Rosemarie Conte Jew and Edward Walter Jew Jr. Paul Jewell Joan Johnson and David Sterling Johnson, M.D. Eric Johnson Farris Thomas Johnson Jr., M.D. LaVonne Corley Johnson and Glen R. Johnson Janis C. Johnson and Jonas T. Johnson, M.D. Sally and Lewis Johnson Susan J. Johnson David Eugene Johnston, M.D.

‡ before an individual’s name indicates the person is deceased

“I’ve had to deal with cancer a lot in my life,” says Mr. Palmer. He had already witnessed the emotional and physical tolls of the disease firsthand when his daughter, Amy Saunders, discovered she had breast cancer in 1990. A 32-year-old mother of four at the time of her diagnosis, Amy fought and survived. (On the morning this photo was taken, Amy’s daughter, Katie, had just given birth to a baby girl, making her a grandmother and Mr. Palmer a first-time great-grandparent.) Even before his family’s experiences, Mr. Palmer had served as benefactor to a number of cancer-related causes and funds. Thanks to his recent generosity to the University of Pittsburgh, the University of Pittsburgh Cancer Institute (UPCI) is now home to the Arnold Palmer Endowed Chair in Cancer Prevention. This $2 million gift has enabled UPCI to recruit Emanuela Taioli, M.D., Ph.D., an internationally recognized hematologist / oncologist and epidemiologist, to head a new UPCI division devoted to cancer risk and prevention.

“I’m encouraged by many things that are happening that are leading toward the eventual cure or elimination of cancer from our lives,” says Mr. Palmer. “There are a lot of developments out there. So one thing I’m particularly interested in is the flow of communication within the medical community. What I try to support and encourage is better communication among hospitals and doctors and researchers. “But on an individual level,” he continues, “the best advice you can give anyone is to pay attention. Early detection is key. Take your general physical every year. Go to your doctor in the meantime if you think anything is the least bit wrong.” “You have to go,” adds Mr. Palmer’s administrative assistant of 40 years, Doc Giffin. “I survived bladder cancer more than 20 years ago because it was detected early enough. I had to have surgery and some chemo, but I’m OK now.” “He didn’t even take a physical until I forced him to,” Mr. Palmer says, turning to his longtime friend. “And I’m glad I did.”

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DONORS

Dorothy P. and Ralph W. Kaufmann

DEVELOPMENT

Charles Dietrick Lamade, M.D.

Mr. and Mrs. Anthony W. Liberati Alan David Lichstrahl, M.D.

Dr. Daphne Bicket and John Charles Lynn

Susan H. and Christopher Stephen Martin

Neal David Kohatsu, M.D.

Paula Marie Jernigan, M.D., and Andrew David Laman, M.D.

Jeffrey L. Lignelli

Charles I. Lytle II

Traci M. Kohl, M.D.

Paul David Laman, M.D.

Virginia M. Martin and William T. Martin, M.D.

Robert David Lille, M.D.

Margaret Michele LaManna, M.D.

David A. Keilman, M.D.

Arlene E. Kokales and John George Kokales, M.D.

William N. Macartney III and Samuel J. Simon

Evelyn D. Lim and Felixberto D. Lim, M.D.

James Rudolph Macielak, M.D.

William Leroy Martin, M.D.

Dale B. Keller

Lois E. Kolb

Stewart L. Lancaster, M.D.

Brian Limbach

Josephine B. Martinez

Charles Francis Kelley Jr., M.D.

Susan Pauline Kondziolka and Douglas S. Kondziolka, M.D.

Marjorie L. Maclachlan and William W.G. Maclachlan, M.D.

Michael Jay Landay, M.D.

Linda Sue and Eric Limbach

Lisa R. and Anthony P. Kaverman

Denise M. Kochanek and Patrick M. Kochanek, M.D.

Christine Kealey Patricia A. Keefe and Robert Emmett Keefe Jr., M.D.

James P. Kelley

Lee Ann and Richard F. Lamb

Stephen Ellis Landay, M.D.

Debra and Kurt Limbach

Sylvia Ziff Landay

Carol and Mark Limbach

Joseph Michael Kontra, M.D. Karen Dunn Kelley and Joseph L. Kelley III, M.D.

Thomas R. Kopf

David M. Kelly

Frank Kopfer

James E. Kelly, Esq.

Charles E. Kovar, M.D.

Nancy and Donald R. Kennedy

Ronald L. Krall, M.D.

Lisa Kent and Edward Francis Kent Jr., M.D.

Lisa R. Kranc

Susan Lynne Kerr, M.D.

Florence Kaufman Krell

Helen Wettach Lang

Thomas F. Limberis

Ann Marie Langerholc

Judith and Ronald Linaburg

Carol Larson

Carolyn Kay Lincoln, Ph.D.

Ralph Edward Lattanzio John Francis Kraus, M.D. Richard R. Laughner Jr. ‡Ignatius C. Laux Norman N. Kresh, M.D.

Gauri J. Kiefer, M.D., and Jan F. Kiefer

Susan Louise Krieg, M.D.

John Stephen Lazo, Ph.D.

‡Estate of Barbara Hargrave Kielman Dorothy W. Killius Seung Lee and Jang Hae Kim, Ph.D. L. Robert Kimball

Mark R. Leadbetter, M.D. Richard P. Krieger Stanley Lechner Jocelyn and Daniel Krifcher Emanuel Krifcher, M.D. Ashok S. Krishnamurthy

Pamela J. and D. Scott Kroh Freya E. Hory Lee, Ph.D., and William Lee, M.D.

Nancy J. and Edward M. Krokosky

Robin Kinney

Jennifer and Keith D. Kronk

Susan Rita Kinsey, Ph.D.

Mary Beth and Christopher Leech

Tanya M. and Eugene W. Klaber

Laura Penrod Kronk and Claude F. Kronk

Edmond S. Klausner, M.D.

Mary Louise Kubacki

Paul E. Lego, Trustee, and Ann Sepety Lego

Kathryn U. and Cary H. Klein

Connie M. and Charles T. Kucera Jr.

Ruth Ann Eisner Klein and Eugene J. Klein

Beth E. Kuhn

Louisa Barnhart, M.D., and Michael David Klein, M.D.

Michael R. Kuhn

Anne Marie Czyz-Klemens, D.M.D., and Lee James Klemens, M.D.

Marrick Lee Kukin, M.D. Lawrence Michael Kulla, M.D. Frank Alfred Kunkel, M.D.

Barbara Kleyman and Thomas Ralph Kleyman, M.D. Esther Klionsky and Dr. Bernard Klionsky

James Vachon Kunkel, M.D. ‡Virginia Kunkle

W.P. Andrew Lee, M.D.

Robert W. Leibold, M.D. Nathalie and Mario Lemieux Peter Leventis Robert C. Levin Sally M. Levin Ruth E. Levine and Arthur S. Levine, M.D. Claire Berland Levine and Lawrence Levine

Olabisi Olajuyin Kuye, M.D.

Lois Galtz Levy

Linda B. Kuzon and William M. Kuzon, M.D., Ph.D.

Stanley Hurwick Levy, M.D.

Tim Knight Julia W. Knoell

Clarence E. Kylander, M.D.

William L. Knappenberger Jr., M.D.

William H. Knoell David John Kobaly, M.D. Lindsay Rae Wigginton and Christopher H. Koch

Jennifer Ann LaFemina

Seena Goldman Lewine and Robert A. Lewine, M.D. ‡Edward J. Lewis

Michael Scott LaFrankie

Elsie Y. Lewis

Robert W. Lahey

Ellen S. Lewis and ‡ Robert E. Lewis, M.D.

Patrick Laine Julia and Scott A. Lewis

Julie A. Koch Valerie R. Koch Wayne Martin Koch, M.D.

Brian T. Laird Gary B. Lake, M.D. Margaret S. Lally, M.D.

Carolyn and Joseph Massaro

Helen Mahaj and Vincent R. Mahaj, M.D.

Sharon Malley

Gordon Lisker

Stephanie F. Mallinger and Dr. Bernard Mallinger

Chau-Ching Liu, M.D., Ph.D.

David E. Malehorn, Ph.D.

Ruth Snyder Masters, M.D. Micheal G. Mastry, M.D.

Barbara Barnes, M.D., M.S., and Richard Ley Luyuan Li, Ph.D.

Rachel Joy Givelber, M.D., and Michael Arthur Mathier, M.D. ‡Estate of Norman Gardner Mathieson, M.D. Helen Fricke Mathieson

Paula M. Lockhart

Miriam G. Blitzer, Ph.D., and David Bruce Mallott, M.D.

David Michael Matter

Penny Berkowitz Loeb, M.D., and John Maxwell Loeb, M.D.

David J. Malone

Carol Matthews and Robert G. Matthews, M.D.

Bridget K. Loftus

Linda R. and James R. Malone

Gerald F. Loftus, M.D.

Carole J. Mankin and Henry J. Mankin, M.D.

Terri and Timothy J. Logan Kathleen M. Lee and Robert E. Lee, M.D.

Mary Rita King

Jeffrey B. Kuhn

Myrna and Mark E. Mason

Mary Beth Maguire and Richard Robert Maguire, M.D.

Shelley and Jeffrey M. Lipton

Ilda G. and Charles R. Lee

A. Alice Chauss Kindling, Trustee

George Jerome Magovern Jr., M.D.

John Francis Mahoney, M.D.

Byeong Chel Lee, Ph.D. Patricia Dowley Kroboth, Ph.D., and Frank J. Kroboth, M.D.

Gail Reede Jones, M.D., and Jesse Mason

Karen Wichmann Lipman and Sidney Philip Lipman, M.D.

Alberta M. Lee

Taylor Kincaid

Maggie Hardy Magerko

Aleen Allsop Mathews Regina Lasko

Roy Eugene Kerry, M.D.

Rev. Warren K. Martin

David S. Matthews, M.D. John Thomas Matthews III, M.D. K.I. Maull, M.D.

Richard M. Mann, M.D. Anna Lokshin, Ph.D.

Jane B. Maxwell Geeta Sehgal Mantha

James John Lombardi Venkat Ramana Rao Mantha Linda M. Cadaret, M.D., and Barry London, M.D., Ph.D.

Joseph A. Marasco Jr., M.D.

Mary and Ronald E. Long

Harold K. Marder, M.D.

F. Joseph Loughrey

Dorothy Maritime

Diana Love and J. Robert Love, M.D., M.Sc.

Joan and James J. Markovich

Jane V. and Howard M. Love

Alvin Markovitz, M.D.

Mignon and Waldemar J. Love

Ellen Marks

Mark Robert Lovell, Ph.D.

Stanley M. Marks, M.D.

Charles U. Lowe, M.D.

Robert S. Markwell

Donna L.B. Lowry, M.D., and David Warren Lowry, M.D.

John E. Marlow, M.D.

William Howard Markle

Roma Vega May and James Brian May David Alan Maybee, M.D. Joan Marie Lakoski, Ph.D., and Paul Mayercik Rebekah Mazariegos and George V. Mazariegos, M.D. Kristin Elisabeth Haber, M.D., and Andrew Malcolm McAlpin, M.D. Frederick S. McAlpine, M.D. Clyde Edward McAuley, M.D. Kathleen M. McCabe Gray McCalley Jr.

Mr. and Mrs. Albert E. Maroone Jackson Howard McCarter, M.D.

Donald J. Lowry, M.D. Lucine O’Brien Marous and John Charles Marous Jr.

Thomas E. McCarthy, M.D.

Helen B. and Curtis R. Marquard

Berrylin J. Ferguson, M.D., and Kenneth McCarty, M.D., Ph.D.

Annette M. and Gary Luchini

Marian K. Marquis, M.D., and William Edward Marquis

Kay E. and James E. McClaine

Christine Luketich and James D. Luketich, M.D.

Barbara F. and Bernard S. Mars

Bruce A. McClane, Ph.D.

Lisa Mars

A. Gregory McClure, M.D.

Amy Krueger Marsh and F. Joseph Marsh

Kathryn Kraus McClure, M.D.

Tracey and Robert Marsh

Leslie Merrill McCombs

Marie C. and William M. Lowry ‡Miriam Elrich Lubow and ‡ Harry Lubow, M.D.

Mr. and Mrs. Thomas C. Lund Julianne M. Lunsford and L. Dade Lunsford, M.D.

George R. McCollum, M.D.

Simone and Scott F. Lutgert ‡William T. Marsh

Kambra B. McConnel

James M. Lynch, M.D. Maxine L. Marshall

Anne and William O. McConnel

Karyn Greb Lynch Samuel S. Lyness, M.D.

‡ before an individual’s name indicates the person is deceased

‡Thomas Marshall, M.D., Trustee, and Joan Marshall

Eileen A. and Thomas A. McConomy

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140

Jennifer and Christopher McCrady Madelaine and L. Colvin McCrady

Amy Affleck Meyer and Dr. Mark W. Meyer

Frances Minno, Esq., and Alexander M. Minno, M.D.

Andrea K. and Gerald M. McCutcheon

Ann R. and Richard B. Meyer

Ramesh A. Mirchandani

Mr. and Mrs. Joseph F. McDonough

Kimberly Meyers and Dr. James H. Meyers

James P. Miscoll Janet Lynn Misko

John R. McGinley Jr. Joseph Thomas Michael, M.D. Janice and Dennis McGlone Jane Love McGraw

Lois G. Michaels and Milton Meyer Michaels, M.D.

Ann M. McGuinn and Martin G. McGuinn

Mary Ann Wolak Michelis, M.D.

Joan W. and Thomas E. Mistler Nicholas C. Mitchell Sr. Robin E. Mockenhaupt Thomas Anthony Modesto, M.D.

John Miclot Kristi and Tom McGuire

Lester R. Mohler, M.D. Philip J. Migliore, M.D.

Christine Louise McHenry, M.D.

Kim and Jeffrey L. Moody Katherina A. Miller Trust

Regis William McHugh, M.D.

Bernadette R. Moore Russell P. and Margaret J. Miller Trust

Timothy A. McHugh, M.D.

Elizabeth E. and John A. Moore Cedric B. Miller, M.D.

Douglas R. McIlwain David McKamish

Gwen D. Miller and ‡ Felix H. Miller, M.D.

Patsy and Donald McKinney

Nancy L. and James C. Miller

Peggy Thomas McKnight and Stephen Hayward McKnight A.T. McLaughlin Julie S. McLaughlin and Mark R. McLaughlin, M.D.

Dr. Mark D. Miller ‡Margaret Speirs Miller and ‡Russell P. Miller

Yuan Chang, M.D., and Patrick S. Moore, M.D., M.P.H. Mary Jane DeYoung and Robert Y. Moore, M.D., Ph.D. Delynne J. Myers, M.D., and John Jefferson Moossy, M.D.

Timothy A. Miller, M.D.

Devra Lee Davis, Ph.D., and Richard D. Morgenstern, Ph.D.

William Paul Miller, M.D.

Paul Morigi

Ken Milligan

Natalie Chetlin Moritz, Esq., and J. Kenneth Moritz, Esq.

Mary Lou Schweinberg McLaughlin Martha H. McLaurin Kenyon Milligan Deborah D. McMahon, M.D.

Michael J. Moritz, M.D.

‡Margaret M. McMaster Pearl G. McNall, M.D. Susan, Alan, and Carl Citron, with Dr. Kenneth Lee

Beverly McNamara Kathleen Welsh McSorley and David McSorley

The Family of Jane Citron

Mary L. Means, Ph.D.

Professional cook, writer, teacher, traveler: the rich, creative career of culinary arts expert Jane Citron was far too multifaceted to be described by any single label. When she died on December 15, 2006, after a six-year battle with colon cancer, her passing was mourned by countless friends and readers who would miss the rare balance of passion and common sense with which Mrs. Citron approached both food and life. As a tribute to Jane Citron, her family, including her husband, Carl; son Alan and his wife, Susan; son Stanley and his wife, Carol; and son Rodger and his wife, Andrea Cohen, established the Citron Family Endowed Fund in Honor of Dr. Kenneth Lee. The goal of the fund is to raise $2 million to support research on colorectal cancer and its prevention, as well as clinical programs that support excellence in patient care. The Citrons are quick to point out that the fund was developed before Jane’s death and that it was her idea to dedicate it to Kenneth K.W. Lee, M.D., associate professor of surgery and her primary

Daniel A. Medalie, M.D. Anne R. Medsger and Thomas A. Medsger Jr., M.D. Dr. Gerald Richard Medwick Mrs. Withrow W. Meeker Alexis Michelle Megaludis, M.D. Ronald George Mehok, M.D. Linda S. Serody and Prof. Alan Meisel Stephanie Wolk Mendel Emily Solomon Mendelson Janice Annette Mendelson, M.D. Barbara S. Mendlowitz Karen A. Mercaldo Vicky Merryman Gregory Edward Merti, M.D. Judith M. Metzger and Dr. James A. Metzger Judith Metzger and Dr. Clyde C. Metzger

‡ before an individual’s name indicates the person is deceased

physician throughout her illness. “She blessed the fund,” says Alan, “and she loved Ken. The fact that he was so exceptional has helped us all fight through the inertia of this disease.” It’s clear that the Citron family’s admiration runs both ways. Dr. Lee remembers Mrs. Citron as a “glowing” woman who, even while struggling with cancer, found the energy to form personal connections with the caregivers she encountered during her treatments. “I first met the Citron family when Mrs. Citron came to see me. And I can see her in all of them,” says Dr. Lee. “What they are doing, their sheer commitment, is extraordinary.” “Dr. Lee was always caring and compassionate with all of us,” says Carl Citron, “and he was always available for my wife. He would answer your questions and never make you feel rushed.” Carl recalls, for example, a time when Jane experienced a post-surgical crisis that required immediate additional surgery. “It was after 1:00 a.m., but Dr. Lee came back and stayed there all night working to save her. That’s the kind of doctor he is.” name an individual’s ‡ before indicates the person is deceased

In May 2007, the Citrons organized and hosted a highly successful dinner event, “Cooking Up A Cure,” at Oakmont Country Club; it was attended by 270 people. The family is developing a number of ideas for future fund-raising activities, including the release of a cookbook of recipes written and compiled by Jane before her death. “We hope to continue raising enthusiasm for the fund so we can raise awareness about colon cancer,” says Susan. “We realize that there are so many people suffering from this disease. It’s the second leading cause of cancer death in the United States. We know what it’s like to be that family, waiting and eager and nervous and scared,” she says. “We just want to help other people who are going through the same thing.” Alan adds, “We just couldn’t believe that nothing is being done about this on a local basis, particularly since we’re so fortunate to have such a world-class cancer institute in the area. So we decided to do something.”

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DONORS

DEVELOPMENT

Gary Morrell

Teresa Nolan

Mark E. Pasquerilla, Trustee

William Richard Poller, M.D.

Melissa F. and Robert M. Reed II

Robert Rosenkranz

Constance T. and Bruce W. Morrison

Anne L. and James E. Noland

Bruce Edward Pollock, M.D.

Candy and John C. Regan

Louisa S. Rosenthal

BeeJee and Perry Morrison

Barbara Ann V. and Stephen G. Noon

Maya S. Patel and Subodh G. Patel, M.D.

Gary Poltorak

John F. Rehak

Cynthia L. Roth

Anne G. and Scott W. Reid

Jay D. Roth

Barbara G. Poolos and C. James Poolos, M.D.

Fae A. Reilly and William M. Reilly Jr., M.D.

Robert Jay Roth, D.M.D., M.D.

Mary Ann and Karl W. Poorbaugh

Scott Curtis Reinhart, M.D.

Paul Sidney Porter, M.D.

John P. Reisman

Kirk Posmanture

Lauren B. Resnick, Ed.D., and Daniel P. Resnick, Ph.D.

Faye and Dennis D. Mosco William S. Moskovitz, M.D.

Marjorie J. Nord and Roland E. Nord, M.D.

Barry David Moskowitz, M.D. Mr. and Mrs. Greg Norman

Brian W. Patten Tammy A. and James S. Patterson Suzanne O. Paul and Richard Paul, M.D.

Mike Moulton Joseph F. Novak, M.D. Donald M. Mrvos, M.D. Harry Matthew Null, M.D. Lawrence M. Mulhern, M.D. Thomas H. O’Brien, Trustee Nancy M. Munn Mr. and Mrs. Gerald Duffy O’Connor Ann and Charles Munson

Robert A. Paul, Trustee, and Donna Paul

‡Herbert P. Pontzer, M.D.

‡Hercules Paxinos Dorothy J. Peck Payne and Fred J. Payne, M.D.

Helen MacMurdo Posner and Henry Posner Jr.

Brian J. O’Mara

Philip C. Pretter, M.D.

Randy Reynolds, Esq.

Bruno M. Peault, Ph.D.

Meredith and Peter Rugg ‡Estate of Margaret Townsend Price

Laure Croisille Peault, M.D., Ph.D.

David Lee Obley, M.D.

Robert Louis Peel, M.D.

Barbara Myers and Eugene N. Myers, M.D.

Janet Marie Ocel, Ph.D.

Dr. and Mrs. Andrew Bertram Peitzman

Patricia C. and Vincent J. Quatrini Jr.

Lou Rene Myers and ‡ Gilbert Bradford Myers, M.D.

Margaret Hall Offenbach and Jack Offenbach

Renée M. Pekor

Mr. and Mrs. J. Joseph Myers

Yumiko Oishi and Masaki Oishi, M.D.

Donna Pellegrini, M.D., and Ronald V. Pellegrini, M.D.

Jessica R. Myers

Joanne R. Oleck, M.D.

Cathy J. and John H. Pelusi Jr.

Margaret A. Myers Faith and Nelson Myers Barbara Deutsch Nadel and Alan Marc Nadel, M.D.

John Scott Oehrle, M.D.

Charlotte Oliver Lois A. Pounds Oliver, M.D. Christine J. Olson Phyllis J. Olson M. Vernon Ordiway Ellen Meredith Ormond, Ph.D.

Mary J. Nagel and John Robert Nagel, M.D.

George M. Orr, M.D.

Dr. Masahiko Nakano

Mark B. Orringer, M.D.

Cathy Nalesnik and Michael A. Nalesnik, M.D.

John Edward Ott, M.D.

James V. Napier

Kimberly E. Rubash and Harry Edward Rubash, M.D.

Jorge D. Reyes, M.D.

Saundra K. and Eugene J. O’Sullivan

Grace A. Houghton and John Lewis Myers

Norma and Duane Rubash

Paul A. Prendergast

Maureen and James Murphy Norma Jane Duncan Musgrave and Ross H. Musgrave, M.D.

James Caldwell Rex Jr., M.D.

James F. O’Keefe Jr., M.D. Mary and James L. Murdy

Janine M. Pagano Mr. and Mrs. Richard A. Pagliari

Pennsylvania State Police Troop M Faith R. and Barry L. Pennypacker Matt Perachi David Hirsch Perlmutter, M.D.

Diane D. and Clifford Ray Rowe Jr.

Nancy Rozendal

Margaret Mary Mateer and John R. Pearson

Dr. John Brian O’Donnell

Dr. Martin Rothberg

Candace R. and Gerald W. Rowe

Janet Klein Potter and Robert H. Potter, M.D.

Martin A. Murcek, M.D.

Steven Barry Roth, M.D.

Susan Lynn Greenspan, M.D., and Neil M. Resnick, M.D.

Barbara B. Pearson

James F. O’Donnell Russell J. Munson, M.D.

Ronald M. Roth, M.D.

Barry Richard Reznick, M.D. C.H. William Ruhe II, M.D.

Edward Vincent Puccio, M.D.

Brian Thomas Rice, M.D.

Sally and Bryan Putt

Lisa Ann Tollini, M.D., and David Rice

Angelo S. Runco, M.D.

James H. Rice

Margaret S. and Robert G. Runnette

Marilyn Quatroche and Dr. Thomas J. Quatroche Sr.

Walter G. Rich

Ann Russell Trust

Joann Hawkins Queenan and C.J. Queenan Jr.

Deborah Ricottone and Dr. Anthony Ricottone

Deanna Love Rutman, M.D.

Evelyn Tabacek Quinn and John R. Quinn, M.D.

Sharon A. Riddler, M.D.

Abby and Reid Ruttenberg

Suzanne K. and William W. Reilly Sr.

Maureen and Dr. Richard J. Saab

Christian Riley

Dorothy N. Saladiak, Ph.D.

Mona and Robert W. Riordan

Joseph Salkowitz, D.M.D.

Linda and James Rumbaugh

Donald H. Quint, M.D. Mindy Goldstein Rabinowitz and Jay Steven Rabinowitz, M.D.

Noga and Devon Ruttenberg

Richard R. Ritter, M.D.

Marc Alan Saltzman, M.D.

Mr. and Mrs. Richard F. Rivers Jr.

Helen E. Salvin

Jonathan S. Raclin

Marc B. Robertshaw

E. Ronald Salvitti, M.D.

Dimitri M. Petro, M.D.

Jon M. Raetz

E. Annette Robertson, M.D., and John Joseph Robertson, M.D.

A. Neil Salyapongse, M.D.

Leslie Petrone and Dr. Joseph F.A. Petrone

David M. Rahauser, M.D.

Robert N. Peters Jennifer Hawke-Petit and William A. Petit Jr., M.D.

Paula Milner Rachelefsky and Marvin Alan Rachelefsky, M.D.

Ben Sampson

Margaret V. Ragni, M.D. Sylvia and Donald M. Robinson

Pablo Jose Sanchez, M.D. Susan G. and Joseph G. Robinson Jr.

Margaret D. Larkins-Pettigrew, M.D., and Chenits Pettigrew Jr., Ph.D.

Beth Rahko and Peter S. Rahko, M.D. Toni M. Robinson-Smith, M.D.

Philip J. Sandler, M.D. Odell Robinson III Nancy G. and Hugh D. Sansom

JoAnn V. Narduzzi, M.D.

Dr. Michael J. Painter

Stephanie and F. Fred Pezeshkan

Dorothy L. Raizman, Esq., and Richard E. Raizman, M.D.

Donna A. and Frank Navratil

Kathryn Ann Paladino, Ph.D., and Peter T. Paladino Jr., Esq.

William C. Pfischner Jr., M.D.

Mr. and Mrs. Kiran Rajasenan

Janet C. Rocco

Regis Philbin

Mitchell P. Rales

Nicole M. and Joseph Piccirilli

Mary Catherine and Robert Michael Rocks

Steven M. Rales

Linda P. and Kenneth R. Piercy Preeti and Ivan Pinto

Jothi Ramanathan and Dr. Rameshkumar Ramanathan

Doris H. Rodman

Marjorie Cohn Saul, M.D., and Scott Howard Saul, M.D.

John R. Pipski

Edward V. Randall Jr.

Susan S. Rodriguez

Mary Savaren

Beth Piraino, M.D., and Paul Martin Piraino

Dr. and Mrs. Peter B. Randolph

Paul L. Rogers, M.D.

Mary C. Raspanti

Sharon C. and James Edward Rohr

Juliette Wait, M.D., and Michael Alan Savin, M.D.

Sally and John Pirris

David Rath

Stefania Ferrarese Romoff and Jeffrey A. Romoff

Robert Stanford Sawin, M.D.

Megan R. Pitcairn Michael P. Pitek III

Diana Mrvos Rath and Frank Eugene Rath Jr.

Patricia Regan Rooney and Daniel M. Rooney

Mr. and Mrs. Kenneth G. Sawyer

Maria Pia Platia, M.D.

Lillian Spang Rath Lucy Balian Rorke, M.D.

Leonard Keith Plocki, M.D.

The Rattner Family

Carol Mosites Scalo and John F. Scalo

Shawn Garrett Pobiner, D.M.D.

James Irving Raymond, M.D.

Evans Rose Jr., Trustee, and Patricia Rose

Marion Weinman Schafer and Irwin A. Schafer, M.D.

Louis E. Polakoff

Alexa S. and Mark L. Recchi

Nathaniel Neal Joseph Peter Nedresky, M.D.

William E. Palin, M.D.

Roberta Needleman and Dr. Herbert L. Needleman

William Edwin Palin Jr., M.D.

Pamela Rae Neish, M.D.

Catherine M. and James D. Palmer

Martha Dixon Nelson, M.D. Guita and Shahriyar Neman Susan L. Nernberg Noel Marie Newell

Arnold D. Palmer

Richard J. Pan, M.D. John Stanley Solters, M.D., and Patrick Pangburn Mary Panitch and Howard Barry Panitch, M.D.

Theresa F. and David C. Nicholson Haranath Parepally Mr. and Mrs. Anthony Nicolazzo Paul M. Paris, M.D. Dr. Theresa L. Nimick and Thomas H. Nimick Jr.

Sang C. Park, M.D.

Jane Nishio

Leah M. Pasquerilla

Mary Sanzari and ‡ Alfred Sanzari Frank and Athena Sarris

David M. Roderick

Wanda K. Panosh, M.D. Mr. and Mrs. Clark Nicklas

Jose W. Santiago, M.D.

Harry E. Poling, M.D.

‡ before an individual’s name indicates the person is deceased

David Leonard Rosenfeld, M.D.

William Michael Sawko, M.D.

143

DONORS

Cynthia C. and Keith M. Schappert

DEVELOPMENT

Sharon Enos Sclabassi, Ph.D., and Robert J. Sclabassi, M.D., Ph.D.

Diana Kay Lemley, M.D., and Paul Larew Shay, M.D.

Catherine M. Schellinger

Lari Marie Scorza, M.D.

Barbara and Herbert S. Shear

Mikell and A. William Schenck III

Allan G. Scott, M.D.

John G. Sheedy, M.D.

Mr. and Mrs. Kenneth Schiebel

Evelyn Steranka Scott, M.D., and Craig H. Scott, M.D.

Gracia Sheptak and Peter E. Sheptak, M.D.

John Harvey Scott, M.D.

Bruce S. Sherman

Amy and Sean Sebastian

Gene Victor Sherman, M.D.

Johnette Seecof and Richard Mark Seecof, M.D.

M. Eugene Sherman, M.D.

David Harry Schaub, M.D.

Sandra Alpern Schimel, M.D. John T. Schindler, M.D. Matthew David Schneider Robert E. Schoen, M.D., M.P.H. Donna S. and Stephen C. Schoettmer

Susan A. Sherman, M.D.

Nina R. Schooler

Elizabeth Segel and David P. Segel, M.D.

Mr. and Mrs. George A. Schroth

Charles Seigel, M.D.

Clyde John Schultheis, M.D.

Steven H. Seitchik

Cynthia Maher Shestak and Kenneth C. Shestak, M.D.

Patricia M. Sherry and Michael McClain Sherry, M.D.

Daniel G. Schultz, M.D.

Stewart Sell, M.D.

Patricia A. and David R. Shields

Bonita D. Schultz and Edward D. Schultz, M.D.

Barbara A. Seltman and M. Alfred Seltman, D.M.D.

Josephine Ollu Shively and John G. Shively, M.D.

Maxine W. Schultz

Katharine H. Servick

Jacqueline Shogan and Jeffrey Edward Shogan, M.D.

Valerie D. Schultz and Robert Francis Schultz, Esq.

‡Estate of John J. Shagovac Joan D. Shanahan

Mr. and Mrs. Bruce Shriver

Joel Steven Schuman, M.D.

J. Michael Shane

Ivan A. Shulman, M.D.

Eileen Caulfield Schwab

Margaret N. and Robert L. Shannon

Carol J. Scicutella, D.O.

William Guy Sharra, M.D.

Robert Louis Sciulli, M.D.

C. Gibson and Velma B. Shaw Trust

Marion Sieber Anna L. and Mark S. Silberman David C. Sill, M.D. Alice Silverblatt Joseph S. Silverman, M.D. Elizabeth Swart Silvers and Stewart Alan Silvers, M.D.

Psychiatrist and pilot Sylvester

The Doctors S. Sutton Hamilton

Susan T. Silversmith

Sutton Hamilton III,

Maria Estela Simbra, M.D.

M.D., and Carol Hamilton with their 1947 Piper Cub

If something like an M.D./ Ph.D. program had been available when Sylvester Sutton Hamilton III started his medical education in 1957, he would have been first in line. A Pitt School of Medicine alumnus from the class of 1961, Dr. Hamilton is the former chair of psychiatry at the University Medical Center at Princeton and former director of the psychiatry residency program at the Hospital of the University of Pennsylvania. Although technically retired, he still maintains a private practice in Princeton. Dr. Hamilton, along with his wife, Carol; daughter, Julie; and son, S. Sutton IV, recently established the Drs. S. Sutton Hamilton Medical Scientist Training Program (MSTP) Scholar Award for Pitt M.D./ Ph.D. students. The scholarship is designed to support students who are interested in both the research and clinical aspects of medicine. Students are eligible for the award if they have completed their Ph.D. work and are two years away from their M.D. degree. The award covers the last two years of tuition and includes a $2,000 stipend for the duration of the scholarship.

The Hamiltons created the award in honor of their family’s four uninterrupted generations of physicians. Dr. Hamilton’s grandfather, the original S. Sutton Hamilton, maintained a practice in Punxsutawney; his father, S. Sutton Hamilton Jr., was an intern at Presbyterian and Magee Hospitals in the 1930s before returning to Punxsutawney to practice; and S. Sutton Hamilton IV received his medical degree from Pitt in 1997 and is now assistant director of the Family Medicine Residency Program at Underwood-Memorial Hospital in Woodbury, New Jersey. While the other S. Sutton Hamiltons focused on general medicine, Dr. S. Sutton Hamilton III chose to specialize in psychiatry. “I’ve always enjoyed the whole breadth of medicine,” he explains, “but I guess I’ve always figured the most interesting and exciting approach is to go straight to the top. It’s the brain that makes us human. It’s the control center.” He cites his service as a military internist on an Air Force base in Texas as one experience that brought home the fact that “lots of physical problems have psychological aspects, and vice versa.”

Dr. Hamilton says that what intrigued him most when he was in training were the exciting things happening in the field of neuroscience. “It was clear that people who were using technology like magnetic resonance imaging and even early versions of computers were on the brink of being able to produce models that would teach us a great deal about the brain, but they just weren’t quite there yet.” The family hopes its gift will serve as an incentive for medical students who are interested in furthering their research education but are concerned about a lack of resources or the accrual of student loan debt. By focusing their support on the education of a clinician / scientist, the Hamiltons believe the scholarship will benefit not only the student but also the other physicians, researchers, and patients with whom he or she comes in contact. “I believe in the power of leverage,” says Dr. Hamilton, “and in the ability of a well-placed person.”

Mr. and Mrs. Kevin D. Simmons Rosa Lynn Pinkus, Ph.D., and Richard L. Simmons, M.D. Virginia C. and Richard P. Simmons Jaclyn R. and Brian C. Simon Karen Shakoske and Henry Simonds Juliet Hillman Simonds Retta and Elliott Singer Gurmukh Singh, M.D., Ph.D. April Troutman Sipos Lawrence Joseph Sipos, Esq. Richard V. Skibbens, M.D. William Dennis Slemenda, M.D. Jewel M. Slepchuk Carrie Slivka and Adam Slivka, M.D., Ph.D. Charles R. Sloan, M.D. Carol Ann Slomski, M.D. Robert Nathan Slotnick, M.D., Ph.D. Mary and Joseph Smallwood

‡ before an individual’s name indicates the person is deceased

145

146

DONORS

Lawson Charles Smart, M.D.

Charles R. Stewart, M.D.

Bradley Thompson

John B. Vincent

Dorothy and John C. Weidman Jr.

Susan Berger Smerd, Ph.D., and Peter Smerd

Mary N. Stewart

Harry Addison Thompson II

Patricia M. and Ronald L. Violi

John E. Weigel Jr., M.D.

Marcia Stewart and Mervin S. Stewart, M.D.

Mark Ewing Thompson, M.D.

Molly E. and John P. Vitlar

Susan and Bruce B. Weiner

Robert Jorden Thompson, M.D.

Desa Simich Voelker

Susan Simon Weiner

Sara B. Thompson

Clifford R. Vogan, M.D.

The Weintraub Family

Todd Thompson, M.D.

Saralyn S. Vogel, M.D., and Victor G. Vogel, M.D.

Judith Weintraub

Beth Ann Bowman Smith, M.D., and Rev. Douglas C. Smith Earl Charles Smith, M.D.

Barbara Duffy Stewart and William H. Stewart Jr.

Florence K. Smith

Guy M. Stofman, M.D.

Beverly A. Smith and James A. Smith, M.D.

Nancy Stoller and Dr. Ronald G. Stoller

Jeanette and Jan D. Smith

H. Donald Stork

Lois T. Smith and Ross H. Smith Jr., M.D.

Jean C. and Charles J. Stout

Alice Snyder Frank Neal Snyder Jr. Mr. and Mrs. Lee F. Snyder Thelma Snyder, D.M.D.

James A. Strite Jr., M.D.

William I. Snyder

Diane C. Strollo, M.D., and Patrick J. Strollo, M.D.

Judith Soberman, M.D.

Mr. and Mrs. Neil E. Strosnider

Marcia J. Weiss

Charles Wood Jr.

Marilynn Weiss

Edward Boss Wood, Esq.

Suzanne P. and Richard L. Wagner

Evelyn L. Weissman, M.D., and Ira M. Weissman, M.D.

Enid Wood and Richard D. Wood, Ph.D

Sanford Frank Tolchin, M.D.

Susan J. Wagner

William C. Welch, M.D.

William A. Woods, M.D.

Mark Tomsho, M.D.

Cynthia S. and Ronald B. Wahl

Emma Jane Griffith Woolley, M.D.

Barbara Ellen Trachtenberg

Jennifer A. Wahlig and Dr. John B. Wahlig

Martina Wells and Alan H. Wells, M.D.

Susan Mitchell Dunmire, M.D., and Samuel Aaron Tisherman, M.D.

David Paul Trachtenberg, M.D. Richard T. Trackler, M.D. Dr. Michael Tranovich

Laurie A. Sobol

Barbara Hart Sturges Thomas J. Tredici, M.D.

Teri and R. Damian Soffer Martin D. Sokoll, M.D. Francis X. Solano Jr., M.D.

‡Estate of Rueben Stutch, M.D. Bret Jonathan Stutzman ‡Estate of Leroy F. Stutzman, Ph.D.

Nancy Story Somers, M.D.

Erin A. Sullivan, M.D.

Richard C. Sorce, M.D.

Nancy Nan-Szu Sun, M.D.

Deborah K. Felt Spaletto and Robert Spaletto

Elizabeth L. and John P. Surma Jr.

Jeffrey Wayne Spear, Esq. Elaine and Howard A. Specter Silvia and Alexander C. Speyer III Mr. and Mrs. Holly W. Sphar Jr. Anthony Spinola, M.D. Mary Jo and Frank M. Spinola Christine A. Spolar Stephen B. Spolar, Esq. Norma W. Sproull Diane Dalton Stajduhar and Karl Conrad Stajduhar, M.D.

Andrea S. Sussman Edward Patrick Swan Jr. Robert John Swansiger, M.D. Cindy L. and David P. Swanson Michael D. Swanson, M.D. Marcia H. and Perry R. Swanson

Adria D. and Jerry L. Starkey Herbert Stein, M.D. Sharon and Adam Steinfurth Elaine and James Steinfurth Richard A. Steinman, M.D., Ph.D. Keith Richard Stephenson, M.D. Leonard Aaron Stept, M.D. Michael A. Stevens, M.D. Carole A. Bailey and Andrew N. Stewart

Gloria R. Tressler and Charles Samuel Tressler, M.D.

Elizabeth R. Myers, Ph.D., and Evan Vosburgh, M.D. Donald P. Vrabec, M.D. Gertrude and Lawrence M. Wagner

Charles L. Wells, M.D.

Hallie M. Worsey and Dr. M. Jonathan Worsey

Matthew B. Waldman

Lynne Marie Welshons

Catherine Woynarowski

Maureen and John J. Waldron

Maria R. and Timothy Richard Wesley

Ralph T. Wright

Norma and Charles J. Walsh

Debi and Harold W. Wheeler III

William R. Wright

Daniel Bernard Walsh, M.D.

Joan Wheeler

Florence M. Rollwagen and Dr. Lyn J. Yaffe

Mr. and Mrs. Larry Walsh

Nancy E. Wheeler

Aleida and Frank A. Trisoline Jr.

Lisa J. and Peter J. Walsh

R. James White III, M.D., Ph.D.

Darrell J. Triulzi, M.D.

Sharon Ann and William D. Walston Jr.

Priscilla Ann and Joseph Whiteside

Mike Yannazio Melissa Jane Yanover, M.D. Priscilla Tsao, M.D. Clifford N. Tschetter, M.D.

Eleanor B. Carson-Walter, Ph.D., and Kevin A. Walter, M.D.

Eva C. Tuttle Marie Limetti Uchic

Jacqueline Walter and William James Walter, M.D.

Debra Anne Udicious

Naomi and Peter B. Waltman

Edward Udicious Michael Underhill

Dr. Marina V.N. Whitman and Dr. Robert F. Whitman

Joyce Wong Yee and Archie L. Yee, M.D. Kathleen R. and Jon C. Yergler

Dr. Alan L. Whitney Richard Ian Whyte, M.D.

Mary Weaver Yost and William G. Yost Jr., M.D.

Barbara L. Widdoes

Bryant Yunker

Elisabetta and Kurt Wiedenhaupt

Jeffrey Allan Yunkun, M.D.

Phillips Wiegand Sr.

Ross Dennis Zafonte, D.O.

Sally Wiggin

Charles Edward Zaleski Jr., M.D.

Wayne Charles Waltzer, M.D. W. Alan Ward, M.D.

Charles M. Swindler Jr., M.D.

University of Pittsburgh Dental Medicine Classes of ’07 and ’08

Anne Logan Washburn, M.D., and W. Kenneth Washburn Jr., M.D.

Mr. and Mrs. Thomas Wild

Michael G. Zamagias

Donald F. Switzler Sr.

Juliana J. Uram

Hiroshi Washio, M.D.

Josephine H. and S. Donald Wiley

Mr. and Mrs. Frank J. Zappala Jr.

Charles Henry Sykes, M.D.

James I. Urbach, M.D.

John J. Wilkinson, M.D.

Nancy and Richard A. Zappala

Diane and Regis J. Synan

Michelle E. Wilkinson, M.D.

Kenton James Zehr, M.D.

Pamela Jeanne Szeeley, M.D.

Sandra L. Mort Usher and Thomas James Usher

Mary Chester Morgan Wasko, M.D., and Jonathan Wasko Steven D. Wasserman

Charles Canaan Williams Jr., M.D.

Zella R. Zeigler, M.D.

Mr. and Mrs. Donald J. Szoszorek

Thomas Charles Valenza, M.D.

Charles B. Watkins

Janet Beebe Taber and George H. Taber

Family of Jean Van Guilder

Mr. and Mrs. W.S. Watkins

Floris S. and Lloyd Van Horn

Pamela and Markos Tambakeras Julia H. Tamkevicz

Elizabeth Pickering VanKirk and James K. VanKirk, M.D.

Rosemary McCrudden and Gray Watson

Edward Michael Tapper, M.D. Robert C. Tarter, M.D.

John A. Staley IV Christine Stanko

Patrick Wayne Wolfe, M.D. Leon Wong

John Hampton Tippins

Mr. and Mrs. Edward M. Stripay Jr.

Dr. Michael Demetrius Voloshin

Loreen and Ronald L. Witt Susan E. Weintraub Marion Weiss Weisband and Benjamin J. Weisband, M.D.

Virginia L. Thornburgh and the Honorable Richard L. Thornburgh

Carol A. Strausbaugh

Stephanie Strazinsky

Brenda H. Witham and Timothy F. Witham, M.D.

Thomas Witomski, M.D.

Robert Timins

Bonnie and Thomas W. Strauss

Patricia B. Wissinger and H. Andrew Wissinger, M.D.

‡Estate of John S. Witherspoon, M.D.

Mr. and Mrs. Donald O. Thomson

Stephen Helmle Smith, Ph.D.

DEVELOPMENT

‡Estate of Florence K. Williams Valerie Trott Williams and John P. Williams, M.D.

Ariel Zelichov Laila D. Ziady Carol and Frank Zimmerman

Michael L. Williams

Nancy C. Watson

Kathleen A. and Theodore J. Williams

Margaret Vogt and Paul Joseph Zinsky, M.D.

Elizabeth Rose Vates

Kristina and William E. Watts

Edward L. Williamson, M.D.

Mr. and Mrs. Alan Ziperstein

Molly Vates and Thomas S. Vates III, M.D.

Paul Eugene Wawrzynski II, M.D.

Jeffry John Williamson

Ruth A. Zittrain, Esq.

Evan Lewis Waxman

Barry Steven Tatar, M.D.

‡Zelda S.H. Wilmurt

Tinkham Veale II Ethel and Ronald H. Taub Stephanie M. and J. Mark Veenis

Ellen May Mandel, M.D., and Lawrence W.N. Weber, M.D.

Robert W. Taylor Jay Vetere John R. Vickers

Janet Wei and Lawrence Ming Wei, M.D.

Bronwyn Vincent

Peter J. Weidhorn

Walter Joseph Telesz, M.D. Ashley and David A. Tesone II Ann E. Thompson, M.D.

‡ before an individual’s name indicates the person is deceased

Donna and Stuart A. Zlotnik

H. Randolph Wilson Jr., M.D.

Walter R. Zoladz III

Michael R. Wilson, M.D.

Debra Rutstein Zussman, M.D.

Richard A. Wilson, M.D. Ann Polak Winkelstein

147

DONORS

Mildred Danch, 1953

Mildred Danch Mildred Danch may not be the only lady whose vehicle of choice is a bright red Corvette, but she’s likely the only one in Columbiana County, Ohio, where her family farm is located. “I love my car,” she says. “It’s fun, and it gives me a lot of independence.” Independence has always been a guiding principle in Ms. Danch’s life, as has helping others. So at a time when many women were discouraged from working outside the home, Millie, as she prefers to be called, forged not one but two fullfledged careers. She graduated from the Youngstown Hospital Association’s nursing

school as a registered nurse in 1952, then trained as a flight attendant as well. In 1953, she began her 50-plus-year career in the aviation industry with Capital Airlines and then continued with United Airlines after it purchased Capital in 1961. “When I was flying out of Chicago, we would bid our schedules by the month, and I would give my schedule to Holy Cross Hospital,” she recalls. “Sometimes I would take my uniform to the hospital; and after I helped deliver babies, I would dress there in my stewardess uniform and rush out to Midway Airport to take my flight out. Then I would come back to Midway on a return flight, dash to the hospital, don my scrubs, and deliver more babies. I just loved it.” After her father’s death brought her back to the area, Millie continued to fly out of Pittsburgh. When she was called to serve on overseas flights, she moved to San Francisco, where she still maintains a home and lives part-time. When recent orthopaedic problems threatened to diminish Millie’s trademark energy, she turned to Lawrence S. Crossett, M.D., and William F. Donaldson III, M.D., both faculty members in the Department of Orthopaedic Surgery at the School of Medicine. “I couldn’t have asked for better treatment, from beginning to end,” Millie says — high praise, indeed, from an accomplished nurse with a lifelong commitment to top-quality health care. To help ensure that fewer orthopaedic patients will suffer the loss of their independence in the future, Millie has made plans to bequeath a substantial portion of her personal assets to the School of Medicine, including part of the family farm where she grew up and still lives. Her gift will honor and support the research of Drs. Donaldson and Crossett and their successors. She also plans to provide personal support to other fundraising activities for research and clinical medicine and hopes to inspire others to give as well. “Any time that I can do, I will do,” she says. The orthopaedic surgeries have made her “100 percent pain-free,” Millie says. The main drawback? “They wouldn’t let me drive for a while afterwards. But I’m go-go-going again now.”

DEVELOPMENT

CORPORATE AND FOUNDATION DONORS

American Academy of Otolaryngic Allergy

American Parkinson Disease Association Inc.

84 Lumber Company

American Academy of Otolaryngology

American Pharmaceutical Partners Inc.

American Association for Cancer Research

American Psychiatric Institute for Research Education

American Association for Hand Surgery

American Psychological Association

Abbott Laboratories Abiomed Inc. Abraxis Oncology Academic Pathology Associates Academy for Healthcare Education Acell Incorporated Active Media Services Inc. Adams Capital Management Inc. Advisory Board on Autism and Related Disorders Inc.

American Association for Liver Diseases American Association of Neurosurgeons American Association of Plastic Surgeons American Brain Tumor Association

Aesculap

American Cancer Society Inc.

Aesthetic Surgery Education Research Foundation

American Coaster Company Inc.

AFGE Local 644 Charities AFLAC Agouron Pharmaceuticals Inc. The AGS Foundation for Health in Aging

American College of Cardiology American College of Emergency Physicians

American Society for Bariatric Surgery American Society for Cell Biology American Society for Dermatologic Surgery Incorporated American Society for Pharmaceutical and Experimental Therapy American Society for Therapeutic Radiology and Oncology American Society of Clinical Oncology American Society of Echocardiography

American College of Rheumatology Research

American Society of Hematology

American College of Surgeons

American Society of Highway Engineers

Alabama Power Company

American Diabetes Association

Alcoa Foundation

American Dietetic Association

Alcon Research Ltd.

American Eurocopter

American Society of Transplant Surgeons

All in Good Taste Productions Inc.

American Federation for Aging Research

American Society of Transplantation

American Society of Nephrology

Allegheny County Chapter of Thrivent Financial Lutherans Allergan Inc. Alliance for Lupus Research

American Textile Company American Foundation for AIDS Research

American Thoracic Society

American Foundation for Suicide Prevention

American Urological Association Foundation

American Foundation for Surgery of the Hand

Amgen Inc.

Alliance Imaging AllTel Direct Aloka Alpern Rosenthal & Company The Alpert Family Foundation Alpha-1 Foundation ALS Association, Western PA Chapter

American Foundation for Urologic Disease Inc. American Gastroenterology Association American Head and Neck Society American Headache Society

ALS Therapy Development Foundation

American Health Assistance Foundation

Alternatives for Research and Development Foundation

American Heart Association

Amyotrophic Lateral Sclerosis Association Anonymous Antigenics Inc. Aon Foundation Applied Medical Aqua Bears Aramark Corporation Architectural Network Inc.

Alzheimer’s Assistance and Referral Network Alzheimer’s Association Alzheimer’s Disease Cooperative Study

Ares Management II LP American Heart Association, Pennsylvania Affiliate

Arthritis Foundation

American Homecare Supply

ArthroCare

American Institute for Cancer Research

Arthurs Philanthropic Fund Association of American Medical Colleges

The AMDA Foundation Inc.

American Joint Committee on Cancer

American & Efird Inc.

American Liver Foundation

AstraZeneca Pharmaceuticals LP

American Academy of Child and Adolescent Psychiatry

American Lung Association

AtriCure

American Lung Association of Pennsylvania

Autism Society of America

American Academy of Hospice and Palliative Medicine

American Medical Association Foundation

Astellas Pharma US Incorporated

Autism Society of America, Greater Harrisburg Area Chapter

149

150

DONORS

DEVELOPMENT

AXA Foundation Inc.

Breg Inc.

Edwards Lifesciences

Fiserv SourceOne

Bristol-Myers Squibb

Centerpulse Spine-Tech Incorporated

Copeland Fund

Axcan Scandipharm Inc.

Cordis Corporation

Eisai Inc.

Fisher Scientific Company

BAA USA Inc.

Bristol-Myers Squibb Foundation Inc.

Centocor Inc.

The CORE Network LLC

Elekta Instruments Inc.

Babst, Calland, Clements and Zomnir PC

Eli and Edythe L. Broad Foundation

Cerner Corporation

Countrywide Financial

Eli Lilly and Company Foundation

The Audrey Hillman Fisher Foundation Inc.

Brooks Family Foundation

Cervical Spine Research Society

Coury Financial Group LP

Elite Runners and Walkers Inc.

Covance Inc.

Elliott Company

Deno F. Barsotti Family Fund

Philip V. and Anna S. Brown Foundation

Grant Channell Memorial Fund Charlesbank Capital Partners LLC

Creative Displays & Packaging Inc.

The Ellison Medical Foundation

Barton Malow Company

Ben F. Bryer Foundation

Chicago White Sox

Credit Suisse First Boston LLC

Ellwood Group Incorporated

Barudan America Inc.

Bryne Foundation

Creditors Interchange

Emergency Medicine Foundation

Baseball Office of the Commissioner

Buchanan Ingersoll & Rooney PC

Chick’s Sporting Goods and Ski Shop Inc.

S.M. Cristall Company Inc.

Bates Jackson Engraving Company

Buffalo Bills Alumni Foundation Inc.

Children’s Brittle Bone Foundation

Flight Attendant Medical Research Institute

Baxter Healthcare Corporation

Buffalo Sabres

Children’s Hospital of Pittsburgh of UPMC

Employees of Hamilton Buick Pontiac GMC and Hamilton Mazda

The Baxter International Foundation

Buffalo Sabres Foundation

Forest Pharmaceuticals Inc.

Baylor Health Care System

The Buncher Company

Michael Baker Corporation

Beaver Area Jaycees Beckwith Machinery Company

Buncher Family Foundation

The Beez Foundation Inc.

Burlington Northern Santa Fe Foundation

Bell Helicopter Textron

Burroughs Wellcome Fund

Bell Manufacturing Company

Burt, Hill

Bellefield Presbyterian Church

Buzztone.com Inc.

Berchtold Corporation

Campbell Foundation

Meyer & Merle Berger Family Foundation Inc.

Charles T. Campbell Charitable Foundation

Berlex Laboratories Inc.

Crohn’s & Colitis Foundation

The Lilah Hilliard Fisher Foundation Inc. The Matthew Hillman Fisher Foundation The Nina Baldwin Fisher Foundation Inc.

Florida Marlins LP

Crown Hotel Investments LP

The Children’s Leukemia Research Association, Inc.

CTR Holdings Inc.

Employees of Washington Mutual in Bethel Park

CTRC Research Foundation

Entertainment Industry Foundation

ChiRhoClin Incorporated

Cubist Pharmaceuticals Inc.

Enzon Pharmaceuticals

Chiron Corporation

Equitable Resources Foundation Inc.

Choice Marketing Company

Cumberland Valley Breast Care Alliance

Cine-Med Incorporated

Curbell

Ciphergen Biosystems Inc.

CV Therapeutics

Citigroup Global Markets Inc.

Cystic Fibrosis Foundation

CJ Systems Aviation Group

The Myrtle Forsha Memorial Trust Victor Forstmann Inc. Fort Pitt Capital Group Incorporated The Foster Charitable Trust ERBE USA Incorporated The Foster Family Foundation Ernst & Young Ernst & Young Foundation

Foundation for Anesthesia Education & Research

Esophageal Cancer Awareness Association Inc.

Foundation for Gene & Cell Therapy

Dana Foundation

Clarus Medical LLC

Danaher Foundation

The James Ewing Foundation Inc.

Foundation for Physical Medicine and Rehabilitation

Clayton Sleep Institute LLC

Dane Electric Company

R.W. Caldwell Associates Inc.

Evaheart Medical USA Inc.

Delaware North Companies Inc.

Evans National Bank

Michael J. Fox Foundation for Parkinson’s Research

Berry Petroleum Company

Canada Hair Cloth

The Cleveland Foundation

Deloitte & Touche LLP

Excela Health

Fox Sports Net Pittsburgh LLC

Cancer Foundation for Melanoma Research

Cleveland Indians Baseball Company

BGI Interiors

Cleyn & Tinker International Inc.

Deloitte Services LP

The Mike Exler Pancreatitis Benefit

Francis Family Foundation

Coalition for Pulmonary Fibrosis

Decker Denko Foundation

Expression Diagnostics Incorporated

Francis Foundation

Codman & Shurtleff Inc.

DePuy Mitek Inc.

ExxonMobil Foundation

Cohen & Grigsby PC

Dermatology Foundation

Eye & Ear Foundation

The Gerald J. and Dorothy R. Friedman New York Foundation for Medical Research

COIS Local Staff Development Task Force

DHJ Canada Incorporated

Fabric Czar USA Inc.

P.J. Dick Incorporated

Facility Merchandising Incorporated

Coit Services Inc.

Ditto

Fair Oaks Foundation Inc.

Frontier Science & Technology Research Foundation Inc.

Coldwell Banker Residential Brokerage Corporation

Diversified Premier Consultants LLC

Fairbanks-Horix Foundation

Fujinon Inc.

Dominion Foundation

The Falk Group LLC

Fujisawa Healthcare Inc.

Robert C. Douthitt Irrevocable Trust

Maurice Falk Fund

G & G International LLC

Dress Circle Inc.

Fannie Mae Foundation

Gardner Carton & Douglas LLP

DSF Charitable Foundation

Fayette Regional Health System

Blanche G. Garwood Trust

Duane Morris LLP

Federated Investors Foundation Inc.

Shawn Gaertner Foundation

Doris Duke Charitable Foundation

Federated Investors Inc.

Gateway Financial Group Inc.

Duquesne Light Company

Federation of Clinical Immunology Societies

GE Foundation

BHNT Architects PC Margaret J. Biddle Charitable Trust

Cancer Research and Prevention Foundation

Birmingham Foundation

Cancer Research Institute

big Burrito Restaurant Group Binational Science Foundation

Anna L. Caplan and Irene V. Caplan Endowment Fund

Biomet Manufacturing Corporation

CardiacAssist Inc.

Biosphere Medical Inc.

Cardinal Health Incorporated

Biotronics

Cardiovascular Institute

Bishop Metals Inc. Bison Baseball Inc. Bodymedia Inc. Boehringer Ingelheim Pharmaceuticals Boich Group Boland Sales Company Inc. Boncraft Incorporated Bond, Schoeneck & King PLLC

Carlow Campus School PTA Carlow University

College of American Pathologists Foundation

Carmel Partners Investment Fund

Collegiate Licensing Company

Carnegie Mellon University

Comcast

Caroselli Beachler McTiernan & Conboy

Common Plea Restaurant

Carr Textile Corporation

Community Care Behavioral Health Organization

Wendy Will Case Cancer Fund Inc.

Computer Associates International

CCF Agnes & Francis Cosgrove Memorial

Computer Enterprises Inc.

CCIM Institute

Nancy T. and William S. Conover II Fund

Boston Red Sox Foundation Boston Scientific Corporation Bozzone Family Foundation Brashear LP

CDM Celgene Corporation

Easley & Rivers Inc. Eastman Machine Company

Ferry Electric Company

Construction General Laborers & Material Handlers

Eat’n Park Hospitality Group Inc.

Fifth Third Bank

Eaton Charitable Fund

Finish Line

Cook Biotech Incorporated

Eaton Office Supply Company Inc.

Cook Incorporated

First Commonwealth Financial Corporation

EBI Medical Systems Inc.

Cookie Cravings Inc.

Eckert Seamans Cherin & Mellott LLC

Celltech Pharmaceuticals Inc. Center for Eating Disorders PA Center for Emergency Medicine of Western Pennsylvania

Eagle Buckram Company Inc.

FEDEX Trade Networks The Herbert G. Feldman Charitable Foundation

Congress of Neurological Surgeons

Bontex Borderline Personality Disorder Research

Dystonia Medical Research Foundation

Friends in Alice Springs

The GEMI Fund Genentech Inc. General Motors Cancer Research Foundation Genesco Genomic Health Incorporated Genzyme Corporation Geo-Mechanics Inc. Gerald Auto Group

FISA Foundation The Giant Eagle Foundation

151

152

DONORS

Giant Eagle Incorporated Gilead Sciences Incorporated

Teresa & H. John Heinz III Charitable Fund

DEVELOPMENT

Intel Corporation

KPMG Peat Marwick LLP

Interim Healthcare

The Krog Corporation

March of Dimes Birth Defects Foundation

Intermodal Air Inc.

L.J. Aviation

Marcus & Shapira LLP

Intermune Incorporated

Ladies Auxiliary Department of Pennsylvania

The Nancy Lurie Marks Family Foundation

Ladies Hospital Aid Society of Western Pennsylvania

The Marsh Family Foundation Marsh & McLennan Companies Inc.

Millennium Pharmaceuticals Incorporated

Asmund S. Laerdal Foundation Inc.

Marsh USA Inc.

Mine Safety Appliances Company

Lake Shore Properties Inc.

Marshall Elevator Company

Mitsubishi Electric Corporation

Microsoft Corporation Milhelm Foundation for Cancer Research

Merle E. and Olive Lee Gilliand Foundation

Vira I. Heinz Endowment

Gist Cancer Research Fund

International AIDS Vaccine Initiative

GlaxoSmithKline

Gertrude E. Hellerman Charitable Trust Fund

GlaxoSmithKline Foundation

Henderson Brothers Inc.

International Brain Research Organization

Global Environmental Management Initiative

Hergenroeder Rega and Sommer LLC Heritage Management Services Inc.

International Brotherhood of Electrical Workers

Global One Headwear

High Q Foundation

International Myeloma Foundation

Larrimor’s

The Martin Group LLC

Modell’s Inc.

GOG Tissue Bank

Highmark Incorporated

Joseph E. Lavine Foundation

The Donald D. Mateer Foundation

Goldberg Persky Jennings & White PC

Highmark Foundation

International Transplant Nurses Society

Lawley Agency Insurance

Matthews, Bartlett & Dedecker Inc.

Morby Family Charitable Foundation Inc.

Hilb, Rogal & Hamilton Company

Interpublic Group

Lawley Service Insurance

The Hillman Company

H. Lazar & Son Inc.

Jas H. Matthews & Company Educational and Charitable Trust

Morgan Stanley

Intestinal Disease Foundation

The Hillman Foundation Inc.

IP Logic

The Mario Lemieux Foundation

James S. McDonnell Foundation

Lendable Linens

McGettigan Partners

Mountaineer Race Track & Gaming Resort

The Henry L. Hillman Foundation

S.W. Jack Drilling Company

The Henry Lea Hillman Jr. Foundation

Jacobs Vehicle Systems

Leukemia & Lymphoma Society

Jaeckle Fleischmann & Mugel LLP

William G. McGowan Charitable Fund Inc.

Leukemia Research Foundation

Golfers vs. Cancer Classic Goodlette, Coleman & Johnson PA Goodrich Foundation W.L. Gore & Associates Gott Family Foundation

Heinz World Headquarters

Michael Milken Foundation Millcraft Industries Incorporated

J.P. Morgan Chase & Company

MPC Corporation

McGuire Woods LLP

Multiple Myeloma Research Foundation

McKesson Corporation

Murrysville-Export Rotary Club

GPS Construction Services LLC

Juliet Ashby Hillman Foundation

James Services

Levitronix LLC

Grable Foundation

Summer Lea Hillman Foundation

Janssen Pharmaceutica Products LP

Lexus of North Hills

The William Talbott Hillman Foundation Inc.

Japan-North America Medical Exchange Foundation

Lia Agency Inc.

McKinsey and Company Incorporated

Muscular Dystrophy Association Inc.

Grant Oliver Corporation

L.I.S.Z. Foundation Inc.

McKnight Endowment Fund

Mylan Laboratories Inc.

Lloyd Foundation

N.S.A.B.P. Foundation Inc.

Harry J. Lloyd Charitable Trust

McMahon & Cardillo Communication Inc.

The Mary Hillman Jennings Foundation

Louis Anthony Jewelers

MDS Nordion

Jerome Medical

Love Family Foundation

MedImmune Inc.

Jewish Healthcare Foundation of Pittsburgh

Walt and Sonya Love Cancer and Lupus Foundation

Medisys Health Communications LLC

National Alliance for Autism Research Inc.

Medrad Incorporated

National Brain Tumor Foundation

The Luminescence Foundation Inc.

Medtronic Inc.

Lupus Foundation of America

Mellam Family Foundation

National Childhood Cancer Foundation

William T. Grant Foundation Greenwall Foundation

The Hinchman Foundation

Grubb & Ellis Company

Hire Demand LLC

Guidant Guidant Foundation Incorporated

The Orris C. Hirtzel and Beatrice Dewey Hirtzel Memorial Foundation

J.J. Gumberg Company

Hockey Western New York LLC

JDK Design Jennings Local School District

Muse Foundation

Nabtesco Corporation NARSAD Research Institute Inc.

Gunderson Incorporated

Emma Clyde Hodge Memorial Fund

Gunold USA Incorporated

Holiday Valley

H & K Publications Inc.

Horizon Medical Products Inc.

Joan’s Legacy: The Joan Scarangello Foundation

Robert Half International Inc.

Hospira Inc.

Jobs Weekly Inc.

M & T Bank

Mellon Bank NA

National City Bank of PA

The Eden Hall Foundation

Hospital and Healthsystem Association

Johnson & Johnson

The M & T Charitable Foundation

Mellon Financial Corporation

National Council of Jewish Women

Henry E. Haller Jr. Foundation

M & T Insurance Agency Inc.

Mellon Financial Corporation Foundation

National Emblem Incorporated

John Hancock Financial Services Inc.

Houston Harbaugh PC

The Robert Wood Johnson Foundation

Hand & UpperEx Center

The Howard Hughes Medical Institute

Michael Joseph Development Corporation

R.K. Mellon Family Foundation

National Hemophilia Foundation

MacroPore Biosurgery Inc.

Richard King Mellon Foundation

National Hockey League Foundation

Human Frontier Science Program Organization

Juvenile Diabetes Foundation Madsen, Sapp, Mena, Rodriguez & Company PA

Members of the Steel City League

National Kidney Foundation

Memorial Healthcare System Mercer Human Resource Consulting

National Kidney Foundation of Western Pennsylvania

Merck & Company Inc.

National Multiple Sclerosis Society

The Merck Company Foundation

National Neurofibromatosis Foundation Inc.

Jonathan M. Harris Foundation Morris H. and Gertrude M. Harris Foundation

HVL Incorporated

KDKA-TV/WNPA-TV Kelly-Rielly-Nell Associates Inc.

The Richard N. Harris Fund

The John D. and Catherine T. MacArthur Foundation

Magee-Womens Hospital of UPMC

iBalance Medical Inc.

Kennametal Foundation

Magee-Womens Research Institute

IBEW Local Union No. 5

Kirpatrick & Lockhart Preston Gates Ellis LLP

Major League Baseball

The John A. Hartford Foundation Hat World Inc. IBM Corporation The Hawksglen Foundation IBM Employee Services Center Headstart Licensed Products LLC

Malady and Wooten Public Affairs LLP

Merrill Lynch & Company Inc. Merrill Lynch & Company Foundation Inc.

National Ovarian Cancer Coalition

Klett Rooney Lieber and Schorling

Malignant Hyperthermia Association of the United States

Metanexus Institute

National Pancreas Foundation

Edward Mallinckrodt Jr. Foundation

The Lenore and Howard Klein Foundation Inc.

IBM International Foundation HealthNow New York Inc. IKM Incorporated Heart Failure Society of America Inc.

National Headache Foundation

National Neurotrauma Society

IKON Office Solutions Immunetrics Incorporated

Knoll Inc.

Management Engineering Corporation

Metropolitan Life Foundation

National Parkinson Foundation

Heart, Lung, and Esophageal Surgery Institute

The Klingenstein Third Generation Foundation

Meyer & Eckenrode Insurance Group

National Sleep Foundation

Heartland Homes Inc.

The Impact Group

Knorr-Bremse AG Group

Managers Investment Group LLC

Incyte Corporation

Marathon Oil Corporation

Howard Heinz Endowment

Independent Health Association Inc.

Susan G. Komen Breast Cancer Foundation

The Robert Bensen Meyer Jr. Foundation Inc.

NBA Properties Inc.

Hefren-Tillotson Inc.

MGI Pharma Inc.

Integrated Therapeutics Corporation

The Curtis I. Kossman Foundation

Nemacolin Woodlands Resort and Spa

Michigan Instruments Incorporated

NCME Holding Corporation

153

154

DONORS

Neurologic and Orthopedic Institute of Chicago Neuropsychiatric Research Institute Neuroscience Technologies Inc. Neurosciences Education and Research Foundation Neurosurgery Research and Education Foundation

DEVELOPMENT

Oxford Development Company

Phoenix Marketing Solutions LLC

R & B Medical Inc./Arthrex Inc.

Saint Baldrick’s Foundation

Smith Barney

P & W Foreign Car Services Inc.

The Picower Foundation

Radelet McCarthy Architects

Salix Pharmaceuticals Inc.

P.R. Pharmaceuticals Incorporated

Pietragallo Bosick & Gordon LLP

The Randolph Foundation

Smurfit-Stone Container Enterprises Inc.

P4 LLC

Pittsburgh Associates

Rauch Foundation

Myles D. and J. Faye Sampson Family Foundation

Snee-Reinhardt Charitable Foundation

Pittsburgh Athletic Association

Reed Smith LLP

San Diego Padres LP

The Paget Foundation

John Nesbit & Sarah Henne Rees Charitable Foundation

Sands Capital Management Inc.

S.R. Snodgrass AC

Pittsburgh Emergency Medicine Foundation

Sangstat

G. Whitney Snyder Charitable Fund

Michael J. Parada Walkathon

The Pittsburgh Foundation

Regeneration Foundation

Sanofi Pasteur

Society for Academic Emergency Medicine

Pacific Vascular Research Foundation

New Balance Foundation Paradiso Group

Pittsburgh Hospitality House

Thomas M. Reich & Associates

Sanofi-Synthelabo Inc.

New Enterprise Stone and Lime Company Inc.

Elsa U. Pardee Foundation

Pittsburgh Life Sciences Greenhouse

Relco Inc.

Saperston Asset Management Inc.

New Era Cap Company Inc.

Parker/Hunter Incorporated

Pittsburgh Mennonite Church

Reliant Pharmaceuticals Inc.

Scaife Family Foundation

New York Academy of Medicine

The Parkinson Alliance Inc.

Pittsburgh Opera

The Relizon Company

Schering Plough Research Institute

Society of American Gastrointestinal Endoscopic Surgeons

The New York Mets Foundation Inc.

Parkinson Chapter of Greater Pittsburgh

Pittsburgh Penguins

Emelie Renziehausen Trust

Schering Sales Corporation

Society of General Internal Medicine

Pittsburgh Pirates

Research to Prevent Blindness

Society of Teachers of Family Medicine Foundation

Pittsburgh Steelers Sports Inc.

The Research Foundation for Mental Hygiene Inc.

Schnader Harrison Segal and Lewis LLP School of Medicine, Department of Anesthesiology

Society of University Surgeons

New York Yankees Parkinson’s Disease Foundation New York Yankees Foundation NewBold Inc. NFL Charities NHL Foundation NMT Medical Inc. Nordic Fisheries Normandy Industries North American Spine Society North Hills Senior High

Parsons Brinckerhoff Group Administration Inc. Partners Healthcare Systems

The Platt Family Foundation

Rett Syndrome Research Foundation

Plextronics Inc.

RheoGene

School of Medicine, Department of Pathology

Sony Electronics Inc.

Pathology Oncology Informatics Team

PNC Bank

The Rhode Island Foundation

The School of Sleep Medicine Inc.

Speed Motor Express of W.N.Y. Inc.

The PNC Financial Services Group

Ride For Life

Schwarz Pharma

Speed Transportation

PNC Foundation

Ride for Research

The Scienomics Group

Point Biomedical Corporation

Riggs Industries Inc.

Scientific-Atlanta Inc.

Alexander C. and Tillie S. Speyer Foundation

Polakoff Sports Sales Inc.

Riley, Hewitt and Sweitzer PC

Scios Inc.

Spinal Cord Research Foundation

Polk Foundation

Roadside Products

Scleroderma Foundation

St. Jude Medical Foundation

James C. Pontious and Margaret W. Pontious Foundation

Alex and Leona Robinson Family Foundation

Scleroderma Foundation of Greater Chicago

St. Louis Cardinals Ch. Shop Inc.

The Adrienne and Milton Porter Charitable Foundation

The Donald & Sylvia Robinson Family Foundation

Seattle Mariners Baseball Club

Theodore and Vada Stanley Foundation

Serono Inc.

Staunton Farm Foundation

Larry Potter Memorial Fund

Robroy Industries Shadyside Hospital Foundation

Steel City Boogie Club

Howard A. Power Scholarship Trust Fund

Roche Diagnostics Corporation

Pentax Precision Instrument Corporation

Shapiro Capital Management Company Inc.

Steel City Spine

Roche Laboratories Inc.

Praxair Inc.

Sherman Family Foundation

Margaret L. Stevens Foundation

Pepsi Bottling Group Inc.

Heinz C. Prechter Bipolar Research Fund

Roche Organ Transplantation Foundation

T.D. Patrinos Painting & Contractors PBS&J

Pediatric Brain Tumor Foundation

Novactyl Inc.

The Peirce Family Foundation Inc.

Novartis Pharmaceuticals Corporation

Penelec Erie Engineering Department

Novartis US Foundation

Penn Hills Police Department Pennsylvania Lions Hearing Research Foundation Pennsylvania / West Virginia Geriatrics Society

NVR Building Products Ogletree, Deakins, Nash, Smoak & Stewart PC

Solenture Inc.

PATA Charitable Foundation

NOVA Chemicals Inc.

Nuveen Investments

Society of Uroradiology

School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences

Partners in Change Inc.

Peak Vista Family Dentistry PC

NRG Energy Center Pittsburgh LLC

Respironics Sleep and Respiratory Research Foundation

Plastic Surgery Educational Foundation

North Side Foods

Novo Nordisk Inc.

Pittsburgh Tissue Engineering Initiative

Society for Progressive Supranuclear Palsy

Oil Service Inc. Pepsi-Cola Company R.C. Olson Enterprises Inc. Perfectly Natural Solutions Inc. Olympus Surgical and Industrial America Inc.

The Performance Group LLC

Oncology Hematology Associates

Personality Disorder Research Corporation

Open Society Institute

Respironics Incorporated

Dylan Todd Simonds Foundation Inc.

Lauri Strauss Leukemia Foundation

William H. Prentice Incorporated

Henry John Simonds Foundation Inc.

Stryker Biotech

Price Foundation

Romoff, Newman, Cesark & Daraio LLC Susan and Elihu Rose Foundation

The Juliet Lea Hillman Simonds Foundation Inc.

Stryker Endoscopy

PricewaterhouseCoopers LLP Princeton Insurance Company

RP Sales Inc.

The Procter & Gamble Fund

Orthopedic Research & Educational Foundation

Phi Rho Sigma Medical Society Endowment Fund

Osteogenesis Imperfecta Foundation

The Phillies

Ovarian Cancer Research Fund Incorporated

Phillips Lytle LLP

Procter & Gamble Pharmaceuticals Professional Baseball Promotion Corporation Prostate Cancer Foundation Protein Design Labs Inc. The Prudential Foundation J.P. Phillips Inc. Quaker Capital Management T.W. Phillips Gas & Oil Company

William E. Simon Foundation Inc.

Strategic Implications International LLC

Roesch Family Foundation

Pharmasset Inc. Pharmion Corporation

Stork Foundation

A.J. Silberman & Company Henry Clay Frick Rodgers Trust

Proceq USA Inc.

Orthopedic Associates of Pittsburgh Inc.

Sigma-Tau Pharmaceuticals Inc.

PremCom Corporation

Sunrise Medical Inc.

Talbott Lea Simonds Foundation Inc.

Surgical Infection Society

Simpson & McCrady LLC

RSM McGladrey Incorporated

Pharmacia & Upjohn Company Ortho-McNeil Pharmaceutical

Stellar Solutions Foundation

Precision Therapeutics

Pfizer Inc. Ortho Biotech Products LP

Charles F. Spang Foundation

Rockwood Manufacturing Company

The Pfizer Foundation Inc. Organ Recovery Systems

Solvay Pharmaceuticals Inc.

RSNA Research and Education Foundation

Simpson Family Foundation

Susquehanna International Group LLP

D.G. Sisterson & Company

Synerg IT Incorporated

Rugby Realty Company Inc.

Sky Insurance

Synthes USA

The Russo Family Charitable Trust Foundation Inc.

The Alfred P. Sloan Foundation

Sysco Food Services of Pittsburgh

S & T Charitable Foundation

Smith & Nephew Inc.

Systems Management Planning Inc.

SAB WABCO Group AB

Smith & Nephew Wound Management

Takeda Pharmaceuticals North America Inc.

SAI Consulting Engineers

155

156

157

Tamco Targe Energy LLC Teijin Pharma Limited Teine Keijinkai Hospital Teleflex-CT Devices Inc. Telik Inc.

Unither Pharmaceuticals Incorporated

Workflow One

University of Pittsburgh

World Heart Corporation

School of Medicine

University of Pittsburgh Physicians / Department of Obstetrics, Gynecology, and Reproductive Sciences

Wyeth

University of Pittsburgh Medical Center

Xanthus Life Sciences Incorporated

Teva Neuroscience Inc.

Wyatt Incorporated D E PA R T M E N T S

Wyeth-Ayerst Pharmaceuticals

158

Anesthesiology

160

Biomedical Informatics

Yates-Fund for Cancer Hope Unocal Foundation

Tex’s Auto Sales

Tim Yochim Memorial Tournament UPMC Health Plan

THANC Foundation UPMC Home Medical Equipment

Bryant & Nancy Yunker Foundation Incorporated

UPMC Presbyterian Medical Staff

William & Sylvia Zale Foundation

Therakos The Thoracic Surgery Foundation for Research and Education

Utility Workers Union of America

Thoratec Corporation

The V Foundation for Cancer Research

Three Rivers Aluminum Company Valeant Pharmaceuticals NA

162

Cell Biology and Physiology

164

Computational Biology

165

Critical Care Medicine

167

Dermatology

Zambelli Fireworks Manufacturing Company

168

Emergency Medicine

Carl Zeiss Meditech Inc.

170

Family Medicine

171

Immunology

173

Medicine

Three Rivers Orthopedic and Spine Products Inc.

Van Der Moolen Specialists USA LLC

Zenith Supply Company Incorporated

Tibotec Therapeutics

Van Dyk Business Systems

Zenner & Ritter Inc.

TimBar Packaging & Display

Ventana Medical Systems Inc.

Zimmer Spine

The Tippins Foundation

Veritable LP

Zimmer Incorporated

TissueGene Incorporated

Vestar Capital Partners

Zimmer-Randall Associates Inc.

TissueLink Medical Incorporated

Veterans Research Foundation of Pittsburgh

ZLB Behring LLC

VIACOM Television Stations

Every effort has been made to ensure the accuracy of these records. Any errors or omissions may be brought to the attention of the University of Pittsburgh and UPMC Medical and Health Sciences Foundation: 412-647-8462 or [email protected].

182

Molecular Genetics and Biochemistry

184

Neurobiology

186

Neurological Surgery

188

Neurology

190

Obstetrics, Gynecology,

193

Ophthalmology

195

Orthopaedic Surgery

197

Otolaryngology

199

Pathology

204

Pediatrics

Wachovia Foundation

210

Pharmacology

Wal-Mart Foundation

213

The Edith L. Trees Charitable Trust Trees Foundation Victory Cap Front Mfg. Company Inc. Trimeris Inc. Ethel Vincent Charitable Trust Triological Society Virco BVBA Trumbull Corporation Vircolab Inc. PMB 94 Try-It Distributing Company Inc. Virgil Nipper Group TTX Company

and Reproductive Sciences

Voyager Jet Center LLC Tube City LLC WABCO TWM Foundation U.S. Pallet Company UB Foundation Activities Inc.

Physical Medicine and Rehabilitation

Walnut Capital Management UCB Inc. Walnut Grove Assembly of God

214

Psychiatry

Walnut Neville Commons LP United Jewish Federation of Greater Pittsburgh

218

Radiation Oncology

Walt Disney World Dolphin

219

Radiology

United Mitochondrial Disease Foundation

The Raymond John Wean Foundation

223

Structural Biology

Weck Closure Systems

224

Surgery

United Parcel Service

229

Urology

United Business Systems Inc.

United Spinal Association

Roberta Weissburg Leathers

United States Gypsum Company

WellPoint Blue Cross of California

United States Steel Corporation

Wellpoint Foundation

The faculty lists were provided by

United States Surgical

West Herr Automotive Group Inc.

the Office of Faculty Affairs and

United Way

Wheeler Brothers Incorporated

were current as of July 25, 2007.

United Way of Allegheny County

The Whitaker Foundation

United Way of Central Maryland

The Nick Eric Wichman Foundation

United Ways of New England

Phillip H. and Betty L. Wimmer Family Foundation

The United Way of Washington County

Samuel & Emma Winters Foundation

The “visiting” prefix on faculty ranks is a temporary designation typically applied to new faculty members, usually for no more than one academic year, while their appointments are

Wilson-Cook Medical

being finalized.

158

A N E ST H E S I O LO GY

ANESTHESIOLOGY

John P. Williams, M.D., Dr. Peter and Eva Safar Professor of Anesthesiology and Critical Care Medicine and Chair

DEPARTMENT PROFILE

The Department of Anesthesiology provides excellence in perioperative medical care and pain management through active clinical practice, education, and research. A full spectrum of clinical anesthesiology services, from pediatrics and women’s health to care of trauma patients and veterans, is offered through 137 patient care sites at seven medical centers in western Pennsylvania. Other services include specialty pain care for orthopaedic surgery patients. The department has always been a leader in research, from Dr. Peter Safar’s groundbreaking work in the 1950s on resuscitation to the current focus on anesthetic mechanisms, pain, and patient safety.

Residency and Fellowship Training

Selected Research Highlights

Anesthesiology residencies prepare young physicians to specialize in perioperative medicine and pain management. Each major area of surgery is fully represented, and all subspecialty rotations are intramural. The faculty provides expertise on the anesthetic problems and procedures specific to each patient population so that graduating residents are comfortable managing complex intensive medical care for some of the most challenging and acutely ill patients. The department offers accredited fellowships in pediatric anesthesiology, pain medicine anesthesiology, and anesthesiology in critical care medicine. Additional fellowships are offered in cardiac, neuro, hepatic, regional, and obstetric anesthesiology.

Using a reproducible model of cardiac arrest and resuscitation in rats, Yan Xu, Ph.D., and colleagues have examined potential therapeutic effects of Oct-4(+) rat umbilical cord matrix (RUCM) cells in treating cerebral global ischemia. The researchers pretreated animals with Oct-4(+) RUCM cells by injection into the brain’s left thalamic nucleus, hippocampus, corpus callosum, and cortex. Histological analysis of the hippocampal CA1 region one week after cardiac arrest revealed that pretreatment with Oct-4(+) RUCM cells significantly reduced neuronal loss. Xu and colleagues also observed that the transplanted cells survived but had migrated significantly, with very few found directly in CA1. Therefore, the researchers concluded that the Oct-4(+) RUCM cells may repair tissue damage through an extracellular signaling mechanism, a finding that shows promise for the treatment of cerebral global ischemia. Li Meng, M.D., M.P.H., and Joseph J. Quinlan, M.D., have observed that after retromastoid craniectomy with microvascular decompression (MVD) of cranial nerves, patients frequently experience postoperative nausea and vomiting (PONV). In addition to patient discomfort, PONV can produce dehydration, electrolyte imbalance, and pulmonary aspiration; furthermore, the physical act of vomiting may increase intracranial pressure. Therefore, the researchers wanted to examine risk factors associated with PONV to enable physicians to target

high-risk patients. Meng and Quinlan found that despite the use of intraoperative prophylactic ondansetron in 99 percent of patients, the overall incidence of PONV was 60 percent during the first 24 postoperative hours. PONV incidence was highest for patients with MVD of cranial nerve V, and both female sex and use of the anesthetic desflurane were independent predictors of PONV. The researchers noted that administration of a prophylactic transdermal scopolamine patch before surgery resulted in significantly less PONV. Based on these results, Meng and Quinlan recommend that a combination of antiemetics be administered in advance to decrease the incidence of PONV after retromastoid craniectomy. Patients with visceral pain often experience pain referral to distant sites due to the viscerosomatic convergence of neurons at the spinal cord. Gerald F. Gebhart, Ph.D., and colleagues have examined whether hypersensitivity in referral sites is triggered by inflammation or by transient overexpression of nerve growth factor (NGF). The researchers found that inducing bladder inflammation increased NGF levels in bladder walls and significantly increased the response sensitivity to mechanical or thermal stimulation in the hindpaw of a rat. Gebhart and colleagues then injected a viral vector expressing NGF into the bladder to determine whether increased NGF levels, without direct inflammation, would produce a similar effect. The researchers again found that hindpaw mechanical and thermal stimulation was sensitized following NGF overexpression in the bladder. Based on these results, Gebhart and colleagues concluded that sensory pathway sensitization by inflammation or NGF contributes to the development of hypersensitivity in cutaneous referral sites, providing a potential explanation of the mechanism underlying the coexistence of pain syndromes in patients with functional diseases.

Centers Molecular Epidemiology and Pain Program Mitchell B. Max, M.D. Director Pittsburgh Center for Pain Research Gerald F. Gebhart, Ph.D. Director Peter M. Winter Institute for Simulation Education and Research (WISER) Paul E. Phrampus, M.D. (Department of Emergency Medicine) Director

Regular Faculty Endowed Chair John P. Williams, M.D. Dr. Peter and Eva Safar Professor of Anesthesiology and Critical Care Medicine and Chair Professors Barbara W. Brandom, M.D. Charles W. Buffington, M.D. Jacques F. Chelly, M.D., Ph.D. Doris K. Cope, M.D. Peter J. Davis, M.D. Gerald F. Gebhart, Ph.D. Joseph J. Quinlan, M.D. Yan Xu, Ph.D. Visiting Professors Mitchell B. Max, M.D. Jerome Parness, M.D. Margaret Mary Tarpey, M.D. Associate Professors Shushma Aggarwal, M.B.B.S. Nicholas G. Bircher, M.D. Richard J. Bjerke, M.D. Lawrence M. Borland, M.D. Charles D. Boucek, M.D. Ferenc E. Gyulai, M.D. Gregg E. Homanics, Ph.D. Mark E. Hudson, M.D. Bupesh Kaul, M.D. Michael Kentor, M.D. Robert G. Krohner, D.O. Gordon L. Mandell, M.D. Michael P. Mangione, M.D. Dawn A. Marcus, M.D. David G. Metro Jr., M.D.

Steven L. Orebaugh, M.D. Rita M. Patel, M.D. Raymond M. Planinsic, M.D. Nashaat N. Rizk, M.B.B.Ch. Erin A. Sullivan, M.D. Pei Tang, Ph.D. Susan W. Valeo, M.D. Manuel C. Vallejo, M.D., D.M.D. Helen R. Westman, M.D. Brian A. Williams, M.D. Visiting Associate Professors Paul Edward Bigeleisen, M.D. James Gordon Cain, M.D. Paul Kempen, M.D., Ph.D. Robert Clarence Stough, M.D. Jonathan H. Waters, M.D. Assistant Professors Miriam B. Anixter, M.D. Shawn T. Beaman, M.D. Cheryl Denise Bernstein, M.D. Arun Bhandari, M.D. Franklyn Paul Cladis, M.D. Patricia L. Dalby, M.D. Derek J. Davis, M.D. Catalin Silviu Ezaru, M.D. Patrick J. Forte, M.D. Theresa A. Gelzinis, M.D. Ibtesam A. Hilmi, M.D. William Roger Lariviere, Ph.D. Robert A. Lawler, M.D. Venkat R. Mantha, M.B.B.S. William R. McIvor, M.D. Li Meng, M.D., M.P.H. Andrew W. Murray, M.B.Ch.B. Todd M. Oravitz, M.D. Ryan C. Romeo, M.D. Carol E. Rose, M.D. Tetsuro Sakai, M.D. Shashank Saxena, M.B.B.S. Doreen E. Soliman, M.B.B.Ch. Joseph F. Talarico, D.O. Steven L. Whitehurst, M.D. Li-Ming Zhang, M.D. Visiting Assistant Professors Feng Dai, Ph.D. Tomas Drabek, M.D. Edmund Hilton Jooste, M.B.Ch.B. Elisabet Nystrom, M.D. Joseph Thomas Samosky, Ph.D. Charles Inshik Yang, M.D. Visiting Instructors Daniela Damian, M.D. Silviu Gligor, M.D. Research Instructors Xuehai Han, Ph.D. Eric Eugene Kelley, Ph.D.

DEPARTMENTS

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B I O M E D I C A L I N F O R M AT I C S

BIOMEDICAL

I N FO R M AT I C S

Michael J. Becich, M.D., Ph.D., Professor and Chair

DEPARTMENT PROFILE

The Department of Biomedical Informatics, the School of Medicine’s newest department, emerged from the Center for Biomedical Informatics. The department brings together a diverse group of faculty committed to improving biomedical research and clinical care through the application of innovative technologies. The new Center for Clinical and Translational Informatics, which uses biomedical informatics to maximize efficient information management and ensure data integration at each stage of clinical and translational research projects, is housed within the department. Faculty research explores areas like genomic and proteomic data mining, data warehouses and repositories, natural language processing, machine learning, intelligent tutoring systems and simulations, image analysis, grid computing, consumer health informatics, and biosurveillance.

Graduate Training

Selected Research Highlights

The Pittsburgh Biomedical Informatics Training Program prepares individuals for research and development careers emphasizing the application of modern technology to health care, basic biological and clinical research, and the education of health professionals. The program offers both master’s and doctoral degrees in biomedical informatics and includes a range of training experiences to accommodate the diverse backgrounds and aspirations of its students. Active participation in research and development projects is a key element of the training experience, and opportunities are available for both applied and theoretical research. If requested, specific concentrations of study can be obtained in the areas of bioinformatics, dental informatics, health services, and biosurveillance.

Advances in molecular biology and biomarker validation studies have generated a need for tissue banks to provide quality-controlled tissue samples with standardized clinical annotation. The National Cancer Institute’s Cooperative Prostate Cancer Tissue Resource (CPCTR) is a distributed tissue bank that comprises four academic centers and provides thousands of clinically annotated prostate cancer specimens to researchers. Michael J. Becich, M.D., Ph.D., and colleagues have helped to establish and evaluate CPCTR information management system architecture, common data element development, query interfaces, data curation, and quality control. Since its inception, CPCTR has made available several thousand cases of highly characterized prostate cancer biospecimens, including several tissue microarrays. Researchers working with CPCTR developed a Web site; and public, research, and member groups have used the Web tools for public querying of summary data on available cases, preparing requests and receiving tissues. The efforts of Becich and colleagues ensured that CPCTR can provide large volumes of carefully annotated prostate tissue for research initiatives and biomarker validation studies and can help to develop collaborative, large-scale, virtual tissue banks in other organ systems.

Rebecca S. Crowley, M.D., and colleagues have examined the effects of computer-based tutoring on diagnostic performance gains, metacognition, acceptance, and the diagnostic skills required for task performance in a medical training setting. The researchers designed two external problem representations: a case-focused representation, providing an open learning environment for students to freely explore evidence-hypothesis relationships within a case but not visualize the entire diagnostic space, and a knowledge-focused representation, providing an interactive representation of the entire diagnostic space but with more tightly constrained student actions. Metrics included results of pretest, post-test, and retention test for multiple choice and case diagnosis tests; ratios of performance to student-reported certainty; results of participant surveys; learning curves; and interaction behaviors during tutoring. Crowley and colleagues found that students showed significant learning gains after one tutoring session but observed no differences between the two interfaces in learning gains on post-test or retention test. However, only students in the knowledgefocused interface exhibited significant metacognitive gains from pretest to post-test and pretest to retention test. Student ratings were significantly higher for the knowledge-focused interface as well, indicating a higher metacognitive effect and user acceptance for the knowledge-focused external problem representation.

Electronic surveillance systems can be used to monitor triage chief complaints in hopes of detecting a disease outbreak sooner than with traditional reporting methods. Wendy W. Chapman, Ph.D., and Michael M. Wagner, M.D., Ph.D., have measured the accuracy of a Bayesian chief complaint classifier called CoCo, part of the Real-time Outbreak and Disease Surveillance (RODS) system developed previously by the researchers, as a first step in evaluating its utility in detecting outbreaks. The classifier assigns patients to one of seven syndromic categories (respiratory, botulinic, gastrointestinal, neurologic, rash, constitutional, or hemorrhagic) based on free-text triage chief complaints. The investigators compared CoCo’s classifications with criterion syndromic classification from the International Classification of Diseases, Ninth Revision discharge diagnoses. CoCo’s accuracy was tested on a set of 527,228 chief complaints from patients at a University of Pittsburgh Medical Center emergency department over a 13-year period. Approximately 16 percent of the patients were classified according to the criterion standard into one of the seven syndromes. CoCo’s classification performance (percent sensitivity, percent specificity) was as follows: respiratory (63.1, 94.3); botulinic (30.1, 99.3); gastrointestinal (69.0, 95.6); neurologic (67.6, 92.7); rash (46.8, 99.3); constitutional (45.8, 96.6); and hemorrhagic (75.2, 98.5). These results indicate that while CoCo’s specificity is high, sensitivity levels vary by syndromic classification, suggesting that further symptomatic system training in those conditions showing lower sensitivity (e.g., botulism) will improve CoCo’s overall accuracy in identifying relevant syndromic presentations.

Center Center for Clinical and Translational Informatics Michael J. Becich, M.D., Ph.D. Interim Director

Regular Faculty Professor Michael J. Becich, M.D., Ph.D. Associate Professors Gregory F. Cooper, M.D., Ph.D. Roger S. Day, Sc.D. Michael M. Wagner, M.D., Ph.D. Assistant Professors Brian E. Chapman, Ph.D. Wendy W. Chapman, Ph.D. Rebecca S. Crowley, M.D. Douglas B. Fridsma, M.D. Vanathi Gopalakrishnan, Ph.D. Dana Marie Grzybicki, M.D., Ph.D. William R. Hogan, M.D. Valerie Monaco, Ph.D. Garrick L. Wallstrom, Ph.D. Visiting Assistant Professor Shyam Visweswaran, M.B.B.S. Research Assistant Professor Fu-Chiang Tsui, Ph.D.

DEPARTMENTS

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C E L L B I O LO GY A N D P H YS I O LO GY

CELL

BIOLOGY

AND

PHYSIOLOGY

DEPARTMENTS

Raymond A. Frizzell, Ph.D., Richard Beatty Mellon Professor and Chair

DEPARTMENT PROFILE

The Department of Cell Biology and Physiology supports a diverse research portfolio, ranging from the study of fundamental cellular processes to structural mechanisms of protein interaction and the regulatory mechanisms that govern complex physiological processes in mammalian organisms. Research in the department is focused on four major areas: function and dysfunction of ion channels, cell polarity and the membrane traffic of proteins and lipids, reproductive biology, and signal transduction in diabetes and metabolism. The department houses the Center for Biologic Imaging, the Cystic Fibrosis Research Center, and the Center for Research in Reproductive Physiology. Faculty members contribute to research outside the department involving cancer; diabetes; and cardiovascular, renal, and other diseases. The department’s grant revenue has tripled since 1995; it has established core facilities for imaging, quantitative assay of molecular expression, and protein biochemistry; and the diversity of its research has been nourished by the steady recruitment and mentoring of new junior faculty.

Graduate Training

Selected Research Highlights

The graduate program in cell biology and physiology is focused on cell and integrative biology, combining the tools of systems biology, genetics, molecular biology, and biochemistry to understand the functions of cells and organisms. This central theme plays out in research focused on various diseases, including heart disease, cancer, diabetes, and inherited disorders of developmental and reproductive functions. The department brings together basic science and clinical research faculty and offers training opportunities far beyond the classroom through participation in journal clubs, research conferences, and national and international meetings.

Jennifer C. Condon, Ph.D., and

colleagues are elucidating the molecular events involved in maintaining uterine quiescence during pregnancy and isolating the triggers for uterine contractions at term. To better understand fetal regulatory mechanisms that time labor’s onset, they are studying fetal cell trafficking to the maternal uterus with the idea that fetal cell migration is critical in triggering the onset of labor. Condon and collaborators have discovered that fetal lung maturation activates fetal cells to migrate into the pregnant uterus, where they trigger an inflammatory reaction that ultimately leads to labor. The research team is now working to engineer fetalspecific knockout mice to identify the labor-related triggers, and it has initiated additional collaborations to confirm its findings in humans. Condon and colleagues hope that by understanding the events leading to uterine contraction during pregnancy they can reduce the incidence of preterm labor.

Successful cryopreservation of gonadal tissue is critical for fertility preservation via germ cell or testicular tissue transplantation. Stefan Schlatt, Ph.D., and his research team are developing tools to preserve fertility in cancer patients who receive treatment before puberty. The researchers have optimized protocols in primate testicular tissues and determined that cryopreservation of immature primate testis is a feasible approach to maintain spermatogonial stem cells. The ability to delay transplantation of cooled samples suggests an option for clinical centralization of testicular tissue cryopreservation and may serve as a means to preserve fertility of prepubertal boys undergoing chemotherapy. Schlatt’s studies provide a better understanding of testicular stem cells’ regulation and function and open the way toward preclinical studies to preserve male fertility during cancer treatment. Yong Wan, Ph.D., and colleagues are

studying the role of ubiquitindependent proteolysis in biological regulation. Skp2, a ubiquitin ligase subunit, facilitates cell cycle progression via degradation of various protein targets. The researchers found that cellular stimulation by the cytokine TGF-beta rapidly degrades Skp2, thus blocking cell-cycle progression and promoting cell-cycle arrest. Wan and colleagues also found that blocking Skp2 degradation greatly reduces TGF-beta-induced cell cycle arrest. These results identify a novel mechanism for tumor suppression using TGF-beta and provide an explanation for why dysfunction of the TGF-beta pathway has been associated with cancer.

Anthony J. Zeleznik, Ph.D., and

colleagues are studying the physiology and cell biology of ovarian function. Granulosa cells, which produce steroids and are associated with oocyte development, express the closely related orphan nuclear receptors steroidogenic factor-1 (SF-1) and liver receptor homolog-1 (LRH-1). To determine whether SF-1 and LRH-1 have differential effects on steroid production, Zeleznik and colleagues compared the effects of LRH-1 and SF-1 overexpression on estrogen and progesterone production by undifferentiated rat granulosa cells. Neither LRH-1 nor SF-1 alone stimulated estrogen or progesterone production; however, when combined with follicle stimulating hormone (FSH) and testosterone, each significantly increased progesterone production, with SF-1 having a greater effect. LRH-1 did not augment FSH-stimulated estrogen production; and SF-1 produced a slight, but not significant, increase of FSH-stimulated estrogen production. These findings demonstrate that LRH-1 and SF-1 have qualitatively similar actions on FSH-stimulated estrogen and progesterone production, which would suggest that these factors may have overlapping actions in steroidogenesis regulation accompanying granulosa cell differentiation. Hormones have been suggested to play a role in cell-cell communication by influencing the availability of gap junction proteins at the cell surface. Sandra A. Murray, Ph.D., and her laboratory have conducted in vivo and in vitro examinations of the ability of adrenocorticotropin (ACTH) to affect gap junctions in adrenal cells. ACTH treatment increased the size and number of gap junction plaques on cell membranes in hypophysectomized animals and in adrenal culture, and intracellular (cytoplasmic) annular gap junctions were observed in both

models. To investigate the relationship of annular gap junctions to surface junctions, cultured adrenal cells were transfected with cDNA encoding a green fluorescent protein tagged connexin 43 construct (Cx43-GFP) and studied by timelapse video microscopy, immunocytochemistry, and transmission electron microscopy (TEM). Internalization of part or all of a surface gap junction plaque resulted in annular gap junction formation. These studies support the hypothesis that cytoplasmic vesicles, initially described with TEM methods, can result from removal of gap junction plaques from the cell surface and indicate that this hormonally sensitive process might provide a method to alter intercellular communication.

Centers Center for Biologic Imaging Simon C. Watkins, Ph.D. Director Cystic Fibrosis Research Center Raymond A. Frizell, Ph.D. Director Center for Research in Reproductive Physiology Tony M. Plant, Ph.D. Director

Regular Faculty Endowed Chair Raymond A. Frizzell, Ph.D. Richard Beatty Mellon Professor and Chair Professors Sandra A. Murray, Ph.D. Tony M. Plant, Ph.D. Guy Salama, Ph.D. Simon C. Watkins, Ph.D. Anthony J. Zeleznik, Ph.D.

Associate Professors Daniel C. Devor, Ph.D. Vernon L. Gay, Ph.D. Kathleen D. Ryan, Ph.D. Stefan Schlatt, Ph.D. Linton M. Traub, Ph.D. William H. Walker, Ph.D. Allan Z. Zhao, Ph.D. Research Associate Professor Abhiram Sahu, Ph.D. Assistant Professors Meir Aridor, Ph.D. Jennifer C. Condon, Ph.D. Carolyn B. Coyne, Ph.D. Peter F. Drain, Ph.D. Georgia K. Duker, Ph.D. Yang Hong, Ph.D. Sanford H. Leuba, Ph.D. Patrick H. Thibodeau, Ph.D. Yong Wan, Ph.D. Research Assistant Professors Catherine Jackson Baty, Ph.D. Carol A. Bertrand, Ph.D. Michael Bruce Butterworth, Ph.D. Jens Ehmcke, Ph.D. Jeyasuria Pancharatnam, Ph.D. Kathryn W. Peters, Ph.D. Suresh Ramaswamy, Ph.D. Pedro Rodriguez-Collazo, Ph.D. Bela Schmidt, Ph.D. Donna B. Stolz, Ph.D. Fei Sun, M.D., Ph.D. Prakash C. Viswanathan, Ph.D.

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CRITICAL CARE MEDICINE

Ivet Bahar, Ph.D., John K. Vries Professor and Chair

Ann E. Thompson, M.D., Professor and Interim Chair

DEPARTMENT PROFILE

Created in October 2004, the Department of Computational Biology pursues three areas of specialization: computational structural / molecular biology, bioinformatics, and systems or mathematical biology. The department’s mission is to develop new computational models and methods for simulating complex biological processes, to advance the scientific understanding of biological systems through computational tools and theoretical approaches, to design new computational/mathematical models and methods for simulating complex biological processes, and to play a leading role in launching educational programs in computational biology and bioinformatics. Research in the department integrates biological, biomedical, computational, physical, mathematical, and engineering sciences to formulate and solve critical biological problems.

Graduate Training

Selected Research Highlights

The department’s educational mission is to introduce computational biology problems and methods to chemistry, physics, engineering, mathematics, and computer sciences students as well as to provide basic physical, engineering, and computational background to biology and biomedical sciences students to tackle complex biological problems on a computer by managing and integrating databases and by simulating biological phenomena at different levels. Students are trained through the Joint Program in Computational Biology, a collaboration with Carnegie Mellon University; the Molecular Biophysics and Structural Biology Program; and the Interdisciplinary Biomedical Graduate Program.

Ivet Bahar, Ph.D., and her laboratory study the dynamics and machinery of supramolecular protein complexes. They have explored equilibrium motions of proteins that exhibit relatively large conformational changes upon protein binding using the Gaussian and anisotropic network model of protein dynamics. These studies emphasize the preexisting equilibrium/conformational selection as a mechanism for protein-protein interaction and lend support to the concept that proteins, in their native conformation, are predisposed to structural fluctuations that are relevant to, or even required for, biological functions. Bahar and colleagues have shown that equilibrium motions also determine communication patterns, which can be delineated by spectral graph methods applied to biomolecular structures. Applications to a series of allosteric systems demonstrate that key mechanical sites (e.g., hinge centers) and functional regions (e.g., adenosine triphosphate [ATP] binding sites, catalytic residues) are distinguished by their enhanced signal transduction propensities. Efficient communication through a network of key residues thus emerges as a required property for mediating allosteric responses. These observations suggest that biomolecular structures have evolved to facilitate the collective dynamics and allosteric communication mechanisms required to achieve appropriate biological function.

Panayiotis V. Benos, Ph.D., and colleagues have conducted a detailed analysis of transcription factor (TF) proteins, which recognize limited DNA sequences with high specificity and control the expression of surrounding genes. A number of studies have attempted to use TF binding preference to predict new target sites, but the distance metrics and alignment algorithms used to compare the binding profiles have not been fully explored or optimized. Benos and colleagues evaluated various comparison metrics and alignment algorithms, being careful to include not only structural information but also distinctions between subfamilies in predicting the identity or structural class of a protein. The researchers found that local alignments were better than global alignments at detecting eukaryotic DNA motif similarities and tested multiple alignment strategies for binding profile and tree-building method efficiency. They also developed a new method to automatically determine the optimal number of clusters and apply it to constructing a new set of familial binding profiles to improve TF classification accuracy. Benos and colleagues then combined all of these testing methods into a software tool called STAMP, which is now available publicly. Detecting similarities between DNA motifs is critical for comparative study of transcriptional regulation. The tools developed by these researchers offer a strong foundation for future transcriptional modeling studies.

MicroRNAs (miRNAs) are a type of small RNAs thought to negatively regulate protein production; furthermore, aberrant expression of miRNAs is linked to cancer and other diseases. Using a new computational method called K-Factor, Bino John, Ph.D., and colleagues have identified numerous upstream regulatory elements that are likely essential to the transcriptional and posttranscriptional regulation of

miRNAs. K-Factor is unique in that it can predict regulatory motifs in functionally related sequences without relying on evolutionary conservation. The researchers noted that the regulatory motifs appear frequently, exist in multiple copies, and are highly enriched in G and C nucleotides. John and colleagues also determined that certain diseaseassociated transcription factors appear to contribute to abnormal miRNA expression in diseases like cancer. After further examination, the researchers found that the transcription factors c-Myb, NF-Y, Sp-1, MTF-1, and AP-2a are all master regulators of miRNA expression. Based on these results, John and colleagues concluded that focused studies of miRNA-regulating transcription factors will be critical in developing treatment for miRNArelated diseases.

Regular Faculty Endowed Chair Ivet Bahar, Ph.D. John K. Vries Professor and Chair Professor Hagai Meirovitch, Ph.D. Associate Professors Carlos J. Camacho, Ph.D. John K. Vries, M.D. Assistant Professors Panayiotis V. Benos, Ph.D. Bino John, Ph.D. Ivan Viktorovich Maly, Ph.D. Daniel M. Zuckerman, Ph.D.

DEPARTMENT PROFILE

In January 2002, the School of Medicine established the first Department of Critical Care Medicine at a U.S. medical school. The department is a natural extension of the work begun by the late Peter Safar, M.D., a pioneer in the field of critical care medicine, and further developed by Ake Grenvik, M.D., Ph.D., in the former Department of Anesthesiology and Critical Care Medicine. The decision to spin off critical care medicine into an independent department, under the founding chairmanship of Mitchell P. Fink, M.D., solidified the school’s leading role in this field. Each year, the department trains more than 30 fellows in adult and pediatric critical care medicine, oversees $42 million in research grants, and routinely cares for patients in 13 different intensive care units at the various Oakland hospitals.

Residency and Fellowship Training

Since 1963, the Multidisciplinary Critical Care Training Program, which is now part of the Department of Critical Care Medicine, has trained more than 600 intensivists — physicians who specialize in the management of critically ill patients in hospital intensive care units (ICUs). The program combines critical care fellowships in anesthesiology, medicine, and surgery and provides a broad, patient-centered curriculum in medical, cardiac, surgical, cardiothoracic, burn, trauma, transplantation, neurovascular, obstetric, and pediatric critical care. Senior fellows may participate in laboratory research, clinical investigation, ICU administration, critical care ethics, and additional clinical training. Selected Research Highlights

Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that has been shown to improve short-term outcomes for hypoxemic respiratory failure in full-term neonates. Derek C. Angus, M.B.Ch.B., M.P.H., and colleagues are extending these earlier findings to include a randomized controlled trial of 36-week (post-conception) preterm newborns with respiratory failure to determine the treatment efficacy of iNO for them. Respiratory failure in premature infants has a different etiology than respiratory failure in full-term infants and includes a wide

array of long-term consequences. Angus and his team hope to determine whether iNO is a viable treatment option for prematurity-associated respiratory failure in both the shortand long-term care of critically ill infants. This study is generating contemporary data on the long-term consequences of prematurityassociated respiratory failure and the effects of iNO. It follows newborn to school-age children, examining survival, neurobehavioral and social development, and the effect on families. The study will aid future trials by providing information about the appropriate follow-up duration and the robustness of surrogate endpoints. Patrick M. Kochanek, M.D., is

conducting preclinical testing of novel nitroxide-based resuscitation strategies for combined head injury and hemorrhagic shock, a common but challenging form of combat casualty. The rising incidence of improvised explosive devices in combat arenas (as well as in terrorist attacks in the civilian sector) increases the need for this type of intervention. Because hemorrhagic shock exacerbates damage in traumatic brain injury, first-responders in battle must administer an effective resuscitation fluid. Currently used fluids can contribute to brain swelling after head trauma and are relatively ineffective. Kochanek and others at the Safar

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D E R M ATO LO GY

continued

Louis D. Falo Jr., M.D., Ph.D., Professor and Chair

Center for Resuscitation Research believe that a nitroxide-based resuscitation fluid will offer important advantages over conventional fluids in the resuscitation of head trauma/ hemorrhagic shock patients. To establish the efficacy of this treatment, they are using a rat model to test a battery of nitroxide-based resuscitation fluids. Additional applications of this research include treatment of traumatic brain injury from motor vehicle accidents and other causes. Severe sepsis, which can cause acute onset of organ failure as a result of bloodstream infection, is a major health problem that kills nearly 250,000 Americans each year and costs billions of dollars; available therapies for sepsis are suboptimal. John A. Kellum Jr., M.D., and Gilles Clermont, M.D.C.M., are working with a multidisciplinary team of basic and clinical researchers, bioengineering and biomaterials experts, and complex systems modelers to design and test an extracorporeal device for treating severe sepsis using hemoadsorption to remove inflammatory mediators from blood. The team has developed a cytokine capture model as well as a mathematical model of blood purification in sepsis. Kellum, Clermont, and their collaborators are testing device prototypes in animals and using human whole blood to design the novel therapeutic device. Robert S.B. Clark, M.D., is compiling

age-specific therapeutic strategies for clinical trials aimed at improving outcome in infants and children after cardiopulmonary arrest, which often leads to hypoxic-ischemic encephalopathy (HIE), a form of perinatal asphyxia that causes permanent brain damage. In the United States, 87 percent of children with unexpected cardiopulmonary arrest die each year, and nearly 50 percent of the survivors have severe brain

damage. These outcomes reflect the fact that, to date, there are no interventions to reverse HIE’s cellular consequences. Adult clinical trials suggest that some post-arrest HIE can be prevented by immediate hypothermia. In adults, however, cardiopulmonary arrest has a cardiac etiology, whereas in infants and children, asphyxia is the principal cause. To investigate the underlying mechanisms and evaluate therapeutic interventions, Clark’s laboratory has developed an age-appropriate model of pediatric asphyxial cardiac arrest in rats. Preliminary data confirm that post-resuscitative hypothermia helps to attenuate neurological deficits. In addition, the model allows physiologic monitoring, biochemical and cellular assessment, and functional outcome assessment for further development of acute therapies and chronic rehabilitation strategies for cardiac arrest and HIE.

Center Safar Center for Resuscitation Research Patrick M. Kochanek, M.D. Director

Regular Faculty Endowed Chair Mitchell P. Fink, M.D. Watson Professor of Surgery and Professor of Critical Care Medicine Distinguished Service Professor Ake Grenvik, M.D., Ph.D. Professors Derek C. Angus, M.B.Ch.B., M.P.H. Lakshmipathi Chelluri, M.D. Joseph M. Darby, M.D. Michael A. DeVita, M.D. John A. Kellum Jr., M.D. Patrick M. Kochanek, M.D. Peter K. Linden, M.D., D.M.D. G. Daniel Martich, M.D. Richard A. Orr, M.D. Michael R. Pinsky, M.D. Paul L. Rogers, M.D. Carl A. Sirio, M.D., M.P.H. Ann E. Thompson, M.D. Shekhar T. Venkataraman, M.D.

Associate Professors Marie R. Baldisseri, M.D. Arthur J. Boujoukos, M.D. Joseph A. Carcillo Jr., M.D. Robert S.B. Clark, M.D. Gilles Clermont, M.D.C.M. David Wayne Crippen, M.D. Russell L. Delude, Ph.D. Ricardo Alfonso Munoz, M.D. Juan C. Puyana, M.D. Armando J. Rotondi, Ph.D. Assistant Professors Ruben A. Abunto Jr., M.D. Adam S. Akers, M.D. Ali Al-Khafaji, M.B.Ch.B. Louis H. Alarcon, M.D. Rajesh K. Aneja, M.B.B.S., M.D. Hulya Bayir, M.D. Lillian Liang Emlet, M.D. Kathryn A. Felmet, M.D. Melinda Fiedor Hamilton, M.D. Ericka L. Fink, M.D. Scott R. Gunn, M.D. John Robert Hotchkiss Jr., M.D. David Tom Huang, M.D. Ata Murat Kaynar, M.D. Eric M. Milbrandt, M.D. Linas Mockus, M.D. Jason E. Moore, M.D. David M. Muigai, M.B.Ch.B. Holt Nicholas Murray, M.D. Raghavan Murugan, M.B.B.S. Anton Cristian Nicolescu, M.D. Penny L. Sappington, M.D. Kai Singbartl, M.D. Raghukumar Deenadayalan Thirumala, M.B.B.S. Robert S. Watson, M.D., M.P.H. Sachin Purushottam Yende, M.B.B.S.

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DEPARTMENT PROFILE

The Department of Dermatology’s threefold mission is to develop the highest quality patient care, train outstanding residents in clinical care and research, and advance the science of dermatology and cutaneous biology through innovative research programs. The department offers an array of clinical services in general dermatology, medical dermatology, pediatric dermatology, dermatologic surgery, dermatopathology, cutaneous oncology, and cosmetic aesthetic dermatology. Research in the department spans a broad range of basic science investigations and clinical research in immunotherapy, improved diagnostics, and patient education.

Residency and Fellowship Training

The dermatology residency program is designed to develop expertise in the diagnosis and management of all dermatologic conditions. A combined investigative/academic residency track within the traditional residency program combines clinical training with advanced fellowship training in a clinical, basic science, epidemiologic, or educational area of pursuit. The dermatopathology fellowship enables participants to master routine diagnoses while gaining experience with diverse histologic specimens and a full range of molecular and histologic diagnostic techniques. The dermatologic surgery fellowship encompasses general dermatologic surgery, cutaneous surgical oncology, and Mohs surgery, as well as experience in cosmetic surgery, aesthetic procedures, and laser surgery.

potency can be attributed to the action of skin dendritic cells. These cells normally transport a foreign body to the lymph nodes, where other dendritic cells present the invader to T cells, thus triggering an immune response. In the case of lentiviral vectors, however, the skin dendritic cells carry the vectors to the lymph nodes and follow through with presentation to T cells. The immune response triggered by the skin dendritic cells’ lentiviral presentation is more robust than with traditional vaccines and occurs after only one antigen exposure. In addition, the lentiviral vector does not produce an immune response on its own, even though it is technically a foreign body. Therefore, the vector can be used as a vehicle for a number of different vaccines without triggering its own immune response and eliminating its usefulness as a vehicle.

Selected Research Highlights Drazen M. Jukic, M.D., Ph.D., and Louis D. Falo Jr., M.D., Ph.D., and

Research Assistant Professor Runkuan Yang, M.D., Ph.D. Visiting Instructors Queenie M. D’Costa, M.B.B.S. Michael Charles Reade, M.B.B.S. Erik Ryan Su, M.D.

Laura K. Ferris, M.D. Ph.D., are devel-

colleagues have developed a novel method for vaccine delivery that can boost immune response to a particular antigen after just one exposure. In their study, immunization halted the progression of melanoma and significantly increased survival in a mouse model. The technique employs an inactivated retrovirus, in this case a modified lentiviral vector, that can be used as a carrier to deliver the antigen of interest to the immune system. The lentiviral-based vaccine’s

oping software for a computer-aided approach to improve both precision and accuracy of pigmented skin lesion diagnoses. The researchers have already developed and used this approach for the analysis of dermatopathologic and pathologic images and want to expand the technique to assist both the clinician and pathologist in better assessing lesions of unknown pathology using a database with clinicopathologic correlations. The technique is called interactive search-assisted diagnosis (ISAD) and

can be used to evaluate pigmented cutaneous lesion images. Jukic and Ferris are developing the search capability through a collaboration with Intel Research Pittsburgh and Carnegie Mellon University using an open-source software prototype called Diamond. The researchers plan to deliver an information technology tool that provides greater precision in screening pigmented lesions and that is also useful across the board for primary care physicians, general pathologists, dermatologists, and dermatopathologists who could use ISAD methods. CD4+ T cells are classified as Th1 cells and induce a cellular immunity known as Th1-type immunity that, if deficient in cancer patients, could facilitate tumor progression and limit the effectiveness of immunotherapeutic approaches. Walter J. Storkus, Ph.D., Amy K. Wesa, Ph.D., and colleagues believe that type-1 polarized dendritic cells (DC1) might recondition patient antitumor CD4+ T-cell responses toward Th1-type immunity. The researchers found that stimulation of CD4+ T cells with peptide-pulsed DC1 promoted robust Th1-type, epitope-specific T-cell responses. In addition, DC1based stimulation seemed capable of revitalizing defective Th1-type responses within a subset of antigen-experienced CD4+ T cells in melanoma patients. Overall, the DC1-based stimulation promoted elevated levels of IFN-gamma from responder CD4+ T cells and led to increased levels of the IL-12Rbeta2 gene and T-bet expression by Th cells. These results suggest that preexisting CD4+ T-cell immunity to cancer may be corrected via the application of DC1-based vaccination protocols.

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Paul M. Paris, M.D., Professor and Chair

EMERGENCY

DEPARTMENT PROFILE

Regular Faculty Professors Jau-Shyong Deng, M.D. Louis D. Falo Jr., M.D., Ph.D. Walter J. Storkus, Ph.D. Associate Professor Joseph Cornelius English III, M.D. Assistant Professors Adriana L. Larregina De Morelli, M.D., Ph.D. Geza Erdos, Ph.D. Laura K. Ferris, M.D., Ph.D. Larisa Geskin, M.D. Yukai He, M.D., Ph.D. Drazen M. Jukic, M.D., Ph.D. Grace Jung Lee, M.D. Suzan Obagi, M.D. Timothy J. Patton Jr., D.O. Arash Radfar, M.D., Ph.D. Zhaoyang You, Ph.D. Visiting Assistant Professors Mary Patrice Counihan, M.D. Alexandra Yan Zhang, M.D. Instructor Maja Mandic, M.D. Visiting Instructors Jonhan Ho, M.D. Jennifer Lynn Taylor, Ph.D. Amy K. Wesa, Ph.D.

The Department of Emergency Medicine is dedicated to improving the outcomes of acutely ill and injured patients through high quality, cost-effective care, education, and research. The specialty of emergency medicine has a unique position in the health care system because of its involvement in prehospital programs and because it is often the door to the institution. Forty percent of all patients admitted to UPMC receive their first care in the emergency department. Synergistic efforts among department faculty; local emergency medical services personnel; and the Center for Emergency Medicine, a multihospital consortium in western Pennsylvania aimed at advancing emergency medicine, have enabled the department to provide outstanding academic programs. One of the department’s current research projects is a collaborative study with the Department of Critical Care Medicine of optimal early sepsis care, including the biology and genetics involved in patient outcomes.

Residency and Fellowship Training

Selected Research Highlights

The University of Pittsburgh Affiliated Residency in Emergency Medicine is a three-year program to train emergency physicians in clinical care, research, teaching, and administration. UPMC, Mercy Hospital of Pittsburgh, and Western Pennsylvania Hospital jointly sponsor the program. In addition, emergency care is provided at Children’s Hospital of Pittsburgh of UPMC and affiliated community and specialty hospitals. Together, these facilities serve more than 170,000 emergency patients per year. Residents have at their disposal the resources of the Center for Emergency Medicine and its air medical transport system (STAT MedEvac), the Bureau of Emergency Medical Services of the City of Pittsburgh, the Pittsburgh Poison Center, and the School of Medicine. The program provides training in internal medicine, surgery, anesthesia, pediatrics, orthopaedics, critical care, emergency medical care in prehospital and hospital settings, as well as service with STAT MedEvac and experience in clinical and basic research. The department also offers board-approved fellowships in research and emergency medical services. All fellows are required to participate in research and to obtain an advanced degree in an appropriate field.

Many low-risk patients with pneumonia are hospitalized despite recommendations to treat such patients in an outpatient setting. Donald M. Yealy, M.D., and colleagues have analyzed data collected by retrospective chart review for lowrisk patients (pneumonia severity index [PSI] risk classes I to III without evidence of arterial oxygen desaturation) who were enrolled in a cluster-randomized trial conducted in 32 emergency departments. The researchers found that 44.7 percent of all low-risk patients were treated as inpatients. Factors independently associated with increased odds of hospitalization included PSI risk classes II and III, the presence of medical or psychosocial contraindications to outpatient treatment, comorbid conditions, multilobar radiographic infiltrates, and home therapy with oxygen, corticosteroids, or antibiotics before presentation. Although some inpatients did exhibit a true contraindication to outpatient treatment, 20.1 percent had no identifiable risk factors other than PSI risk class II or III. Based on these results, Yealy and colleagues concluded that hospital admission appears to be justified for one-third of low-risk

inpatients based on the presence of one or more contraindications to outpatient treatment. However, at least one-fifth of low-risk inpatients did not have a contraindication to outpatient treatment or an identifiable risk factor for hospitalization, suggesting that treating those patients in an outpatient setting would not adversely affect patient outcomes. Previous research by Clifton W. Callaway, M.D., Ph.D., and colleagues has shown that inducing hypothermia of 32º to 34ºC after resuscitation from cardiac arrest improves neurologic recovery. The researchers have conducted a follow-up study to establish optimal cooling levels. Using a rat model of asphyxial cardiac arrest, Callaway and colleagues tested post-resuscitation temperatures of 33º, 35º, or 37ºC using computercontrolled cooling fans and heating lamps. Neurologic scores were measured daily, and histologic analysis was conducted at 14 days post-intervention. The researchers found that neurologic scores were poorest for rats in the 37ºC group compared to the other two hypothermia groups on days one through three. In addition, hypothermia increased the number of surviving neurons, with no difference between the groups cooled to 33º and 35ºC. Callaway and colleagues concluded that hypothermia improves neurologic scores and neuronal survival following cardiac arrest in rats with little to no measurable difference in outcomes among the exact temperatures used to achieve hypothermia.

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James J. Menegazzi, Ph.D., and

colleagues have demonstrated that using cardiopulmonary resuscitation (CPR) as a first intervention for prolonged ventricular fibrillation is more effective than proceeding directly to countershock. However, poor quality CPR has been associated with poorer patient outcomes. With these findings in mind, Menegazzi and colleagues examined the quality of CPR delivered on the floor compared with CPR delivered on a moving stretcher. Teams were assigned to perform two-rescuer CPR on a recording resuscitation mannequin on the floor or on a moving stretcher. After a five-minute rest, the teams performed CPR under the opposite condition. Compression and ventilation data were collected and included compression depth, compression rate per minute, percentage of correct chest compressions, tidal volume, and percentage of correct ventilations. The percentage of correct compressions and depth of compressions was much greater when performed on the floor than on a moving stretcher. In addition, the percentage of correct ventilations, although not the number of ventilations, was greater when performed on the floor than on a moving stretcher. Menegazzi and colleagues concluded that CPR quality is significantly compromised while in motion, a finding that could assist hospital personnel and first responders in taking steps to ensure the best possible outcome for patients.

Regular Faculty Endowed Chairs Clifton W. Callaway, M.D., Ph.D. Ronald D. Stewart Professor of Emergency Medicine Research

ERMI Paul Paris Chair in Emergency Medicine Quality (open) Professors Paul M. Paris, M.D. Ronald N. Roth, M.D. Allan B. Wolfson, M.D. Donald M. Yealy, M.D. Research Professor James J. Menegazzi, Ph.D. Associate Professors Susan M. Dunmire, M.D. Charles C. King, M.D. John F. Mahoney, M.D. Vincent N. Mosesso Jr., M.D. Kevin S. O’Toole, M.D. Assistant Professors Jawaid Akhtar, M.B.B.S. John S. Cole, M.D. Michele L. Dorfsman, M.D. Thomas J. Doyle, M.D. Stephanie Marie Gonzalez, M.D. Francis X. Guyette III, M.D. Scott T. Harrington, M.D. Margaret Hsieh, M.D. Kenneth D. Katz, M.D. Julie B. McCausland, M.D. Charissa Pacella, M.D. Paul E. Phrampus, M.D. Jon Charles Rittenberger, M.D. Joe Suyama, M.D. Henry E. Wang, M.D. Research Assistant Professors David P. Hostler III, Ph.D. Paul Daniel Patterson, Ph.D. Instructors Robert Donald Cannon, D.O. Gwendolyn Marie Lewis, M.D. Anthony F. Pizon, M.D. Research Instructor Brian Paul Suffoletto, M.D.

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Jeannette E. South-Paul, M.D., UPMC Andrew W. Mathieson Professor and Chair

Olivera J. Finn, Ph.D., Professor and Chair

DEPARTMENT PROFILE

The Department of Family Medicine teaches medical students the basic tenets of family medicine by modeling universally valued competencies in patient care with a focus on high quality, familycentered primary care. Community-based research in primary care, prevention, and clinical epidemiology explores barriers to immunization and management of chronic disease through the department’s Center for Primary Care Community-Based Research (CPCR). The center aims to improve the health of community residents by promoting patient education, adherence to disease prevention and treatment strategies, and research networking and collaboration among primary care disciplines in particular disease areas. Diabetes, stroke, cardiovascular disease, physician-patient communication, and prostate cancer are among CPCR’s current externally funded clinical project areas. The department’s clinical division provides care in various local communities, including the Hill District, Squirrel Hill, Bloomfield, Lawrenceville, Garfield, Hazelwood, McKeesport, and New Kensington. Underserved population care, primary care sports medicine, comprehensive family care, and health care team coordination are additional focal areas.

Residency and Fellowship Training

Selected Research Highlights

The department provides leadership for family medicine residency programs at UPMC St. Margaret, UPMC Shadyside, and UPMC McKeesport, which also serve as the primary clinical sites for medical student education in family medicine. The UPMC Consortium of Family Practice Residencies and Affiliates serves as a collegial academic forum for faculty from the three UPMC residency programs, three affiliated residency programs, and the department. In collaboration with the residency programs at UPMC St. Margaret, UPMC Shadyside, and UPMC McKeesport, the department offers accredited primary care sports medicine fellowships as well as geriatrics fellowships. UPMC St. Margaret also offers a faculty development fellowship concentrating on the clinician educator.

Donald B. Middleton, M.D., is

evaluating ways to increase the proportion of hospital inpatients vaccinated against pneumococcal infection by establishing a standing orders program (SOP) to vaccinate patients over 65 and those with a chronic condition predisposing them to pneumococcus. With SOP, the nursing staff screens new admissions and places a pre-printed order form for the pneumococcal polysaccharide vaccine (PPV) in the charts of eligible patients. Following a physician’s order, the nursing staff administers and records the PPV. Middleton notes that using electronic medical records can significantly improve the assessment and documentation of patient vaccination status. He hopes to identify and provide recommendations for overcoming barriers to establishing SOP in acute care inpatient facilities. Middleton has found that vaccination rates in hospitals with SOPs are generally higher than in hospitals requiring individual physician orders.

Although colorectal cancer is a leading cause of cancer-related deaths in the United States, screening rates are low. Richard K. Zimmerman, M.D., M.P.H., is studying the determinants of colorectal cancer screening to assess what interventions might increase these rates. Using patient records, he considers factors like geography, socioeconomic status, and practice setting as well as number of office visits, type of visit, immunizations, and cancer tests given. In this study, the fecal occult blood test (FOBT) was the primary screening method, followed by the endoscopy/ barium enema and colonoscopy. Factors that Zimmerman suggests are barriers to intervention are cost, access to screening, and productivity incentives for providers (seeing more patients equals less time per patient). He recommends that clinicians mail reminders to patients, perhaps combining reminders for mammograms, vaccinations, and cancer screenings into one card. In addition, FOBT screenings could coincide with influenza vaccine clinics (or other yearly contacts) in an effort to increase patient screening rates.

DEPARTMENT PROFILE

Center Center for Primary Care Community-Based Research Jeannette E. South-Paul, M.D. Director

Regular Faculty Endowed Chair Jeannette E. South-Paul, M.D. UPMC Andrew W. Mathieson Professor and Chair Professors Donald B. Middleton, M.D. Richard K. Zimmerman, M.D., M.P.H. Associate Professor Andrea R. Fox, M.D. Visiting Associate Professor Charles W. Mackett III, M.D. Assistant Professors Ya’aqov M. Abrams, M.D. Danforth N. Lincoln, M.D. Karen Melissa Moyer, M.D. Dawna Hoyle Woodyear, M.D. Yaqin Xia, M.D. Visiting Assistant Professors James C. Dewar Jr., M.D. Lauracinne D. Jenkins, M.D. Robert William Smith, M.D. Michael A. Yonas, Dr.P.H., M.P.H.

Jeannette E. South-Paul, M.D.,

and colleagues are conducting a community-based pilot study to examine the barriers to care for pregnant teens in Allegheny County. These barriers can include financial considerations, regulations regarding parental notification, access to health care facilities, and knowledge about the importance of early prenatal care. Consequently, pregnant teens often experience premature labor, and their offspring are at greater risk for low birth weight, infant mortality, and delays in behavioral and cognitive development. Given these risk factors, the research team is also expanding the pilot study to determine what changes could be implemented to promote longer pregnancy spacing (time between pregnancies) for teens.

Research Assistant Professor Mary P. Nowalk, Ph.D.

Although the Department of Immunology was not established until January 2002, the University has a long-standing history of excellence in immunology research and training. Jonas Salk, Niels Jerne, Frank Dixon, Thomas E. Starzl, Julius S. Youngner, and Ronald B. Herberman are just some of the leaders in immunology who have served — or are continuing to serve — on Pitt’s faculty. Current immunology research maintains the tradition of excellence through the work being done in transplant immunology, autoimmunity, cancer immunology, viral immunology (HIV/AIDS), and immunology of infectious disease. When it was established, the department recruited a core of senior faculty members to provide a strong foundation for immunology research. It is now ensuring continued proficiency and growth in basic immunology research through the recruitment of talented young immunologists involved in the newest areas of investigation — the development, genetics, and molecular mechanisms of the immune response — and through the work of an extensive group of secondary faculty, most of whom come from the Departments of Medicine, Surgery, Molecular Genetics and Biochemistry, and Pathology.

Graduate Training

Selected Research Highlights

Immunology is one of the concentrations offered through the medical school’s Interdisciplinary Biomedical Graduate Program. The curriculum provides broad exposure to a variety of biomedical fields in the first year, followed by concentrated studies in a particular field—immunology, in this case—in subsequent years. Immunology affects many aspects of health and disease, and program faculty often hold additional appointments in other medical school departments, the University of Pittsburgh Cancer Institute, or the Thomas E. Starzl Transplantation Institute. The diversity of faculty backgrounds strengthens the program and broadens the research and academic experiences available to students.

V(D)J recombination is a site-specific DNA recombination mechanism used for immunological protection against attacks by bacterial, viral, and parasitic invaders and is necessary for recognition of diverse antigens. Lisa A. Borghesi, Ph.D., has shown that DNA rearrangements mediated by V(D)J recombination machinery are not restricted to B and T lymphocytes. Using a mouse model in which V(D)J recombination elicits green fluorescent protein (GFP) expression, Borghesi demonstrated that DNA rearrangements take place in natural killer (NK) cells and dendritic cells. Moreover, she has extended this finding to human NK cells. V(D)J recombinationdependent translocations are mechanistically associated with fatal B- and T-cell leukemias, raising the possibility that recombination errors may also contribute to cancers of the NK lineage.

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Steven D. Shapiro, M.D., Dr. Jack D. Myers Professor and Chair

Lawrence P. Kane, Ph.D., studies cooperation mechanisms between T-cell receptors (TCR) for antigen and “co-stimulatory” signaling pathways to control the activation and function of T cells. He is working to understand how the CD28 receptor cooperates with TCR to activate the transcription factor NF-kB, which is critical for mounting an immune response. Kane previously showed that this pathway involved the kinase Akt, and dysregulation has been implicated in tumorigenesis. Kane and his laboratory are also studying the biochemical mechanisms for T-cell costimulation by a novel regulatory receptor known as TIM-1. His research team was among the first to show that TIM-1 activates intracellular signaling pathways that cooperate with signals derived from TCR to increase the efficiency of T-cell activation. A better understanding of T-cell activation may lead to novel therapeutics for inappropriate or undesirable T-cell activation, as occurs in many autoimmune diseases and in organ transplantation. Binfeng Lu, Ph.D., is studying the molecular network that controls the initiation, effector function, and longterm fate of cell-mediated immune responses. He has demonstrated that a signaling cascade amplified and prolonged by Gadd45 proteins is operative in controlling many phases of a T cell’s life cycle. Using knockout mice lacking Gadd45b and Gadd45g genes, Lu has established a critical role of this signaling cascade in the initiation of cell-mediated immune responses during infection and tumor immunity. Paradoxically, while Gadd45b is important for the generation of the Th1 response, it also limits this response by causing effector T-cell death. The lack of Gadd45mediated self-limiting mechanisms

results in exuberant T-cell activation and autoimmunity. Lu hopes to elucidate the molecular and cellular mechanisms underlying tissue inflammation during the course of chronic diseases like autoimmune diseases and cancer. Karen A. Norris, Ph.D., uses mouse and primate models to examine immune responses to parasites and opportunistic infections. She studies Trypanosoma cruzi, a parasite that is transmitted by insect vectors and via blood transfusions and that causes Chagas disease, a potentially fatal illness prevalent in Latin America. Norris has developed a highly sensitive method for diagnosis of Chagas disease using a recombinant complement regulatory protein from the parasite; she is currently developing recombinant vaccines based on the complement regulatory protein and other parasite proteins. Norris has also made significant progress in examining pulmonary complications of AIDS using a primate model that produces pulmonary function changes due to persistent inflammatory responses to subclinical infections, as is commonly seen in HIV-infected patients. These studies should ultimately lead to interventions to prevent HIV-associated lung damage.

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Regular Faculty Professors Olivera J. Finn, Ph.D. Christine A. Milcarek, Ph.D. Associate Professors William H. Chambers, Ph.D. Penelope A. Morel, M.D. Karen A. Norris, Ph.D. Russell D. Salter, Ph.D. Assistant Professors Per H. Basse, M.D., Ph.D. Robert J. Binder, Ph.D. Lisa A. Borghesi, Ph.D. Kelly S. Cole, Ph.D. Lawrence P. Kane, Ph.D. Binfeng Lu, Ph.D. Research Assistant Professors Patrizia Fuschiotti, Ph.D. Juliet E. Wynn, M.D. Qin Yang, M.D.

The Department of Medicine is organized into the following divisions: Cardiology; Clinical Pharmacology; Endocrinology and Metabolism; Gastroenterology, Hepatology, and Nutrition; General Internal Medicine; Geriatric Medicine; Hematology / Oncology; Infectious Diseases; Pulmonary, Allergy, and Critical Care Medicine; Renal-Electrolyte; and Rheumatology and Clinical Immunology. The department and its divisions are turning from individual grant support to multidisciplinary program project and center grants to emphasize collaborative research so as to better understand many important diseases and translate this understanding into improved patient care. Educating the next generation of academic physicians is a priority for the department, which provides more than one-third of the teaching to medical students and offers postgraduate training at the residency and fellowship levels.

Residency and Fellowship Training

The Division of General Internal Medicine takes a lead role in developing and coordinating the series of training programs for the department; each subspecialty works closely with the programs to assure high quality education and access to faculty in each area. The General Internal Medicine Fellowship Program, which trains physicians dedicated to primary care, is divided into two tracks: the Clinical Research Training Program for physicians interested in research careers and the Clinician Educator Training Program for those who wish to pursue a career in medical education. In addition, the Geriatric Internal Medicine Residency Track is a flexible program providing specific training in the care and advocacy required for older adults. Analogously, the Medicine-Pediatrics Residency Training Program provides residents with the special skills required in caring for children. The Community-Based Categorical Residency Training Program at UPMC Shadyside prepares residents for work in primary care and numerous subspecialties by providing exposure to a variety of venues, including the VA Pittsburgh Healthcare System and the University of Pittsburgh Cancer Institute. The Primary Care Residency

Training Program prepares physicians for the challenge of primarily diagnosing and treating patients in an ambulatory setting; it emphasizes longitudinal and ambulatory care while also stressing the inpatient skills of an internist. The Women’s Health Training Program combines obstetrics, gynecology, psychiatry, and adolescent medicine into a multidisciplinary experience that prepares residents to provide a variety of routine health care and screening services to women. The Global Health Training Program allows residents to practice worldwide in both indigent and community settings with which the department and the University/UPMC have developed relationships. Residents may apply for additional training through the Biomedical Informatics Training Program, the Consortium Ethics Program, the Clinical Ethics Training Program, and the Mentorship Program Initiative. Divisions Cardiology Barry London, M.D., Ph.D. Chief

The Division of Cardiology operates clinically as the UPMC Cardiovascular Institute and specializes in congestive heart failure and cardiac transplantation; invasive cardiology, including

cardiac catheterization, percutaneous intervention, peripheral interventions (including carotid stents), and percutaneous closure of atrial septal defects; electrophysiology, including device placement and ablations; noninvasive imaging, including echocardiography, nuclear cardiology, computed tomography angiography, and multiplanar reformation; and preventive cardiology. Major division research foci include basic mechanisms underlying the pathogenesis of congestive heart failure; the molecular genetics of inherited forms of heart failure and sudden death; genetic factors predicting clinical outcomes and drug response in sudden death, heart failure, and coronary stent restenosis; vascular biology and atherosclerosis; novel cardiovascular imaging techniques, including molecular imaging; stem cells and gene therapy for myocardial infarction and heart failure; and identification of novel, noninvasive predictors of heart disease and methods of presymptomatic intervention. Active collaborations are under way with the Department of Cell Biology and Physiology; the Department of Molecular Genetics and Biochemistry; the Heart, Lung, and Esophageal Surgery Institute; the McGowan Institute for Regenerative Medicine; and the Graduate School of Public Health. Clinical Pharmacology Robert A. Branch, M.D. Chief

The division’s Center for Clinical Pharmacology (CCP) conducts preclinical and clinical research, drug development, pharmacotherapy evaluation, and clinical pharmacology education for medical students. Clinical service includes decision analysis and information technology that is used to evaluate pharmacotherapy within the UPMC system.

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CCP’s research program, which is supported by a well-equipped infrastructure, anchors a series of successful collaborations within and outside the University. Three major themes, each supported by multidisciplinary core laboratories and multiple partnerships, comprise CCP’s focus. The Preclinical Pharmacology Research Program and Core Labs focus on molecular and cellular preclinical pharmacology, organ/tissue preclinical pharmacology, and whole animal preclinical pharmacology. The Clinical Pharmacology Research Program and Core Labs conduct clinical research using high-throughput pharmacogenomics, pharmacokinetics, drug metabolism, and mass spectrometry-based metabolomics. The Drug Optimization Program and Information Technology/ Biostatistics Core provides clinical outcome-based information technology (IT) for decision analysis of clinical drug use and IT support to lab-based clinical research collaborative projects and grants. Endocrinology and Metabolism Andrew F. Stewart, M.D. Chief

The Division of Endocrinology and Metabolism focuses its clinical services on treating diabetes, obesity, hyperlipidemia, thyroid disorders, pituitary disease, osteoporosis and calcium disorders, phosphorus disorders, and male and female reproductive disorders. These services are delivered in part through the outpatient Center for Diabetes and Endocrinology at UPMC Presbyterian, the Shea Clinic at UPMC Shadyside, the Obesity and Nutrition Research Center, the Osteoporosis Prevention and Treatment Center, and through community-based clinics in Mt. Lebanon, Monroeville, and elsewhere. Division research is broad and

includes dietary and lifestyle management in obesity; coronary artery angioplasty and bypass surgery for diabetic patients; mechanisms that link body fat with insulin resistance; novel therapies for osteoporosis; development of methods to expand pancreatic beta cell numbers and function; gene therapy approaches to improve pancreatic islet transplantation; parathyroid-related protein for treatment of postmenopausal osteoporosis and its role in arterial restenosis following angioplasty; and animal models of obesity, type 1 and type 2 diabetes, and insulin and leptin action and resistance. Gastroenterology, Hepatology, and Nutrition David C. Whitcomb, M.D., Ph.D. Chief

The core clinical programs of the Division of Gastroenterology, Hepatology, and Nutrition are the Center for Liver Diseases, Inflammatory Bowel Disease Center, Pancreas and Biliary Center, Neurogastroenterology and Motility Center, Gastrointestinal Cancer Prevention and Treatment Center, Center for Intestinal Health and Nutrition Support, and the Center for Women’s Digestive Health. These centers are complemented by the clinical and procedural support of the Digestive Disorders Center and Gastrointestinal Laboratory and by collaborations with the VA Pittsburgh Healthcare System, UPMC Shadyside, and Magee-Womens Hospital of UPMC. The division’s focus on clinical and genetics research includes translational research in the following key areas: inflammatory bowel disease, pancreas and biliary system, neurogastroenterology and motility, pain, liver and transplantation medicine, colorectal cancer, and genomic sciences.

General Internal Medicine Wishwa N. Kapoor, M.D., M.P.H. Chief

Geriatric Medicine Neil M. Resnick, M.D. Chief

Inpatient clinical services in the Division of General Internal Medicine include treating all unassigned patients admitted through the emergency department, providing hospitalist care for private practices, and providing consultative services to other departments. Outpatient services are diverse and are incorporated into the Comprehensive Multidisciplinary Women’s Health Program, Primary Care Service Line and Emergent Care Center at the VA Pittsburgh Healthcare System, Shea Medical Center at UPMC Shadyside, Program for Health Care to Underserved Populations, Smoking Cessation Clinic, Pittsburgh AIDS Center for Treatment, and Comprehensive Palliative Care Program. Research is focused in two major centers: the Center for Research on Health Care and the Center for Health Equity Research and Promotion. Additional research occurs in the Section of Palliative Care and Medical Ethics, the Section of Women’s Health, and the Section of Decision Sciences and Clinical Systems Modeling. The division develops and provides leadership for the Institute for Clinical Research Education, which supports the Clinical Research Training Program, Clinician Educator Training Program, and the Clinical Scientist Training Program. The institute is devoted to the development of high quality clinical researchers throughout the schools of the health sciences.

The Division of Geriatric Medicine provides consultative and primary care for patients in all settings, including the home, office, and hospital as well as rehabilitation, assisted living, and nursing home facilities. Three major centers of ambulatory care, which are a joint venture with the Department of Psychiatry, are the Benedum Geriatric Center at UPMC Presbyterian, the Senior Care Institute at UPMC Shadyside, and Classic Care at UPMC St. Margaret. Division activities fall under the umbrella of the University of Pittsburgh Institute on Aging, which was established in 2002 to coordinate all age-related activities at the University and UPMC. The institute links UPMC’s clinical expertise in geriatrics with the University’s expertise in gerontological research and training. Research focuses on common but underinvestigated conditions, including falls, frailty, sarcopenia, osteoporosis, bladder dysfunction, chronic pain, sleep disorders, polypharmacy, and subclinical cardiovascular and peripheral vascular diseases, as well as the biology of aging. Hematology / Oncology Ronald B. Herberman, M.D. Chief

Division of Hematology/Oncology specialties include brain cancer, breast cancer, colon and gastrointestinal cancer, head and neck cancer, leukemia and lymphoma, multiple myeloma, liver cancer, lung and esophageal cancer, melanoma, oral cancer, ovarian and gynecological cancer, pediatric cancer, prostate and urological cancer, and stem cell transplantation. Facilities include a bone marrow transplant unit, hematology/ oncology outpatient clinics, and an inpatient unit. Research in the

division is translational and designed to facilitate interaction between basic researchers and clinicians. Clinical investigations take place in each of the cancer specialties. Basic research is divided into four programs: immunology, molecular and cellular oncology, molecular therapeutics and drug discovery, and molecular virology. The division maintains a broad, regional network of oncologists and hematologists who assist in conducting its numerous clinical trials. Infectious Diseases John W. Mellors, M.D. Chief

Much of the clinical activity in the Division of Infectious Diseases occurs through the provision of consult services, which are available to most of the region’s hospitals and include the Surgical Infectious Diseases Service, the Clostridium Difficile Management Team, and the Bone Marrow Transplant Infectious Diseases Service. Another clinical activity, the UPMC HIV/AIDS Program, provides care to HIV-infected persons in the tri-state area. Clinical and laboratory research is a major activity and is grouped into specific research units, including viral diseases, epidemiology, transplant infectious diseases, special pathogens, geriatric infectious diseases, surgical infections, bioterrorism, and HIV/AIDS. Pulmonary, Allergy, and Critical Care Medicine Michael P. Donahoe, M.D. Interim Chief

This division includes programs in chronic obstructive pulmonary disease research, sleep medicine, asthma, lung injury, pulmonary fibrosis, cystic fibrosis, and lung transplantation, which are organized within the framework of the Comprehensive Lung Center, a multidisciplinary initiative to provide comprehensive

care for patients with complex pulmonary diseases. The division has further enhanced the capabilities of the Pulmonary Information Management System, a digital system that provides a database of information linking clinical laboratories to hospital bedsides for patient care, teaching, and research. Research examines the pathophysiology of clinical pulmonary disease through eight core programs of research excellence: Acute Lung Injury/ Adult Respiratory Distress Syndrome, Adult Cystic Fibrosis and Host Defense, Asthma and Allergic Inflammation, Genomics in Lung Disease, Emphysema Biology and Lung Imaging, the Simmons Center for Interstitial Lung Disease, Transplantation Immunology, and Sleep Disordered Breathing and Regulation. Much of this research occurs within the Respiratory Science Center, a facility dedicated to basic and clinical research in respiratory conditions. Renal-Electrolyte Thomas R. Kleyman, M.D. Chief

The Renal-Electrolyte Division includes all aspects of general consultative nephrology, renal transplantation, peritoneal dialysis, and hemodialysis. A focal area of research is the identification and characterization of cellular processes within the kidney that are associated with normal physiology and pathophysiology. Division research also includes peritoneal dialysis infections, new methods of peritoneal dialysis, continuous renal replacement therapy, and therapeutic trials for glomerular diseases. The division oversees the Acute Renal Failure Trial Network Study, a clinical trials conglomeration with 31 study centers nationwide, including the local VA Pittsburgh Healthcare System.

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Rheumatology and Clinical Immunology Larry W. Moreland, M.D. Chief

Research in the Division of Rheumatology and Clinical Immunology is conducted through the Arthritis Institute, an interdepartmental program designed to foster integrated clinical and research activities related to arthritis, autoimmune diseases, and musculoskeletal diseases. Faculty-led research and patient care programs exist for systemic sclerosis (scleroderma), systemic lupus erythematosus, rheumatoid arthritis, polymyositis, systemic vasculitis, and osteoarthritis. The clinical component of the institute sees more than 45,000 outpatients per year and includes care for children and adults with arthritis, connective tissue diseases, and regional rheumatic disorders. Selected Research Highlights John M. Kirkwood, M.D., and

colleagues have identified protein markers in abnormal moles that can help predict whether they will progress into melanoma, the deadliest form of skin cancer. Their research found that a mole’s abnormality is positively correlated with expression of a signaling protein called STAT3 (signal transducer and activator of transcription 3), which has been linked to melanoma progression. Study participants had a history of melanoma and were treated for three months with either low- or high-dose interferon, an immune protein used to attack tumor cells. Kirkwood and his team then compared abnormal moles removed from participants immediately before and after treatment. Results indicated that high doses of interferon reduced levels of STAT3 in abnormal moles by 55 percent. In addition, levels of STAT1, an antitumor marker, increased by nearly eight times over baseline. The study demonstrated that protein marker examinations in abnormal

moles provide a useful indication of a mole’s potential malignancy and could be used to monitor interferon treatments. Mary Chester M. Wasko, M.D., M.Sc.,

and colleagues conducted a multicenter observational study of 4,905 adults with rheumatoid arthritis and found that hydroxychloroquine, a common antimalarial medication also used to treat rheumatoid arthritis and other autoimmune disorders, reduces the relative risk of developing diabetes by 77 percent. In addition, those individuals who developed diabetes were less likely to require medications to manage their disease. Even when the investigators adjusted for other risk factors like body mass index, degree of disability, and medication use, the reductions persisted. Since diabetes incidence was measured through patient self reports of diagnosis and medication use, the underlying mechanisms by which hydroxychloroquine contributes to diabetes risk reduction are not yet known. However, the results suggest that hydroxychloroquine might be appropriate as a preventive therapy for individuals with prediabetes and others at risk for the disease. Anna Lokshin, Ph.D., has identified

a series of protein markers in blood that in one study were able to diagnose ovarian cancer in 96 percent of cases. Because no single protein can be used to diagnose early-stage ovarian cancer, which is particularly difficult to detect, Lokshin examined 80 different proteins that have been associated with ovarian cancer and used a computer algorithm to analyze a series of protein markers that, in combination, could reveal the presence of the disease. In a follow-up study, Lokshin is using blood samples collected yearly from 80,000 women in a national trial. Once those results are available, she will be able to determine more clearly whether the protein panel is accurate and how early it can detect the presence of ovarian cancer.

James H. Dauber, M.D., and Naftali Kaminski, M.D., have developed a

technique that provides more definitive diagnosis for two forms of interstitial lung disease: idiopathic pulmonary fibrosis (IPF), which causes scarring of the lung tissue between the air sacs, resulting in a high death rate due to respiratory failure; and hypersensitivity pneumonitis (HP), which is prevalent in areas where people keep birds as pets and causes pneumonia-like inflammation of interstitial tissue. Traditional diagnostic techniques, including X-rays and laboratory analyses, provide similar results for IPF and HP. However, using DNA microarray, which allows analysis of thousands of genes at once, Dauber and Kaminski found that lung tissue from the two disease types differs greatly in gene expression pattern. IPF exhibits an increase in genes involved in the regrowth of lung tissue; HP shows an increase in gene expression for the inflammatory response. Therefore, although traditional therapies include antiinflammatory drugs for all patients with interstitial lung disease, the study showed that only HP should be treated with corticosteroids and other anti-inflammatory drugs; IPF would not be expected to respond to such therapies. Definitive diagnosis can help to eliminate patients’ exposure to unnecessary and potentially harmful treatments. Crohn’s disease and ulcerative colitis, both inflammatory bowel diseases, are common, chronic disorders that cause abdominal pain, diarrhea, and gastrointestinal bleeding. Richard H. Duerr, M.D., and colleagues have conducted genome-wide association studies to identify genetic factors that might contribute to these disorders. The researchers found a significant relationship between Crohn’s disease and the IL23R gene on chromosome 1p31, which encodes a receptor subunit for the proinflammatory

cytokine interleukin-23 (IL-23). An uncommon coding variant of IL23R provides strong protection against Crohn’s disease, and certain noncoding IL23R variants are associated with the disorder’s presence. Additional studies confirmed that IL23R associates with Crohn’s disease as well as with ulcerative colitis. Based on these results, Duerr and colleagues have proposed the IL-23 proinflammatory signaling pathway as a therapeutic target for inflammatory bowel disease. David C. Whitcomb, M.D., Ph.D., and

colleagues study the mutated genes underlying inherited forms of pancreatic cancer, a highly deadly disease. The researchers previously identified a susceptibility locus for familial pancreatic cancer on chromosome location 4q32-34 and conducted additional studies to identify the associated cancer gene and its function. A customized microarray of this chromosomal region revealed the greatest expression change in palladin (PALLD), a gene that encodes a cytoskeleton component controlling cell shape and motility. A mutation in a highly conserved region tracked with all affected family members and was absent in the nonaffected members. In addition, Whitcomb and colleagues observed overexpression of PALLD RNA in precancerous dysplasia and pancreatic adenocarcinoma tissue in both familial and sporadic disease. The researchers were also able to induce cytoskeletal changes, abnormal actin bundle assembly, and an increased ability to migrate in cultured cells transfected with mutant PALLD. Based on these findings, Whitcomb and colleagues concluded that abnormal PALLD causes cytoskeletal changes in pancreatic cancer and may be responsible for, or contribute to, the tumor’s strong invasive and migratory abilities.

Panic disorder and generalized anxiety disorder are prevalent in primary care, but they often go unrecognized, are associated with poor functional outcomes, and generally are ineffectively treated. Bruce L. Rollman, M.D., M.P.H., and colleagues have examined whether telephone-based collaborative care for these disorders improves outcomes for primary care patients compared to standard care where patient and physician are simply informed of the disorder. Intervention involved non-mental health professionals who provided patients with psychoeducation, assessed preferences for guideline-based care, monitored treatment responses, and informed physicians of their patients’ care preferences and progress. The researchers assessed patients for anxiety and depressive symptoms, mental health-related quality of life, and employment status at baseline and two, four, eight, and 12 months after the primary care contact. At 12 months, intervention patients reported reduced anxiety and depressive symptoms; improved mental health-related quality of life; and improvements relative to baseline in hours worked per week and work days absent. Rollman and colleagues concluded that telephonebased collaborative care for panic disorder and generalized anxiety disorder is more effective than standard care in improving anxiety symptoms, health-related quality of life, and work-related outcomes. Alfred L. Fisher, M.D., Ph.D., and

colleagues study the Caenorhabditis elegans orphan nuclear hormone receptor gene daf-12, which plays a key role in developmental regulation and determination of adult longevity. The researchers have examined the effects of daf-12 on aging by characterizing the lifespan of lossof-function and gain-of-function daf-12 alleles. Fisher and colleagues determined that these mutations have opposing effects on longevity and resistance to oxidative and

thermal stress, thus making daf-12 the first gene with alleles found to extend or shorten lifespan. Fisher and colleagues determined that the loss-of-function mutation’s shortened lifespan is due to accelerated aging in young adulthood rather than an adverse effect on development. Microarray analysis of worms carrying the two alleles revealed that while the genetic profiles of the two alleles are largely different, there is significant overlap among the genes downregulated, but not upregulated, in all profiles. Fisher and colleagues concluded that daf-12 modulates aging and stress responses, in part, through the repression of specific genes. Anuradha Ray, Ph.D., and colleagues have examined whether different types of dendritic cells (DCs) initiate different immune outcomes, like tolerance or inflammation. The researchers characterized DCs from the lung-draining lymph nodes of mice immunized for allergic airway inflammation or tolerance and examined their interactions with CD4+ T cells. The DC population derived from tolerized mice resembled plasmacytoid-type DCs and were poor inducers of T-cell proliferation. However, DCs from the inflammatory condition resembled myeloid-type DCs. In both conditions, DCs induced interleukin-4 (IL-4) production, but the T cells cultured with tolerogenic DCs were unresponsive to IL-4. These data suggest that DC phenotype in lung-draining lymph nodes determines whether an airway will experience tolerance or inflammation.

Primary biliary cirrhosis (PBC), which carries a strong genetic component, is an autoimmune disease characterized by biliary ductular inflammation with eventual liver cirrhosis. William M. Ridgway, M.D., and colleagues have demonstrated that nonobese diabetic (NOD).c3c4 mice develop an autoimmune biliary disease (ABD) that models human

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PBC. The serologic hallmark of PBC is antimitochondrial antibodies that react with the pyruvate dehydrogenase complex, targeting the inner lipoyl domain of the E2 subunit (antiPDC-E2). NOD.c3c4 mice develop antibodies to PDC-E2 that are specific for the inner lipoyl domain. Affected areas of biliary epithelium are infiltrated with CD3+, CD4+, and CD8+ T cells, and treatment of NOD.c3c4 mice with monoclonal antibody to CD3 protects from ABD. Furthermore, NOD.c3c4-scid (severe combined immunodeficient) mice develop disease after adoptive transfer of CD4+ T cells, demonstrating a central role for T cells in pathogenesis. Using a gene-mapping approach, Ridgway and colleagues defined the first ABD locus, Abd1. These results establish the NOD.c3c4 mouse as the first spontaneous mouse model of PBC.

Centers Arthritis Institute Thomas A. Medsger Jr., M.D. Director Asthma, Allergy, and Airway Research Center Sally Wenzel, M.D. Director Cardiovascular Institute Barry London, M.D., Ph.D. Director Center for Clinical Pharmacology Robert A. Branch, M.D. Director Center for Health Equity Research and Promotion Michael J. Fine, M.D., M.Sc. Director Center for Liver Diseases Obaid Shakil Shaikh, M.B.B.S. Director

Sharon A. Riddler, M.D., M.P.H., and

colleagues have conducted a clinical trial to evaluate the efficacy of two commonly used HIV treatments. The researchers found that a tripledrug approach using two nucleoside reverse transcriptase inhibitors (NRTIs) plus efavirenz, a nonnucleoside reverse transcriptase inhibitor (NNRTI), suppressed the virus to undetectable levels in more individuals than the other tripledrug combination of two NRTIs and a protease inhibitor (lopinavir/ ritonavir). Riddler and colleagues also found that a two-drug treatment regimen combining efavirenz with lopinavir/ritonavir (NRTI-sparing approach) performed nearly as well as the efavirenz plus NRTI combination and eliminated the side effects often produced by NRTI-based therapy. Additional analyses revealed that while treatment with lopinavir/ ritonavir plus NRTI produced a greater CD4+ T cell count, both regimens using efavirenz experienced less virologic failure, or rebound, of the HIV virus.

Center for Research on Health Care Wishwa N. Kapoor, M.D., M.P.H. Director Comprehensive Lung Center Christopher N. Faber, M.D. Director Data Center Doris M. Rubio, Ph.D. Director Digestive Disorder Center Barry Kisloff, M.D. Director Gastrointestinal Cancer Prevention and Treatment Center Robert E. Schoen, M.D., M.P.H. Director General Infectious Diseases Clinical Program Karin E. Byers, M.D. Director HIV/AIDS Clinical Research Program Deborah D. McMahon, M.D. Director

Inflammatory Bowel Disease Center Richard H. Duerr, M.D. Miguel D. Regueiro, M.D. Co-directors

Regular Faculty

Institute for Clinical Research Education Wishwa N. Kapoor, M.D., M.P.H. Director

D. A. Henderson, M.D., M.P.H. 21st Century Professor of Medicine and Public Health

Institute for Doctor–Patient Communication Robert M. Arnold, M.D. Director Institute to Enhance Palliative Care David Barnard, Ph.D. Director LHAS Women’s Heart Center Steven E. Reis, M.D. Director Neurogastroenterology and Motility Center Klaus Bielefeldt, M.D., Ph.D. Director Obesity / Nutrition Research Center Bret H. Goodpaster, Ph.D. John Jakicic, Ph.D. (Department of Health and Physical Activity, School of Education) Co-directors Osteoporosis Prevention and Treatment Center Susan L. Greenspan, M.D. Director Pancreas and Biliary Center David C. Whitcomb, M.D., Ph.D. Director Simmons Center for Interstitial Lung Disease Naftali Kaminski, M.D. Director University of Pittsburgh Institute on Aging Neil M. Resnick, M.D. Director

Endowed Chairs Robert M. Arnold, M.D. Dr. Leo H. Criep Professor of Patient Care

Ronald B. Herberman, M.D. Hillman Professor of Oncology Wishwa N. Kapoor, M.D., M.P.H. Falk Professor of Ambulatory Care Frank J. Kroboth, M.D. George H. Taber Professor of General Internal Medicine Barry London, M.D., Ph.D. Harry S. Tack Professor Thomas A. Medsger Jr., M.D. Dr. Gerald P. Rodnan Professor of Rheumatology Steven D. Shapiro, M.D. Dr. Jack D. Myers Professor and Chair David C. Whitcomb, M.D., Ph.D. Giant Eagle Foundation Professor of Cancer Genetics Lawrence Ellis Chair in Hematology and Oncology (open) Margaret Jane Miller Chair in Arthritis Research (open) James A. Shaver Chair in Cardiovascular Education (open) Dorothy P. and Richard P. Simmons Chair in Pulmonary Research (open) Sandra and Thomas Usher Chair in Melanoma (open)

Professors Janet A. Amico, M.D. Morteza Amidi, M.D. Gerard L. Apodaca, Ph.D. David Barnard, Ph.D. Robert A. Branch, M.D. Preet M. Chaudhary, M.B.B.S., Ph.D. Frederick R. DeRubertis, M.D. Albert D. Donnenberg, Ph.D. Merrill J. Egorin, M.D. Lawrence D. Ellis, M.D. D. Michael Elnicki, M.D. Michael J. Fine, M.D., M.Sc. William P. Follansbee, M.D. Kenneth A. Foon, M.D. John Gorcsan III, M.D. Rosanne Granieri, M.D. Susan L. Greenspan, M.D. Lee H. Harrison, M.D. Elmer J. Holzinger, M.D. Susan C. Hunt, M.D. Rajiv Jain, M.B.B.S. John P. Johnson, M.D. James R. Johnston, M.D. John M. Kirkwood, M.D. Thomas R. Kleyman, M.D. Mary T. Korytkowski, M.D. C. Kent Kwoh, M.D. Arthur S. Levine, M.D. David S. Macpherson, M.D. Kenneth S. McCarty Jr., M.D., Ph.D. Jerry McCauley, M.D. Melissa A. McNeil, M.D. John W. Mellors, M.D. Robert R. Muder, M.D. Tara J. O’Toole, M.D. Chester V. Oddis, M.D. Thomas D. Painter, M.D. Paul M. Palevsky, M.D. Rosa Lynn B. Pinkus, Ph.D. Beth M. Piraino, M.D. Margaret V. Ragni, M.D. R. Harsha Rao, M.D. Anuradha Ray, Ph.D. P. Sudhakar Reddy, M.D. Steven E. Reis, M.D. Neil M. Resnick, M.D. Mark S. Roberts, M.D., M.P.P. Robert M. Rogers, M.D. Garson David Roodman, M.D., Ph.D. Fred H. Rubin, M.D. Mark H. Sanders, M.D. Robert E. Schoen, M.D., M.P.H. James A. Shaver, M.D. Adam Slivka, M.D., Ph.D. Thomas C. Smitherman, M.D. Andrew F. Stewart, M.D. Stephanie Anne Studenski, M.D.

Mark E. Thompson, M.D. Philip Troen, M.D. Victor Vogel III, M.D. Victor L. Yu, M.D. Visiting Professors Joseph T. Hanlon, Pharm.D., M.D. Frederick London Moolten, M.D. Larry W. Moreland, M.D. Stephen J. O’Keefe, M.D. Roy E. Smith, M.D. Sally Wenzel, M.D. Associate Professors Joseph M. Ahearn, M.D. Kathryn M. Albers, Ph.D. Athanassios Argiris, M.D. Charles W. Atwood Jr., M.D. William W. Barrington, M.D. Anthony J. Bauer, Ph.D. Klaus Bielefeldt, M.D., Ph.D. Lori Ann Birder, Ph.D. Franklin A. Bontempo, M.D. James Edward Bost, Ph.D. Robert C. Brooks, M.D., Ph.D. Adam M. Brufsky, M.D., Ph.D. Angel Lopez Candales, M.D. Timothy M. Carlos, M.D. Gurkamal Singh Chatta, M.B.B.S. Mary E. Choi, M.D. Peter J. Counihan, M.B.B.Ch. Brian Mark Davis, Ph.D. Bruce W. Dixon, M.D. Michael P. Donahoe, M.D. Richard H. Duerr, M.D. Steven R. Duncan, M.D. Patricia K. Eagon, Ph.D. Daniel Edmundowicz, M.D. Christopher N. Faber, M.D. Gary S. Fischer, M.D. Linda F. Fried, M.D. Adolfo García-Ocaña, Ph.D. Kevin F. Gibson, M.D. Chester B. Good, M.D. Emily E. Grum, M.D. Joan Harvey, M.D. Peggy B. Hasley, M.D. Robert M. Hoffman, M.D. Rebecca P. Hughey, Ph.D. Said A. Ibrahim, M.D. Thomas Vincent Inglesby Jr., M.D. Daniel E. Johnson, Ph.D. Naftali Kaminski, M.D. Steven L. Kanter, M.D. William E. Katz, M.D. Joseph E. Kiss, M.D. Kevin L. Kraemer, M.D. John W. Kreit, M.D.

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Jenifer E. Lee, M.D. Joon S. Lee, M.D. Barbara Edith Ley, M.D. Anna Lokshin, Ph.D. Susan M. Manzi, M.D. Markus Y. Mapara, M.D. James Barry McGee, M.D. Deborah D. McMahon, M.D. Dennis M. McNamara, M.D. Matthew F. Muldoon, M.D. Robert M. O’Doherty, Ph.D. Christopher P. O’Donnell, Ph.D. Elizabeth A. O’Keefe, M.B.B.Ch. David L. Paterson, M.D. Joseph M. Pilewski, M.D. Mordechai Rabinovitz, M.D. Prabir Ray, Ph.D. Robert L. Redner, M.D. Miguel D. Regueiro, M.D. Sharon A. Riddler, M.D., M.P.H. Michelle M. Roberts, M.D. Eric G. Rodriguez, M.D. Bruce L. Rollman, M.D., M.P.H. Doris M. Rubio, Ph.D. David S. Schwartzman, M.D. Frank C. Sciurba, M.D. Obaid Shakil Shaikh, M.B.B.S. Linda M. Siminerio, Ph.D. Nina Singh, M.D. Anson J. Smith, M.D. Richard A. Steinman, M.D., Ph.D. Patrick J. Strollo, M.D. Galen E. Switzer, Ph.D. Gary H. Tabas, M.D. Adele L. Towers, M.D. Flordeliza S. Villanueva, M.D. Molly T. Vogt, Ph.D. Mary Chester M. Wasko, M.D., M.Sc. Debra K. Weiner, M.D. Ora A. Weisz, Ph.D. Visiting Associate Professors Rene J. Alvarez, M.D., Ph.D. Filitsa H. Bender, M.D. Kapil Brijmohan Chopra, M.B.B.S. Michael S. Gold, Ph.D. Penny J. Hitchcock, D.V.M. Kaikobad J. Irani, M.D. Noriyoshi Kurihara, D.D.S., Ph.D. William I. Levin, M.D. Monica C. Panelli, Ph.D. Kanchan H. Rao, M.B.B.S. Marjorie Romkes, Ph.D. Werner Schaefer, D.I. Donald Kenneth Scott, Ph.D. Mary Ann Sevick, Sc.D.

Research Associate Professors Raghvendra K. Dubey, Ph.D. Charles F. McTiernan, Ph.D. Zeynep Ozlem Soran, M.D. Yingze Zhang, Ph.D. Visiting Research Associate Professors Xucai Chen, Ph.D. James P. DeLany, Ph.D. Petr Pancoska, Ph.D. Vladimir Borisovich Ritov, Ph.D. Assistant Professors Ume Lubna Abbas, M.B.B.S. Steven R. Abo, M.D. Ferhaan Ahmad, M.D., Ph.D. Jawad Ahmad, M.D. William D. Anderson, M.D. Eric J. Anish, M.D. Leonard J. Appleman, M.D., Ph.D. Dana P. Ascherman, M.D. Nathan Bahary, M.D., Ph.D. Leonard Kweku Baidoo, M.D. Amber Elizabeth Barnato, M.D. Raveen Raj Bazaz, M.B.B.S. Jaideep Behari, M.B.B.S., Ph.D. Roberto Pablo Benzo, M.D. Jose Francisco Bernardo, M.D. Lori Marie Bigi, M.D. Sandra A. Blakowski, M.D. Luciana Lopes Borio, M.D. Carol Feghali Bostwick, Ph.D. Michael Boyiadzis, M.D. Anthony G. Brickner, Ph.D. Lawrence A. Bucklew Jr., M.D. Diemthuy D. Bui, M.D. Peter D. Bulova, M.D. Gregory Matthew Bump, M.D. Raquel A. Buranosky, M.D., M.P.H. Timothy Ray Burke, M.D. Adeel Ajwad Butt, M.B.B.S. Lisa H. Butterfield, Ph.D. Karin E. Byers, M.D. Linda M. Cadaret, M.D. Geetha Chalasani, M.B.B.S. Sue M. Challinor, M.D. Melissa Clark, M.D. Jeffrey S. Cohen, M.D. Brenda Sue Cole, Ph.D. Nancy Camp Scherer Connolly, M.D. Margaret Baldwin Conroy, M.D., M.P.H. Amanda Leigh Cooper, M.D. Maria Mercedes Crespo, M.D. Fred William Crock, M.D. Megan S. Cunnane, M.D. Qianyu Dang, Ph.D. Hollis D. Day, M.D. Robert S. Edinger, Ph.D. Alfred L. Fisher, M.D., Ph.D. Janine Michelle Frank, M.D. Matthew S. Freiberg, M.D.

Elodie Ghedin, Ph.D. Alison Morris Gimbel, M.D. Rachel J. Givelber, M.D. Alda Maria R. Gonzaga, M.D. Bret H. Goodpaster, Ph.D. Adam J. Gordon, M.D. Gigi Kwik Gronvall, Ph.D. Vijay Kumar Gulati, M.D. Kenneth Raymond Hallows, M.D., Ph.D. Steven M. Handler, M.D. Susan Elizabeth Hardy, M.D., Ph.D. Shuja Hassan, M.B.B.S. Randy S. Hebert, M.D., M.P.H. Refaat Mohamed Hegazi, M.B.Ch.B., Ph.D. Rachel Hess, M.D. Kevin Ho, M.D. Erika L. Hoffman, M.D. Ashley M. Houghton II, M.D. Shahid Husain, M.B.B.S. Emily J. Jaffe, M.D. Sandeep K. Jain, M.D. Harish Jasti, M.D., M.Sc. Yang Jin, M.D. Bruce A. Johnson, M.D. Anthony J. Kanai, Ph.D. Hossam E. Kandil, M.B.Ch.B., Ph.D. Amy Hui-Chien Kao, M.D. Asif Khalid, M.B.B.S. Linda A. King, M.D. Barry Kisloff, M.D. Russell C. Kolarik, M.D. Eswar Krishnan, M.B.B.S. Haruko Kuffner, M.D. Janet Harrison Kuzmishin, M.D. Eun Jeong Kwak, M.D.C.M. Phillip E. Lamberty, M.D. Steven S. Lasky, M.D. Laurie L. Lavery, M.D. Jonathan J. Lebowitz, M.D. Ashley Lee, M.D. Bruce Yung Lee, M.D. Byeong-Chel Lee, Ph.D. Janet Sojung Lee, M.D. Suzanne Lentzsch, M.D. Bruce S. Ling, M.D., M.P.H. Cynthia E. Luck, D.O. Oscar C. Marroquin, M.D. Michael Mathier, M.D. Megan Crowley Matoka, Ph.D. David J. McAdams, M.D. Kenneth R. McGaffin, M.D., Ph.D. Kevin M. McGrath, M.D. John Ernest McKinnon, M.D. Kathleen Maksimowicz McKinnon, D.O. Kathleen Mary McTigue, M.D. Bryan J. McVerry, M.D. Derek Clark Molliver, Ph.D.

Keith Howard Morgenlander, M.P.H. Natalia Emily Morone, M.D. E. Danielle Dyck Morse, M.D. Stergios Moschos, M.D. Visala S. Muluk, M.B.B.S. Suresh R. Mulukutla, M.D. Carlene Muto, M.D. Larissa Myaskovsky, Ph.D. David A. Nace, M.D. Smita Nayak, M.D. Jan Nemec, M.D. Ogundu C. Obioha Ngwu, M.D. Mark H. Overton, M.D. John J. Pacella, M.D. Georgios Ioannis Papachristou, M.D. Nuria Maria Pastor-Soler, M.D., Ph.D. K.P.G. Subashan Perera, Ph.D. Andrej Aleksandar Petrov, M.D. Michael A. Pezzone, M.D., Ph.D. Louis A. Piccoli, M.D. Eva Pizzoferrato, Ph.D. Donna M. Posluszny, Ph.D. Ruth M. Preisner, M.D. Brian Adam Primack, M.D. Suresh Sakkarai Ramalingam, M.B.B.S. Ravi Neelakanian Ramani, M.D. Makum L. Ramesh, M.D. Sangeeta Rana, M.D., M.P.H. Priya Rastogi, M.D. William M. Ridgway, M.D. Mara Horwitz Rodosky, M.D. Keri Lyn Rodriguez, Ph.D. Ivan Rosas, M.D. Michelle I. Rossi, M.D. Samir Saba, M.D. Roseann J. Salata, M.D. Michael K. Sanders, M.D. John T. Schindler, M.D. Mark Schmidhofer, M.D. Monica Lynn Schoch-Spana, Ph.D. Eleanor Bimla Bachrach Schwarz, M.D. Jigme M. Sethi, M.B.B.S. Nirav Arvind Shah, M.D. Alaaeldin A. Shalaby, M.B.B.Ch. Vladimir Shusterman, M.D., Ph.D. Marc Alan Simon, M.D. Nicolas Paul Sluis-Cremer, Ph.D. Bradley T. Smith, Ph.D. Kenneth J. Smith, M.D. Prem Soman, M.B.B.S. Ali Fuat Sonel, M.D. Carla L. Spagnoletti, M.D. Sean Michael Studer, M.D. Kathleen Leone Sward, Ph.D. Nathalie Madeleine Taesch, Ph.D. Ahmad Ali Tarhini, M.D. Jeffrey J. Teuteberg, M.D.

Winifred Gresens Teuteberg, M.D. Hilary A. Tindle, M.D., M.P.H. Stevan P. Tofovic, M.D., Ph.D. Asher Tulsky, M.D. Mark L. Unruh, M.D. Rupangi Vasavada, Ph.D. Peter J. Veldkamp, M.D. Emanuel N. Vergis, M.D. Steven D. Weisbord, M.D. David O. Wilson, M.D. Rollin M. Wright, M.D. Christine Mona Wu, M.D. Guozhi Xiao, M.D., Ph.D. Dhiraj Yadav, M.B.B.S. Dianne Marie Zalenski, M.D. Hassane Zarour, M.D. Susan Lynn Zickmund, Ph.D. Visiting Assistant Professors Evan C. Adelstein, M.D. Aryan Narayan Aiyer, M.D. Sonya B. Borrero, M.D. Yvonne Ruoh Lei Chan, M.D. Anthony Benjamin Csoka, Ph.D. Beth A. Fischer, Ph.D., M.Ed. Aneal Sitaram Gadgil, M.B.B.S. Michael Kevin Gibson, M.D. Fotios Koumpouras, M.D. Yan Lin, Ph.D. Subhendra Mattagajasingh, Ph.D. Ateev Mehrotra, M.D. Michael M. Myerburg, M.D. Navin Rajagopalan, M.D. Sun Kim Scolieri, M.D. Catalin Toma, M.D. Andrew H. Voigt, M.D. Jian Zhang, M.D., Ph.D. Research Assistant Professors Meenakshi Arora, Ph.D. Silvana Balzar, M.D. Teresa A. Brosenitsch, Ph.D. Cindy L. Bryce, Ph.D. Marcelo Daniel Carattino, Ph.D. Chung-Chou Ho Chang, Ph.D. Timothy E. Corcoran, Ph.D. Deborah Lynn Galson, Ph.D. Aurelio D. Gomes, M.D. Julia Butler Greer, M.D. Elias K. Halvas, Ph.D. Sung Il Kim, Ph.D. Chau-Ching Liu, M.D., Ph.D. Jane Whitman Marsh, Ph.D. Hittu Matta, Ph.D. Haider Mehdi, Ph.D. Gunhild M. Mueller, Ph.D. Elizabeth Ann Mundy, Ph.D. Timothy B. Oriss, Ph.D. Veronica Garcia Palacios, Ph.D. Vasu Punj, Ph.D. Zengbiao Qi, Ph.D.

Thomas J. Richards, Ph.D. Stefan W. Ryter, Ph.D. Shaohu Sheng, M.D. Heena S. Sheth, M.D. Qingde Wang, M.D., Ph.D. Wenjun Wang, M.D., Ph.D. Kelly Maureen Weixel, Ph.D. Wei Wu, Ph.D. Hui Xu, M.D., Ph.D. Xui Xia Zhou, Ph.D. Xiaodong Zhu, Ph.D. Visiting Research Assistant Professors Uddhav Prabhakar Kelavkar, Ph.D. Faina Linkov, Ph.D. Instructors Amelia G. Bartels, M.D. Susan E. Brode, M.D. Irene Cozar, Ph.D. Frederico Granchi De Toledo, M.D. Robyn Theresa Domsic, M.D. Jennifer Rae Elliott, M.D. Ji-Yang Lee, M.D. Majd Mouded, M.D. Chenits Pettigrew Jr., Ph.D. Fernanda Pinho Silveira, M.D. Maja Stefanovic-Racic, M.D., Ph.D. Darcy L. Thull, M.S. Visiting Instructors Rachel A. Bonnema, M.D. Kenneth Edward Fasanella, M.D. Scott R. Herrle, M.D. Caroline Yen-Hsueh Lin, M.D. Christopher J. Passero, M.D. Research Instructors Laura Cristina Alonso, M.D. Anna Blumental-Perry, Ph.D. Shama C. Buch, Ph.D. Chang Sook Hong, Ph.D. Bo Hu, Ph.D. Ossama B. Kashlan, Ph.D. Michelle Miranda, Ph.D. Ruth A. Modzelewski, Ph.D. Nicolas André Stirling Stewart, Ph.D. Nathalie Khoueiry Zgheib, M.D.

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MOLECULAR

GENETICS

AND

BIOCHEMISTRY

DEPARTMENTS

Joseph C. Glorioso III, Ph.D., Dr. William S. McEllroy Professor and Chair

DEPARTMENT PROFILE

The Department of Molecular Genetics and Biochemistry is a national leader in infectious disease, biochemistry of signaling and DNA repair, developmental biology, and molecular medicine research. Department scientists play a key role in developing initiatives in animal modeling of human diseases, novel approaches to vaccine development and drug discovery, and the understanding of infectious agents’ molecular mechanisms of action. The department contributes to training grants in gene therapy, neuroscience, immunology, virology, and biotechnology. In addition to extensive federally funded research, faculty members are also engaged in entrepreneurial ventures involving research alliances with industry.

Graduate Training

The Interdisciplinary Biomedical Graduate Program combines a vigorous academic environment with modern biomedical research. Ph.D. students take interdisciplinary core courses during the first year and then focus on a particular area of biomedical research for the remainder of their degree program. Faculty members provide expertise in both basic and clinical research; and collaborative efforts between basic and clinical investigators establish a translational research environment, facilitating the transfer of knowledge from bench to bedside. Selected Research Highlights

expression data from the DNA repairdeficient mice indicate increased cell death and antioxidant defenses; a shift toward anabolism; and reduced growth hormone/insulin-like growth factor 1 (IGF1) signaling, a known lifespan regulator. Similar changes are seen in wild-type mice chronically exposed to DNA damaging agents or that are calorically restricted or aged. Niedernhofer and colleagues conclude that stress, including DNA damage, induces a metabolic response mediated by the IGF1/insulin pathway that reallocates cellular resources toward maintenance rather than proliferation and helps preserve life. The data also demonstrate that DNA damage promotes rapid aging.

Laura J. Niedernhofer, M.D., Ph.D.,

and colleagues are studying the health effects of DNA damage. The research team engineered mice defective in a DNA repair gene called Ercc1 and discovered a severe and spontaneous phenotype of accelerated aging and shortened lifespan. Using this model, Niedernhofer and colleagues demonstrated that ERCC1XPF endonuclease is required for repair of DNA interstrand crosslinks, a particular type of DNA damage that renders the two strands of a DNA helix inseparable and, therefore, unable to produce proteins or to be copied; it also is required for repair of DNA double-strand breaks. Both types of lesions are exquisitely cytotoxic, killing cells if not repaired. Gene

Fibroblast growth factors (FGFs) are secreted molecules that activate signaling pathways required for proper embryogenesis. Using gene expression (in situ hybridization) screening studies in zebrafish, Michael Tsang, Ph.D., and his laboratory have identified a group of genes that exhibit expression patterns similar to those of FGF genes. The researchers have characterized the zebrafish protein MAP kinase phosphatase 3 (MKP3), a member of the FGF synexpression group, and shown that it has a crucial role in the specification of axial polarity in the early zebrafish embryo. MKP3 dephosphorylates the activated form of MAP kinase (MAPK), inhibiting the Ras/MAPK arm of the FGF signaling pathway. Gain- and

loss-of-function studies reveal that MKP3 is required to limit the extent of FGF/Ras/MAPK signaling in the early embryo. Disturbing this inhibitory pathway disrupts dorsoventral patterning at the onset of gastrulation. Tsang and colleagues have now established transgenic zebrafish that report on FGF signaling in live embryos. This achievement was made by the generation of green fluorescent reporter lines that are controlled by active FGF signaling. These fish can act as biosensors for FGF activity and allow the possibility to rapidly screen chemical libraries for novel compounds that modulate the FGF pathway. The goal is to identify chemical probes to investigate the role of FGFs in development, and these small molecules can potentially be developed into novel therapeutics in the treatment of FGF-related disorders. Stefan M. Duensing, M.D., and

colleagues have determined that transient, low intensity replication stress leads to rapid activation of the DNA replication checkpoint and a significantly delayed apoptotic response in a small but significant number of cells. This delayed apoptotic response was independent of the p53 transcription factor, and the researchers found evidence of cell death during mitosis. Duensing and colleagues analyzed mouse embryonic fibroblasts (MEFs) deficient in p53 and compared them to wild-type as well as p63- or p73-deficient MEFs. P53-deficient MEFs alone showed a significant increase in apoptosis and signs of failed mitosis, like multinucleation, following replication stress. Multinucleated p53-deficient MEFs frequently retained cyclin B1 expression, indicating a persistently activated mitotic spindle checkpoint (MSC). The researchers’ results suggest that the cellular response to replication stress often involves MSC

and implies that MSC may act in concert with DNA damage and cell cycle checkpoints as an early antitumor barrier. Borrelia burgdorferi, the spirochete responsible for Lyme disease, is spread by the bite of an infected Ixodes tick. James A. Carroll, Ph.D., has used a multiple two-dimensional gel technique combined with proteomics to show the full humoral immune response of mice and Lyme patients to membrane-associated proteins isolated from B. burgdorferi. A subset of immunogenic membraneassociated proteins was recognized by mice experimentally infected with B. burgdorferi, but most of the proteins were recognized by sera from patients diagnosed with early disseminated Lyme disease. By examining the humoral response in Lyme patients over time, Carroll identified the sequence of immunoreactive proteins as the disease progresses from early to late stages. This serologic proteome analysis enabled the identification of novel membraneassociated proteins that may serve as new diagnostic markers and, more importantly, as second-generation vaccine candidates for protection against Lyme disease. Paul D. Robbins, Ph.D., and colleagues

have successfully prevented hyperglycemia (elevated blood sugar) in diabetes-prone mice using state-ofthe-art gene therapy techniques. Using an adeno-associated virus gene delivery system, the investigators inserted genes encoding for the cytokine interleukin-4 (IL-4) or IL-10 into insulin-producing beta cells, called islet cells, of non-obese diabetic (NOD) mice. IL-4 expression prevented hyperglycemia, whereas IL-10 expression accelerated the increase in blood sugar. Robbins and colleagues also demonstrated that transplantation of the IL-4 transduced islet cells not only restored normal

glucose responsiveness in NOD mice but did not elicit an immune response. These results demonstrate that adeno-associated viral vectors are an effective tool for islet-based gene transfer and transplantation. Francisella tularensis, the causative agent of tularemia and a Category A biodefense agent, replicates within host macrophages, though its pathogenesis is poorly understood. Gerard J. Nau, M.D., Ph.D., and colleagues have isolated a variant of F. tularensis live vaccine strain (LVS) based on colony morphology and effect on macrophages. Human monocyte-derived macrophages produced more tumor necrosis factor alpha, interleukin (IL)-1beta, IL-6, and IL-12 p40 following exposure to the variant, designated as the activating variant (ACV). Although LVS and ACV lipopolysaccharide immunoreactivity was comparable to that described in a previous variant, the researchers showed that soluble protein fractions of LVS and ACV differed. Further investigation using two-dimensional gel electrophoresis demonstrated differential protein expression, featuring several proteins associated with virulence in F. tularensis and other pathogens. In addition, after growth in a chemically defined medium, ACV reverted to the LVS phenotype. These data show that virulence factor levels in F. tularensis are modulated by culture conditions and that this modulation affects host responses.

Regular Faculty Endowed Chair Joseph C. Glorioso III, Ph.D. Dr. William S. McEllroy Professor and Chair Distinguished Service Professor Emeritus Julius S. Youngner, Sc.D. Professors Michael M. Corb, Ph.D. Neal A. DeLuca, Ph.D. Joanne L. Flynn, Ph.D. Saleem A. Khan, Ph.D. Bruce A. McClane, Ph.D. Ronald C. Montelaro, Ph.D. Patrick S. Moore, M.D., M.P.H. Sidney M. Morris, Ph.D. Michael A. Parniak, Ph.D. Paul D. Robbins, Ph.D. Thomas E. Smithgall, Ph.D. Associate Professors Michael Cascio, Ph.D. J. Richard Chaillet, M.D., Ph.D. Fred L. Homa, Ph.D. Timothy A. Mietzner, Ph.D. Baskaran Rajasekaran, Ph.D. Martin C. Schmidt, Ph.D. Visiting Associate Professor Gutian Xiao, Ph.D. Research Associate Professors Patricia W. Dowling, Ph.D. Jaspal S. Khillan, Ph.D. Assistant Professors James A. Carroll, Ph.D. Stefan M. Duensing, M.D. Ole Victor Foenss Gjoerup, Ph.D. Neil A. Hukriede, Ph.D. Hiroyuki Nakai, M.D., Ph.D. Gerard J. Nau, M.D., Ph.D. Laura J. Niedernhofer, M.D., Ph.D. Ted M. Ross, Ph.D. Michael Tsang, Ph.D. Research Assistant Professors William F. Goins, Ph.D. James R. Goss, Ph.D. Mofazzal Hossain, Ph.D. Malcom Meyn III, Ph.D. Vesna Rapic-Otrin, Ph.D. Jodi Kristine Craigo Steckbeck, Ph.D. Research Instructor Justus B. Cohen, Ph.D.

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NEUROBIOLOGY

DEPARTMENTS

Susan G. Amara, Ph.D., Dr. Thomas Detre Professor of Neuroscience and Chair

DEPARTMENT PROFILE

Gonzalo E. Torres, Ph.D., and

The Department of Neurobiology has established strengths in neural development; circuit and systems function; cellular communication through receptors, channels, and synapses; and neurological and psychiatric diseases. Research in these areas is integrated with work being done in other departments of the School of the Medicine (Psychiatry, Pharmacology, and Neurology), the School of Engineering, and the School of Arts and Sciences. In addition, department faculty members are involved in research and training activities of the crosscampus Center for Neuroscience as well as the Center for the Neural Basis of Cognition, a joint program with Carnegie Mellon University.

colleagues have studied early-onset torsion dystonia (EOTD), an autosomal dominant movement disorder characterized by involuntary and sustained muscle contractions that often result in severe disability. EOTD is usually caused by deletion of one glutamic acid in the carboxyl terminus of the protein torsinA, resulting in protein aggregation in perinuclear inclusions. The investigators have shown that torsinA regulates cellular trafficking of the dopamine transporter, as well as other polytopic membrane-bound proteins, and that this effect can be prevented by mutating the torsinA adenosine triphosphate (ATP) binding site. The dystonia-associated torsinA deletion mutant (DeltaE-torsinA) did not affect the cell surface distribution of polytopic membrane-associated proteins, suggesting that the EOTDlinked mutation produces a loss of function. However, a mutation in the ATP binding site in DeltaE-torsinA reversed the mutant’s aggregate phenotype and produced a dominant negative of wild-type torsinA. These results provide evidence for a functional role for torsinA and a loss of function and a dominant-negative phenotype of the DeltaE-torsinA mutation that may contribute to the autosomal dominant nature of the condition.

Graduate Training

Selected Research Highlights

The establishment of the Center for Neuroscience at the University of Pittsburgh in 1984 provided a Ph.D. training program involving faculty and students from both the School of Medicine and the School of Arts and Sciences. The program offers extensive exposure to research and promotes collaboration through the example and direction of its faculty. With its diversity and flexibility of research, the program provides the opportunity for broad educational experiences in all aspects of the discipline, including the molecular basis of cellular communication, psychiatric and neurological disorders, neural systems and information processing in brain circuits, neural development and cellular growth, cognitive neuroscience, and homeostatic regulatory systems.

Ole V. Mortensen, Ph.D., and Susan G. Amara, Ph.D., have determined that two atypical dopamine transporter (DAT) inhibitors, benztropine and bupropion, show greatly different psychostimulant effects than another DAT inhibitor, cocaine. Because benztropine has been suggested as a target for drug development against cocaine abuse, the investigators wanted to characterize this difference. Despite a high degree of sequence similarity, DATs and norepinephrine transporters (NETs) express distinctive pharmacology, including the DATs’ higher sensitivity to benztropine and bupropion. Mortensen and Amara used site-directed mutagenesis to produce NET mutants as a means to isolate the DAT sequences responsible for the differential sensitivity. The investigators demonstrated that incorporating alanine 279 in transmembrane domain 5 (TM5) and serine 359 in TM7 increased the NETs’ sensitivity to bupropion and benztropine. The results identify residues that are important for the unique molecular interactions of benztropine and bupropion with DATs and may contribute to the distinct behavioral actions of these drugs.

The peripheral regeneration of sensory neurons following nerve transection often results in the misalignment of previously precise connections between primary sensory neurons and cells in the spinal cord, resulting in a loss of tactile acuity. H. Richard Koerber, Ph.D., studies specific changes in the organization of the spinal cord’s dorsal horn that result from reinnervation following transection. These changes may

contribute to the rate of recovery for tactile acuity, as measured by twopoint discrimination, and the possible onset of chronic pain. Koerber’s laboratory has shown that synapse efficacy between regenerated sensory neurons and the dorsal horn may be altered dramatically and seems to result from both a loss of input and the establishment of new connections. These alterations influence the dorsal horn’s somatotopy as it recovers, and behavioral studies have shown that the dorsal horn’s reorganization pattern correlates well with the recovery of two-point discrimination thresholds. The Koerber lab is also investigating a novel class of nociceptive connections that are formed during reinnervation of the dorsal horn. Guo-Qiang Bi, Ph.D., examines

population activity in networks of cultured neurons as a model of neuronal circuit development in the brain. This activity, or reverberation, is reminiscent of Hebbian dynamics, by which neuronal activity causes increased synaptic strength between two neurons. Bi has determined that this reverberation can either strengthen or weaken a synapse, depending on the precise timing of pre- and postsynaptic activity. In addition, he has found that this activity-induced synaptic modulation can spread to specific neighboring synapses. Bi and his laboratory are working to characterize a complete set of rules for activity-dependent synaptic modification and to elucidate the underlying cellular mechanisms. His findings are then being paired with those of theoreticians to create neural network models for additional insights into the functional implications of cellular modification and plasticity.

Centers Center for Neuroscience at the University of Pittsburgh Susan G. Amara, Ph.D. Alan F. Sved, Ph.D. (Department of Neuroscience, School of Arts and Sciences) Co-directors Center for the Neural Basis of Cognition Peter L. Strick, Ph.D. (University of Pittsburgh) Co-director

Carl R. Olson, Ph.D. (Carnegie Mellon University) Acting Co-director Center for Neuroanatomy with Neurotropic Viruses Peter L. Strick, Ph.D. J. Patrick Card, Ph.D. (Department of Neuroscience, School of Arts and Sciences) Co-directors Systems Neuroscience Institute Peter L. Strick, Ph.D. Director

Regular Faculty Endowed Chair Susan G. Amara, Ph.D. Dr. Thomas Detre Professor of Neuroscience and Chair

Chair in Systems Neuroscience (open) Professors Elias Aizenman, Ph.D. John P. Horn, Ph.D. Andrew B. Schwartz, Ph.D. Daniel J. Simons, Ph.D. Peter L. Strick, Ph.D. Associate Professors Willi S. Halfter, Ph.D. Allen L. Humphrey, Ph.D. H. Richard Koerber, Ph.D. Carl F. Lagenaur, Ph.D., Cynthia Lance-Jones, Ph.D. Laura E. Lillien, Ph.D. John B. Schumann, Ph.D. Joseph W. Yip, Ph.D.

Visiting Associate Professor Robert S. Turner, Ph.D. Research Associate Professors Richard P. Dum, Ph.D. Donna S. Hoffman, Ph.D. Assistant Professors Guo-Qiang Bi, Ph.D. Erika Fanselow, Ph.D. A. Paula Nichols, Ph.D. Edda Thiels, Ph.D. Gonzalo E. Torres, Ph.D. Research Assistant Professors Pakming Lau, Ph.D. Ole V. Mortensen, Ph.D. Nathalie Picard, Ph.D. Meel Velliste, Ph.D. Research Instructor Mee Hyang Choi, Ph.D.

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NEUROLOGICAL

SURGERY

DEPARTMENTS

Amin B. Kassam, M.D., Professor and Chair

DEPARTMENT PROFILE

The Department of Neurological Surgery is organized into various centers, including image-guided, functional, radiosurgery, endoscopic, skull base, cranial nerve and microvascular, spinal, exovascular and endovascular, pain control, trauma, and pediatric neurosurgery. The department offers clinical care aimed at maximizing patient recovery and outcomes and minimizing alterations in quality of life. For this reason, the department has focused on traditional surgical procedures while also implementing the growing fields of endoscopic transnasal surgery for intracranial tumor resection; stereotactic radiosurgery for intracranial and spinal tumor, pain syndrome, and vascular malformation treatment; endovascular surgery for vascular abnormalities and stroke; and percutaneous and minimally invasive approaches to spinal disorders. In addition to direct patient care, the department has an active basic and clinical research portfolio.

Residency and Fellowship Training

Selected Research Highlights

The neurological surgery residency program is an internationally renowned, six-year, accredited program with a reputation for training exceptional neurosurgeons. Residents receive training in a number of neurosurgical areas like pediatric, adult microvascular, trauma, spinal, vascular, stereotactic and image-guided surgery, neuroradiology, and neuropathology. Advanced residency training includes experience in complex spinal procedures, craniotomies for intraaxial tumors and meningiomas, and posterior fossa surgery. Residents also spend one to two years conducting clinical or basic science research on focused projects. Neurosurgical fellowships are also available, lasting from six months to two years, and currently include basic science research, image-guided neurosurgery, pediatric neurosurgery, spinal neurosurgery, endovascular neurosurgery, and skull base surgery.

Hideho Okada, M.D., Ph.D., has developed a vaccine approach to produce an immune response against gliomas, the lethal, difficult-to-treat primary tumors that aggressively invade the folds and creases of the brain. The vaccine is based on four tumor antigens commonly found on the surface of gliomas. Rather than taking antigens from a particular patient to evoke an immune response, Okada’s technique uses a more general collection of antigens. Because gliomas grow quickly, the time needed to isolate patient-specific peptides would allow the disease to progress to the point at which treatment would be futile. Okada’s vaccine uses a multi-antigen approach, in which four different peptides are modified to look more “dangerous” to the immune system, potentially eliciting a stronger immune response. C. Edward Dixon, Ph.D., leads a

research team that focuses on developing therapeutics for traumatic brain injury (TBI), which initiates pathological biochemical cascades that can persist long after event survival. Better understanding of these cascades and their attenuation by translatable therapies is the team’s primary goal. Specific studies involve nitrosative stress and PARP

(poly[ADP-ribose] polymerase) activation, statin therapies and their interaction with amyloid b in cell death, effects of calcineurin inhibition on neuronal death and plasticity, Fas-mediated cell death, and mechanisms underlying the endogenous beneficial effects of iNOS (inducible nitric oxide synthase). These studies allow Dixon and his team to correlate basic scientific investigations with human clinical TBI to define the acute and chronic molecular mechanisms of secondary brain injury and to identify treatments most likely to benefit TBI patients. Ian F. Pollack, M.D., and colleagues

are investigating novel strategies for brain tumor therapy, especially for pediatric brain tumors, which constitute the leading cause of cancerrelated deaths in children. Despite advances in neurosurgical, radiotherapeutic, and chemotherapeutic techniques, the overall prognosis of children with brain tumors has not improved significantly in the last decade. In fact, for a particular tumor class, gliomas, only 20 percent of patients survive long term. Pollack and his colleagues are exploring why there are such differences in individual response to therapy, even when considering clinical prognostic factors. The team has proposed that molecular and immunohistochemical markers may provide a means to supplement clinical and histological information to refine prognostic assessments. The study determined that differences in p53 mutation and expression, MIB-1 proliferation index, and fibroblast growth factor immunoreactivity are strongly correlated with progression-free and overall survival. Establishing exactly which markers are valid outcome predictors would allow molecular categorization of the tumors and could lead to risk-adapted stratification for future studies.

Michael B. Horowitz, M.D., and colleagues are studying aneurysmal subarachnoid hemorrhage (SAH) and resulting cerebral vasospasm, a complication that occurs in as many as 67 percent of SAH patients and contributes to death and disability. The team has determined that intravenous administration of magnesium sulfate within 48 hours of SAH significantly reduces symptomatic cerebral vasospasm incidence. In addition, Horowitz and colleagues have found that within five days after SAH, a subset of patients display elevated troponin I levels, which are indicative of myocardial ischemia and infarct. The team is evaluating the incidence of myocardial ischemia and infarct following SAH to determine whether myocardial ischemia increases symptomatic vasospasm risk. The research project focuses on catecholamine, which surges immediately after SAH and provides a common mechanism for vasospasm of both myocardial and cerebral vessels.

Centers Center for Clinical Neurophysiology Robert J. Sclabassi, M.D., Ph.D. Director

Brachial Plexus and Peripheral Nerve Injury Center and Clinic P. David Adelson, M.D. Director Center for Injury Research and Control (CIRCL) Harold B. Weiss, Ph.D., M.P.H. Director Center for Image-Guided Neurosurgery L. Dade Lunsford, M.D. Douglas Kondziolka, M.D., M.Sc. Co-directors Minimally Invasive endoNeurosurgery Center (MINC) Amin B. Kassam, M.D. Director Center for Endovascular and Exovascular Therapy Michael B. Horowitz, M.D. Director Cranial Nerve Disorders Program Amin B. Kassam, M.D. Director Skull Base Surgery Center Amin B. Kassam, M.D. Carl H. Snyderman, M.D. (Department of Otolaryngology) Co-directors Neurosurgical Spine Services Division Richard Spiro, M.D. Director

Community Neurosurgery Tri-State Neurosurgical Associates Joseph C. Maroon, M.D. Director

Center for Surgical Pain Management John J. Moossy, M.D. Director

Westmoreland County Community Neurosurgery Michael J. Rutigliano, M.D., M.B.A. Director

Pediatric Neurosurgery at Children’s Hospital of Pittsburgh Ian F. Pollack, M.D. Chief

Brain and Spine Injury Center David O. Okonkwo, M.D., Ph.D. Clinical Director

Surgical Epilepsy Center P. David Adelson, M.D. Director

Brain Trauma Research Center C. Edward Dixon, Ph.D. Director

Surgical Neuro-Oncology Center Arlan Mintz, M.D., M.Sc. Surgical Co-director, Adult

Pediatric Neurotrauma P. David Adelson, M.D. Director

Ian F. Pollack, M.D. Surgical Co-director, Pediatric Frank S. Lieberman, M.D. (Department of Neurology) Medical Co-director

Regular Faculty Endowed Chairs P. David Adelson, M.D. Dr. A. Leland Albright Professor of Children’s Neurosurgery

Douglas Kondziolka, M.D., M.Sc. Dr. Peter J. Jannetta Professor L. Dade Lunsford, M.D. Lars Leksell Professor Ian F. Pollack, M.D. Dr. Walter E. Dandy Professor Peter E. Sheptak Chair in Neurological Surgery (open) Distinguished Professor L. Dade Lunsford, M.D. Professors C. Edward Dixon, Ph.D. Michael B. Horowitz, M.D. Larry W. Jenkins, Ph.D. Amin B. Kassam, M.D. John J. Moossy, M.D. Robert J. Sclabassi, M.D., Ph.D. Mingui A. Sun, Ph.D. Associate Professors Jeffrey R. Balzer, Ph.D. Peter C. Gerszten, M.D., M.P.H. Ajay Niranjan, M.B.B.S. Hideho Okada, M.D., Ph.D. Harold B. Weiss, Ph.D., M.P.H. Assistant Professors David J. Bissonette, M.B.A. Boyle C. Cheng, Ph.D. Donald J. Crammond, Ph.D. Anthony Fabio, Ph.D. Glenn T. Gobbel, D.V.M., Ph.D. Paola Grandi, Ph.D. Arlan Mintz, M.D., M.Sc. David O. Okonkwo, M.D., Ph.D. Miguel Ernes Habeych Sanmiguel, M.D. Richard Spiro, M.D. Elizabeth Christi Tyler-Kabara, M.D., Ph.D. Research Assistant Professors Wendy F. Mayle, M.A. Hong Qu Yan, M.D.

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NEUROLOGY

Steven T. DeKosky, M.D., Professor and Chair

DEPARTMENT PROFILE

The Department of Neurology offers state-of-the-art-diagnostic and treatment services to patients with a variety of neurological disorders. Residents are provided with high quality clinical training in combination with excellence in research, which includes both basic and clinical investigations aimed at examining the processes that underlie many disorders of the nervous system. Together, these departmental foci provide comprehensive, cutting-edge patient care, training of future neurologists, and research for the advancement of neurological understanding and treatment.

Residency and Fellowship Training

Selected Research Highlights

Because of the relationship between the department and UPMC, residents in neurology are trained to a high level of competence in diagnosing and treating neurological disorders, interpreting diagnostic techniques, developing core knowledge in clinical and basic neurosciences, and searching for information from a variety of electronic sources. The University provides training resources through its world-renowned Department of Neuroscience, a full-time neurology staff, top-level treatment facilities in western Pennsylvania, and a 3:1 ratio of full-time faculty to residents. Clinical training covers such areas as movement disorders, stroke, neuromuscular conditions, epilepsy, neuro-oncology, neuro-otology, neuro-ophthalmology, cognitive and memory disorders, and multiple sclerosis. Advanced training includes pediatric neurology and electives in electroencephalography (EEG), electromyography (EMG), carotid duplex, neurosurgery, psychiatry, and basic neuroscience research.

Paula R. Clemens, M.D., studies gene therapy for the treatment of skeletal diseases, with a primary focus on Duchenne muscular dystrophy (DMD) and muscle cachexia. Her laboratory has successfully delivered systemic marker genes and minidystrophin constructs to skeletal muscles of fetal mouse pups in utero using an adeno-associated viral vector. Prenatal diagnosis of DMD is possible, and the disease pathology is well established before birth. The gene therapy technique developed by Clemens and her team would allow widespread therapeutic gene transfer to skeletal muscle at the earliest possible stage. The researchers are also pursuing a preclinical study using NF-kB (nuclear factor kappa B) activation as a means to amerliorate disease pathology in DMD.

Using the invertebrate model Caenorhabditis elegans, Miguel Estevez, M.D., Ph.D., studies amyotrophic lateral sclerosis (ALS) and epilepsy. His ALS model is produced by exposure to selenium, a known human motor neuron toxicant. The Estevez laboratory has developed many selenium-resistant C. elegans mutations, which show resistance to selenium’s neurotoxic effects. These studies have highlighted the mitogenactivated protein kinase-associated

neurodegenerative cascade that works through an insulin-like growth factor as well as mutations in a superoxide dismutase gene, which is involved in human ALS-type neurodegeneration. Estevez plans to develop an RNA interference technique to confer selenium toxicity resistance and determine its effect on human ALS. Cognition in Alzheimer’s patients can be improved with the use of computer-based tasks aimed at increasing mental activity and enhancing mental function. Oscar L. Lopez, M.D., and collaborators in Barcelona, Spain, have determined that Internet-based computer activity, in combination with common Alzheimer’s medications, is more successful at improving cognition than traditional cognitive therapies aimed at dementia. Their study has determined that study participants who received traditional cognitive therapy in combination with Internet-based therapy showed 24 weeks of significant improvement on standard cognitive function and performance measures compared to both the control (untreated) and traditional cognitive therapy groups. While the traditional therapy did produce cognitive improvements over the control group, the effect lasted only 12 weeks, and by 24 weeks had disappeared.

Centers Alzheimer Disease Research Center Steven T. DeKosky, M.D. Director Commonwealth of Pennsylvania Center of Excellence on Detection, Diagnosis, and Intervention in Dementia Steven T. DeKosky, M.D. Director Comprehensive Epilepsy Center Director, Adult Section (open)

Patricia K. Crumrine, M.D. (Department of Pediatrics) Director, Pediatric Section Pittsburgh Institute for Neurodegenerative Diseases J. Timothy Greenamyre, M.D., Ph.D. Director Stroke Institute Lawrence R. Wechsler, M.D. Director Udall Center for Parkinson’s Research Michael J. Zigmond, Ph.D. Director University of Pittsburgh Headache Center Robert G. Kaniecki, M.D. Director

Regular Faculty Endowed Chairs Steven H. Graham, M.D., Ph.D. Connolly Family Professor in the Stroke Institute

J. Timothy Greenamyre, M.D., Ph.D. UPMC Professor of Movement Disorders in Neurology Robert Y. Moore, M.D., Ph.D. Love Family Professor of Neurology

Professors Jun Chen, M.D. Steven T. DeKosky, M.D. David Lacomis, M.D. Oscar L. Lopez, M.D. Lawrence R. Wechsler, M.D. Michael J. Zigmond, Ph.D. Associate Professors Paula R. Clemens, M.D. John J. Doyle, M.D. Teresa G. Hastings, Ph.D. Frank S. Lieberman, M.D. Galen W. Mitchell, M.D. Judith A. Saxton, Ph.D. Assistant Professors Anto Ivo Bagic, M.D. Sarah Beth Berman, M.D., Ph.D. Edward Alan Burton, M.B.B.S. Miguel Estevez, M.D., Ph.D. R. Wesley Farris II, M.D. Kathy Lou Gardner, M.D. Gena R. Ghearing, M.D. Max Daniel Hammer, M.D. Ricky Hendrickson, Ph.D. Rock A. Heyman, M.D. David A. Hinkle, M.D., Ph.D. Samay Jain, M.D. Tudor Gheorghe Jovin, M.D. Robert G. Kaniecki, M.D. Eric A. Ogren, M.D. Ruth G. Perez, Ph.D. Chitharanjan Rao, M.B.B.S. Vivek Reddy, M.D. Lisa C. Roeske-Anderson, M.D. Michael J. Soso, M.D., Ph.D. Ken Uchino, M.D. Anne C. Van Cott, M.D. David B. Watson, M.D. David A. Wolk, M.D. Sasa Zivkovic, M.D. Visiting Assistant Professor Deric Minwoo Park, M.D. Research Assistant Professors Guo Dong Cao, Ph.D. Eric Konrad Hoffman, Ph.D. Milos D. Ikonomovic, M.D. Rehana Khan Leak, Ph.D. Kian-Fong Liou, Ph.D. Ronda R. Pindzola, Ph.D. Amanda D. Smith, Ph.D. Olga V. Vergun, Ph.D.

DEPARTMENTS

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W. Allen Hogge, M.D., Milton Lawrence McCall Professor and Chair

DEPARTMENT PROFILE

The Department of Obstetrics, Gynecology, and Reproductive Sciences provides clinical care in a wide array of gynecologic and obstetric specialties, including services for women with complications of pregnancy, gynecologic problems and malignancies, infertility and endocrine disorders, consultation needs in infectious diseases and genetics, and diagnostic ultrasound services. Much of the department’s research is conducted at Magee-Womens Research Institute (MWRI), which emphasizes innovative and interactive translational research. Faculty members at MWRI provide expertise in clinical and fundamental research, epidemiology, and health services research. The department includes the following divisions: Developmental and Regenerative Medicine, Diagnostic Ultrasound, Gynecologic Oncology, Gynecologic Specialties, Maternal-Fetal Medicine, Reproductive Endocrinology and Infertility, Reproductive Genetics, Reproductive Infectious Diseases and Immunology, and Urogynecology and Pelvic Reconstructive Surgery.

Residency and Training Programs

The department’s residency program balances academic and scholarly activities with clinical experience in inpatient and ambulatory medicine, adult intensive care, geriatrics, and surgical emergency room rotations. Training is designed to prepare a physician as both an obstetrician/ gynecologist and as a primary care physician. Residents are required to complete a clinical or basic science research project and present their work at the annual T. Terry Hayashi Resident Research Day. In addition, the department offers a variety of fellowships. The Fellowship in Female Pelvic Medicine and Reconstructive Surgery provides clinical and basic research training as well as exposure to NIH-funded trials through the urinary incontinence treatment network and the clinical trials network for pelvic floor disorders. Expertise in family planning, including international population control, is promoted through the Family Planning and Contraception Fellowship. The Genetics Fellowship offers broad exposure to clinical and laboratory research experiences and specialized

training in the role of heredity in gynecologic cancer. The MaternalFetal Medicine Fellowship provides training in ultrasound procedures, neonatology, statistical methodology, and basic or clinical research. The Reproductive Infectious Diseases and Immunology Fellowship focuses on infectious diseases, including sexually transmitted diseases and neonatal infections in obstetric and gynecologic patients. Divisions Developmental and Regenerative Medicine Gerald P. Schatten, Ph.D. Director

The Division of Developmental and Regenerative Medicine focuses on clinical, translational, and fundamental research and education encompassing developmental and reproductive biology, prenatal medicine, and stem cells for regenerative medicine. The division’s core resources encompass assisted reproductive technologies, imaging, transgenic and molecular research, and education and outreach.

Diagnostic Ultrasound Lyndon M. Hill, M.D. Chief

Gynecologic Specialties Mitchell D. Creinin, M.D. Chief

The Diagnostic Ultrasound Division performs 45,000 obstetric and gynecologic examinations each year, including sonograms, Doppler studies, sonographically guided amniocentesis procedures, and specialty procedures like ovarian cyst aspiration and sonographic guidance for operative cases. Research includes assessment of amniotic fluid volume in normal twin gestations, determination of twin chorionicity and amnionicity, evaluation of adnexal masses in pregnancy, and the validation of transabdominal ultrasound in detection of a two-vessel umbilical cord. Research has contributed to the creation of CD-ROM programs on placental pathology and other conditions and Web-based programs on biophysical profile score, oligohydramnios, and ectopic pregnancy.

The Division of Gynecologic Specialties provides consultation, evaluation, and care for women with gynecological needs related to infectious diseases, family planning, menopause and geriatric gynecology, vulvar disorders, cervical dysplasia, pelvic pain management, minimally invasive pelvic surgery, and adolescent gynecology. Division research includes screening and management of preneoplastic disease, endoscopic surgery, nonsurgical treatment of urinary incontinence, and the molecular biology of pelvic organ prolapse.

Gynecologic Oncology Joseph L. Kelley III, M.D. Chief

The Division of Gynecologic Oncology treats gynecologic malignancies, directs chemotherapy, oversees radiation therapy, and performs gastrointestinal and genitourinary surgery. Clinical initiatives include the Ovarian Cancer Assessment and Surveillance Program and the Ovarian Cancer Center of Excellence. In addition, the division maintains a specimen bank for oncological study. Division research primarily investigates cancer immunology, quality of life during cancer treatment, and molecular analysis of human tumors. This research is done in conjunction with the University of Pittsburgh Cancer Institute, Magee-Womens Research Institute, and the UPMC Gynecologic Oncology Group.

Maternal-Fetal Medicine Steve N. Caritis, M.D. Chief

The Division of Maternal-Fetal Medicine provides clinical care for women with complications of pregnancy and provides education about normal and high-risk obstetrics for medical students, residents, nurses, and practicing obstetricians. Division research focuses on preeclampsia development and expression; epidemiologic factors contributing to perinatal mortality; preterm labor treatment, prediction, and relation to infectious diseases; diabetes and pregnancy; renal disease in pregnancy; smoking; and maternalfetal pharmacology. The division supervises the Magee-Womens Hospital midwife practice. Reproductive Endocrinology and Infertility Joseph S. Sanfilippo, M.D. Chief

The Division of Reproductive Endocrinology and Infertility evaluates and manages infertility and endocrine disorders relating to reproduction. Clinical programs provide patients with state-of-the-art assisted reproductive techniques.

The division coordinates basic and clinical research involving individuals with reproductive and endocrine disorders through collaborative investigations involving reproductive neuroscience, clinical epidemiology, molecular biology, ovarian physiology, and the physiology of puberty. Reproductive Genetics Brian A. Clark, M.D., Ph.D. Chief

The Division of Reproductive Genetics provides genetic counseling and clinical evaluation as well as dysmorphology consults for infants, children, and adults suspected of having genetic disease. Cancer risk analysis is available to women with a family history of breast cancer or gynecologic malignancies. The division’s Pittsburgh Cytogenetics Laboratory conducts peripheral blood, bone marrow, maternal serum screening, and other types of tests. Division research includes the etiology of recurrent pregnancy loss and the genetic basis of tumor formation. Reproductive Infectious Diseases and Immunology Harold C. Wiesenfeld, M.D.C.M. Chief

The Division of Reproductive Infectious Diseases and Immunology focuses on infections of the female reproductive tract and their effect on women’s health. The division’s multidisciplinary patient care team includes specialists in clinical infectious diseases, microbiology, immunology, virology, epidemiology, and molecular biology. Division research includes studies on pelvic inflammatory disease; genital tract mucosal immune response; the epidemiology of recurrent pregnancy loss, preterm delivery, and intrauterine growth restriction; maternal antibody and group B streptococcal neonatal infection; female HIV infection; molecular diagnostics of sexually transmitted diseases; intrauterine fetal infection; and intra-amniotic infection.

Urogynecology and Pelvic Reconstructive Surgery Halina M. Zyczynski, M.D. Chief

The Division of Urogynecology and Pelvic Reconstructive Surgery is part of the Center for Continence and Pelvic Floor Disorders at MageeWomens Hospital of UPMC. The center offers consultations and diagnostic and treatment services for women with pelvic floor disorders, including pelvic organ prolapse and fecal or urinary incontinence. Clinicians include experts in urogynecology and reconstructive pelvic surgery, urology, neurourology, minimally invasive surgery, pelvic pain management, gastroenterology, colorectal surgery, geriatrics, and physical therapy. The most current research and clinical standards are used to provide individualized treatment plans, which may involve behavioral, medical, nonsurgical, and surgical approaches. Selected Research Highlights Carl A. Hubel, Ph.D., and colleagues have studied factors underlying preeclampsia in pregnant women. Women with preeclampsia develop activating angiotensin II type 1 autoantibodies (AT1-AAs) and experience increases in insulin resistance and serum concentrations of soluble fms-like tyrosine kinase 1 (sFlt-1). Hubel and colleagues measured AT1-AAs, sFlt-1, insulin resistance, and related cardiovascular risk factors in groups of women with previous preeclampsia and previous normal pregnancies at nine to 27 months after the first completed pregnancy. AT1-AAs were detected in significantly more women with previous preeclampsia (17.2 percent) than with previous uncomplicated pregnancies (2.9 percent). Women with activating autoantibodies also had significantly increased sFlt-1 and higher insulin resistance compared with autoantibody-negative women.

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The researchers concluded that, like sFlt-1, AT1-AA does not regress completely after delivery, and correlations may exist among these preeclampsia-induced variables. Because expression of the active form of cellular matrix metalloproteinase-1 (MMP-1) tends to weaken pelvic floor integrity, Pamela A. Moalli, M.D., Ph.D., and colleagues have investigated the effect of sex steroid hormones on MMP-1 expression in fibroblasts derived from pre- and postmenopausal women undergoing prolapse repair. The fibroblasts were treated with physiologic concentrations of 17beta-estradiol (E2), progesterone, E2 plus progesterone, and E2 plus the antiestrogen ICI 182,780. The researchers analyzed the latent, active, and fragment forms of MMP-1 to establish cellular expression levels. All treatments, except that with ICI 182,780, increased the latent and fragment forms of MMP-1. However, the active form of MMP-1 was only decreased significantly in the presence of E2 plus progesterone. Based on these results, Moalli and colleagues established that maintaining pelvic floor integrity through decreased MMP-1 expression can be accomplished only in the presence of both sex steroid hormones. Limited data describe long-term effects of nonoxynol-9 spermicidal contraceptives on the vaginal microbial ecosystem. Sharon L. Hillier, Ph.D., and colleagues obtained vaginal swabs from women in a randomized clinical trial before initial use of one of five different nonoxynol-9 formulations. Up to three more samples were gathered over seven months of use, and the researchers evaluated the prevalence of several constituents of the normal vaginal flora. Overall changes in vaginal microbes after nonoxynol-9 use were minimal for each formulation, indicating minimal disruption

of vaginal ecology. However, when the researchers considered both nonoxynol-9 concentration and frequency of use, they found a dosedependent increase in prevalence of anaerobic gram-negative rods, peroxide-negative lactobacilli, and bacterial vaginosis. Hillier and colleagues concluded that moderate use of nonoxyl-9, regardless of concentration, does not change vaginal microflora but that increased exposure elevates the risk of bacterial vaginosis and its associated flora. The risk of preterm birth has been linked to a common gynecological infection called bacterial vaginosis (BV). Hyagriv N. Simhan, M.D., M.S.C.R., and colleagues have determined that the BV-associated risk for preterm birth increases when one partner is African-American. The clinical study evaluated women in their first trimester of pregnancy for the presence of BV. Generally, BV was less common among white women than black women; however, Simhan and colleagues showed that partner race influences BV risk. When at least one partner is black, whether male or female, the risk of BV doubles. Preterm birth contributes to more than one-third of infant deaths, according to the Centers for Disease Control and Prevention, and little is known about its underlying causes. Simhan and colleagues plan to investigate the factors contributing to the BV-associated increases in preterm birth risk but have already concluded that any solutions will not be a matter of simply treating the woman. At least 15 percent of clinically recognized pregnancies end in early pregnancy failure (EPF); and, for many women, the products of conception are not spontaneously aborted, requiring medical intervention. Mitchell D. Creinin, M.D., and colleagues previously found that misoprostol, a vaginal medication, worked as well as surgical curettage for intervention following EPF. They

subsequently examined bleeding patterns following misoprostol or curettage use and determined that bleeding is heavier and more prolonged with misoprostol than with curettage (although rarely requiring intervention) and that the heavier misoprostol-induced bleeding correlates with greater decreases and larger changes in hemoglobin levels. Creinin and colleagues suggest that while both treatments are safe, women should be informed of the differences.

Institute Magee-Womens Research Institute Yoel Sadovsky, M.D. Scientific Director

Regular Faculty Endowed Chairs W. Allen Hogge, M.D. Milton Lawrence McCall Professor and Chair

Yoel Sadovsky, M.D. Elsie Hilliard Hillman Professor of Women’s and Infants’ Health Research Professors Steve N. Caritis, M.D. Mitchell D. Creinin, M.D. Daniel Israel Edelstone, M.D. Lyndon M. Hill, M.D. Sharon L. Hillier, Ph.D. Kathleen McIntyre-Seltman, M.D. James M. Roberts, M.D. Joseph S. Sanfilippo, M.D. Gerald P. Schatten, Ph.D. Visiting Professors Brian A. Clark, M.D., Ph.D. Robert P. Edwards, M.D. Associate Professors Julie A. DeLoia, Ph.D. Richard S. Guido, M.D. Laura Hewitson, Ph.D. Joseph L. Kelley III, M.D. Marijane A. Krohn, Ph.D. Mary Ann Portman, M.D. Calvin Randall Simerly, Ph.D. Margaret L. Watt-Morse, M.D. Harold C. Wiesenfeld, M.D.C.M. Halina M. Zyczynski, M.D.

Visiting Associate Professors Charlene S. Dezzutti, Ph.D. David Gerard Peters, Ph.D. Robert L. Thompson, M.D. Morris E. Turner, M.D. Research Associate Professors Bernard John Moncla, Ph.D. Paul J. Sammak, Ph.D. Assistant Professors Aletha Yvette Akers, M.D. Judith L. Balk, M.D. Richard H. Beigi, M.D. Judy C. Chang, M.D. Tianjinao Chu, Ph.D. Bonnie A. Coyne, M.D. Ashi Daftary, M.D. Stephen Paul Emery, M.D. Robert H. Gedekoh, M.D. Chiara G. Ghetti, M.D. Gabriella G. Gosman, M.D. Jennifer Lynn Hayes, M.D. Lih-Ching Hsu, Ph.D. Jie Hu, M.D., Ph.D. Carl A. Hubel, Ph.D. Arundhathi Jeyabalan, M.D. Brinda N. Kalro, M.D. Robert J. Kaminski, M.D. David E. Kauffman, M.D. Marta Christine Kolthoff, M.D. Thomas C. Krivak, M.D. Margaret D. Larkins-Pettigrew, M.D. Jean J. Latimer, Ph.D. Jerry L. Lowder, M.D. Suketu M. Mansuria, M.D. Pamela A. Moalli, M.D., Ph.D. Christopher S. Navara, Ph.D. Kyle E. Orwig, Ph.D. Robert W. Powers Jr., Ph.D. Matthew Fontaine Reeves, M.D. Hyagriv N. Simhan, M.D., M.S.C.R. Paniti Sukumvanich, M.D. Gary Sutkin, M.D. Glenn Michael Updike, M.D. Anda Mioara Vlad, Ph.D. Kristin K. Zorn, M.D. Visiting Assistant Professors Janet M. Catov, Ph.D. Thomas L. Cherpes, M.D. Research Assistant Professors Diane L. Carlisle, Ph.D. Augustine Rajakumar, Ph.D.

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DEPARTMENT PROFILE

The Department of Ophthalmology is committed to advancing eye care through research, clinical trials, and teaching in an active clinical service that provides comprehensive and subspecialty ophthalmic care. The department includes the following sections: cornea, anterior segment, external disease and refractive surgery, comprehensive ophthalmology, glaucoma, neuro-ophthalmology, ophthalmic genetics, oculoplastics and trauma, pediatric ophthalmology, and retina and vitreous surgery. Research programs address fundamental questions of ocular biology and vision as well as potential new therapies for serious eye disorders, with a strong focus on corneal tissue engineering; ocular immunology and wound healing; ocular imaging; technology discovery and computer software development for image processing and analysis; the molecular biology, proteomics, and genomics of retinal and corneal development; and infectious disorders.

Residency and Fellowship Training

The Department of Ophthalmology trains residents in a three-year, accredited program in medical and surgical ophthalmology in facilities at the Eye & Ear Institute and VA Pittsburgh Healthcare System and in an intensive clinical and surgical service at the University of New Mexico in Albuquerque. Residents can also take advantage of the Ophthalmology Surgical Training Laboratory, which allows the practice of medical techniques and procedures before entering an operating room. All residents are required to collaborate with faculty in clinical research. The department offers fellowships in several areas of ophthalmology, including cornea, glaucoma, oculoplastic surgery, pediatric ophthalmology and strabismus, and vitreoretinal surgery. Selected Research Highlights Paul R. Kinchington, Ph.D., in collaboration with researchers at Erasmus Medical Center in Rotterdam, The Netherlands, has studied primary infection with herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV), both of which result in lifelong latent infections of sensory ganglia neurons like the trigeminal ganglia (TG). It is believed that T cells play a role in viral latency, and the researchers observed high

numbers of activated CD8+ T cells expressing a late effector memory phenotype in latently infected TG. However, the activity of the CD8+ T cells was directed against HSV-1 and not VZV, despite neuronal expression of VZV proteins. Kinchington and colleagues concluded that herpesvirus latency in human TG is associated with a local, persistent T-cell response but that these cells do not appear to directly control VZV latency in human TG. Understanding the mechanisms behind viral latency will aid in the eventual development of therapeutic interventions. Corneal stroma keratocytes secrete a specialized extracellular matrix essential for vision but exhibit limited capacity for self-renewal and become fibroblastic, secreting nontransparent tissue, after cell division. James L. Funderburgh, Ph.D., and Nirmala Sundar Raj, Ph.D., have sought to identify progenitor cells for human keratocytes. Near the corneal limbus, stromal cells express ABCG2, a protein present in many adult stem cells. The researchers isolated the ABCG2expressing cell population, which exhibited clonal growth and continued to express ABCG2 plus PAX6, a homeobox gene product not expressed in adult keratocytes. As molecular markers of keratocytes increased in

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the cultured isolated cells, ABCG2 and PAX6 expression was lost. These results demonstrate a cell population in the human corneal stroma expressing stem cell markers that appear to be the first human cells identified with keratocyte progenitor potential. Future analyses of these cells could elucidate molecular mechanisms underlying corneal development, differentiation, and wound healing and may provide a resource for corneal stroma bioengineering and cell-based therapeutics. One potential side effect of laser in situ keratomileusis (LASIK) surgery is diffuse lamellar keratitis (DLK). Because many clinicians use a prophylactic antibiotic following surgery, Jerold S. Gordon, M.D., and Francis S. Mah, M.D., have investigated whether the topical fluoroquinolone antibiotics could cause DLK. Using a rabbit model, the researchers created LASIK flaps and treated with ciprofloxacin 0.3%, ofloxacin 0.3%, balanced salt solution (BSS), or Pseudomonas aeruginosa endotoxin before flap closure and continued to apply the same drug four times daily following the procedure. Gordon and Mah observed significantly higher median DLK scores with ciprofloxacin, ofloxacin, and the endotoxin compared to the BSS control. Ciprofloxacin produced DLK more often and with higher median scores than ofloxacin or the endotoxin. The researchers then used an endotoxininduced model, in which all LASIK flaps were treated with the endotoxin followed by ciprofloxacin, ofloxacin, or BSS, and found that ciprofloxacin produced significantly higher DLK scores than the other two treatments. Gordon and Mah concluded that topical fluoroquinolones caused and exacerbated DLK in rabbit models and that ciprofloxacin was associated with more DLK than ofloxacin, suggesting the need for further assessment in clinical trials.

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Centers Charles T. Campbell Ophthalmic Microbiology Laboratory Jerold S. Gordon, M.D. Director Ophthalmology and Visual Sciences Research Center Robert L. Hendricks, Ph.D. Director

Regular Faculty Endowed Chairs Robert L. Hendricks, Ph.D. Joseph F. Novak, M.D., Professor of Ophthalmology Research

Joel S. Schuman, M.D. Eye & Ear Foundation Professor and Chair of Ophthalmology; Professor of Bioengineering E. Ronald Salvitti, M.D., Chair in Ophthalmology (open) Professors Thomas R. Friberg, M.D. Jerold S. Gordon, M.D. Richard W. Hertle, M.D. Associate Professors Deepinder K. Dhaliwal, M.D. Andrew W. Eller, M.D. James L. Funderburgh, Ph.D. Paul R. Kinchington, Ph.D. Jes K. Klarlund, Ph.D. Robert J. Noecker, M.D. Nirmala Sundar Raj, Ph.D. Research Associate Professor Regis P. Kowalski, M.S. Assistant Professors Richard A. Bilonick, Ph.D. Gabrielle R. Bonhomme, M.D. Larissa Camejo, M.D. Puwat Charukamnoetkanok, M.D. Hiroshi Ishikawa, M.D. Francis S. Mah, M.D. Kyle C. McKenna, Ph.D. Hazem Samy, M.B.Ch.B. Robert M.Q. Shanks, Ph.D. S. Tonya Stefko, M.D. Evan L. Waxman, M.D., Ph.D. Xiangyun Wei, Ph.D. Gadi Wollstein, M.D. Dongsheng Yang, Ph.D. Research Instructor Lawrence E. Kagemann Jr., M.S.

The Department of Orthopaedic Surgery is committed to delivering high quality diagnostic and therapeutic patient care to adults and children with a diverse spectrum of orthopaedic disorders. The department integrates the latest biological and technological advancements in orthopaedic science and leads the development of innovative treatments through research. One technology unique to this department is the Computer Assisted Surgical Planning and Robotics (CASPAR) system, which is being assessed for use in accurate ligament placements during surgery. The department achieves balance through an outstanding training program, preeminent research that aggressively seeks to advance treatment of orthopaedic problems, and recognition that patients’ needs are central.

Residency and Fellowship Training

Selected Research Highlights

The Department of Orthopaedic Surgery is committed to the successful training of residents and fellows as well as continued education for attending orthopaedic surgeons. The training program prepares residents for a successful career in academic or clinical orthopaedic surgery, with an emphasis on disorders ranging from complex trauma to musculoskeletal tumors. The diversity of the department’s residency programs attracts top candidates from around the world. All residents are required to present clinical outcome projects at national meetings, and half of all residents are selected to enter a research track residency in which they conduct basic research and are expected to publish and present this work. Fellowship opportunities are available in foot and ankle surgery, hand and upper extremity surgery, spinal surgery, sports medicine, trauma surgery, and adult reconstruction.

Johnny Huard, Ph.D., and colleagues

have shown that muscle-derived stem cells (MDSCs) transplanted into dystrophic mice (mdx) can efficiently regenerate skeletal muscle. However, MDSC populations exhibit heterogeneous marker profiles and variability in regeneration abilities. The researchers found that cell sex influences MDSCs’ regeneration abilities. Female MDSCs (F-MDSCs) regenerated skeletal muscle more efficiently than male MDSCs (M-MDSCs), regardless of the isolation techniques and cell cloning used to obtain the cells. Huard and colleagues believe this difference in regeneration potential may arise from innate sex-related differences in the cells’ stress responses rather than from hormonal or immune responses. The researchers observed that oxidative stress produces increased differentiation in M-MDSCs compared to F-MDSCs, which may provide an F-MDSC proliferative advantage that eventually increases muscle regeneration. Based on these findings, Huard and colleagues encourage researchers to report cell sex, a largely unexplored variable, and consider the implications of using only one sex in their studies.

Christopher D. Harner, M.D., and colleagues in the knee biomechanics laboratory have examined clinical outcomes following isolated lateral meniscal allograft transplantation. Patients who had undergone the procedure were interviewed two to six years following surgery. When possible, a complete physical examination was conducted and postoperative radiographs were obtained. The researchers found that 96 percent of patients believed their overall function and activity level improved following surgery. Harner and colleagues determined that joint space narrowing was similar in the lateral compartments of both the transplanted and contralateral knee and that earlier meniscal transplantation, before the onset of significant joint space narrowing, may result in improved outcomes. The researchers also observed that patients fixed with the bony technique had significantly better range of motion than the suture fixation group, indicating a significant advantage in the use of the bony fixation method to best improve knee range of motion.

Bone marrow cells are routinely accessed for clinical cartilage repair. Constance R. Chu, M.D., and colleagues have studied pellet cultures of adult human bone marrow-derived mesenchymal stem cells (hMSC) transduced with adeno-associated virus (AAV) green fluorescent protein (GFP) or AAV-transforming growth factor beta1 (TGFbeta1). The researchers also conducted in vivo studies in which AAV-GFP and AAVTGFbeta1-transduced hMSCs were implanted into the osteochondral defects of athymic rats. In pellet culture, Chu and colleagues observed GFP expression in situ through day 21 after transduction. For the in vivo model, GFP transgene expression was observed by in situ fluorescent surface imaging in 100 percent of the defects at two, eight, and 12 weeks postimplantation. The researchers also

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observed improved cartilage repair in osteochondral defects at 12 weeks after AAV-TGFbeta1-transduced hMSC implantation. Based on these results, Chu and colleagues conclude that AAV is a suitable vector for gene delivery to improve hMSC cartilage repair potential. Neurocognitive testing is an important tool to assess sports-related injuries and avoid the potential for additional injury from premature return to contact sports based on athletes’ self-report of symptoms. Michael W. Collins, Ph.D., Mark R. Lovell, Ph.D., and colleagues have used computerbased neurocognitive testing to detect postconcussive abnormalities two days after injury in athletes with a diagnosed concussion. Postinjury symptom scores (self-reported) and neurocognitive performance (testbased) were compared with preinjury (baseline) scores and with those of a noninjured athlete control group. The researchers found that in the concussed athlete group, 64 percent reported a significant increase in symptoms and 83 percent showed significantly poorer neurocognitive test results relative to their own baseline performance. In this study, adding neurocognitive testing resulted in a net sensitivity increase of 19 percent. Based on these results, Collins and colleagues concluded that reliance on athletes’ self-reported postconcussion symptoms is likely to result in underdiagnosis and may result in premature return to play. However, the combination of self-reported symptoms and neurocognitive testing significantly increases diagnostic accuracy for concussive injuries.

Hans-Christoph Pape, M.D., studies “damage control orthopaedics,” a concept that mandates stabilization of seriously injured patients prior to surgical repair of orthopaedic injuries. Pape and colleagues have examined whether differences in outcome for polytrauma patients can be attributed to the degree of initial surgery. The researchers examined multiple patients in the German Trauma Registry with pelvic ring fractures requiring surgery whose injury severity score was at least 16. The effects of duration (short, intermediate, and long) and timing (early, intermediate, and late) of the initial pelvic surgical stabilization were analyzed. Pape and colleagues found that longer surgical durations were associated with significantly higher rates of liver failure. In addition, earlier surgery times were associated with a significantly higher rate of renal failure, multiorgan failure, and mortality. The researchers noted that in patients with a higher injury severity score, procedures lasting less than three hours resulted in improved mortality and decreased rates of multiorgan failure and sepsis. Overall, Pape and colleagues found that early, short surgery as well as delayed surgery are associated with a lower rate of organ failure and mortality in patients with multiple injuries. Zong-Ming Li, Ph.D., and Robert A. Kaufmann, M.D., have studied

precision grip impairment caused by lower median nerve block at the carpal tunnel, which acutely simulates a median neuropathy. Individuals were asked to grip, lift, and hold an instrumented handle during a 60second period using precision grip both before and after nerve block. The investigators quantified precision grip by calculating the safety margin, which is the difference between actual grip force and the minimal grip force required to keep an object

from falling; the variation of grip force; and the migration area of center of pressure, which is defined by the center of pressure at a digittransducer surface. Median nerve block caused significant increases in the safety margin (>50 percent), grip force variation (>80 percent), and area of center of pressure migration (>250 percent). Fine motor control during precision grip was impaired, thus confirming the important role of sensory function in hand fine motor control. These findings can potentially be used to quantify hand function impairment caused by neuromuscular disorders, monitor hand disorder progress, and evaluate treatment efficacy.

Regular Faculty Endowed Chairs Freddie H. Fu, M.D., D.Sc. (Hon.), D.Ps. (Hon.) Dr. David Silver Professor and Chair

Christopher D. Harner, M.D. Blue Cross of Western Pennsylvania Professor Johnny Huard, Ph.D. Dr. Henry J. Mankin Professor James D. Kang, M.D. UPMC Professor of Orthopaedic Spinal Surgery Morey S. Moreland, M.D. Dr. William F. and Jean W. Donaldson Professor of Pediatric Orthopaedics Dr. Albert B. Ferguson Jr. Chair in Orthopaedic Surgery (open) Arthur J. Rooney Sr. Chair in Sports Medicine (open) Professor Gary S. Gruen, M.D. Associate Professors Constance R. Chu, M.D. William F. Donaldson III, M.D. Robert Goitz, M.D. Zong-Ming Li, Ph.D. Mark R. Lovell, Ph.D. Hans-Christoph Pape, M.D. Huicong Wang, Ph.D. W. Timothy Ward, M.D.

Visiting Associate Professors Mark Alvin Goodman, M.D. James J. Irrgang, Ph.D. Scott Tashman, Ph.D. Adolph J. Yates, M.D. Xudong Zhang, Ph.D. Assistant Professors Michael W. Collins, Ph.D. Lawrence S. Crossett, M.D. Vincent F. Deeney, M.D. Jeanne Marie Doperak, D.O. Jan S. Grudziak, M.D., Ph.D. Tanya J. Hagen, M.D. Robert A. Kaufmann, M.D. John Lee, M.D. Yong Li, M.D., Ph.D. Richard L. McGough III, M.D. Stephen A. Mendelson, M.D. Mark W. Rodosky, M.D. David A. Stone, M.D. Ivan Seth Tarkin, M.D. Bing Wang, M.D., Ph.D. Robin Vereeke West, M.D. Vonda Joy Wright, M.D. Dane Kent Wukich, M.D. Visiting Assistant Professors Jonathan Barclay Pollett, Ph.D. Thomas M. Sisk, M.D. Scott David Wissink, M.D. Research Assistant Professors Brigette M. Deasy, Ph.D. Burhan M. Gharaibeh, Ph.D. Rebecca K. Studer, Ph.D. Nam V. Vo, Ph.D. Instructor Jamie Eileen Lee Pardini, Ph.D.

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DEPARTMENT PROFILE

The goal of the Department of Otolaryngology is to continue to be a center of excellence for otolaryngology by providing high quality, state-of-the-art patient care, education, and research delivered in the most efficient and effective manner. Among the department’s faculty members are physicians with expertise in general otolaryngology as well as all subspecialties of the field, including head and neck surgery, otology / neurotology, balance disorders, cranial base surgery, allergy, sino-nasal disorders, voice and swallowing disorders, snoring and sleep apnea, maxillofacial trauma, facial plastic surgery, pediatric otolaryngology, and audiology and assisted listening devices.

Residency and Fellowship Training

The otolaryngology residency program is a five-year commitment, with the first year spent in a general surgery internship and the remaining four years in the department. Also available is a seven-year program that includes two years of research integrated with the five-year program. The decision to pursue the research track is not required until the third year of residency. Research is undertaken in an area of interest during the fifth and sixth postgraduate training years. On a limited basis, fellows may pursue a six-year postdoctoral training program in head and neck oncology. Fellowships are offered in otology/neurotology, head and neck oncology, cranial base surgery, pediatric otolaryngology, rhinology, and voice disorders. Selected Research Highlights Jennifer Grandis, M.D., has shown

that expression of STAT1 (signal transducers and activators of transcription 1) at levels higher than typically found in cancer cells may help prevent the spread of squamous cell cancer of the head and neck (SCCHN). Normally, STAT1 is expressed at lower levels in tumor cells than in normal cells, indicating that a loss of STAT1 may promote tumor growth. To test this theory, Grandis exposed SCCHN cells to chemotherapy alone or in combination with azacytidine, an agent that increases STAT1 production.

Those cells exposed to the drug combination were more responsive to treatment and more likely to stop growing and eventually die. More than two-thirds of SCCHN patients are at an advanced stage when diagnosed, and the disease carries a poor five-year survival rate. Current treatment options are limited, so the utility of gene therapy to increase STAT1 expression could have a positive effect on survival rates. Robert L. Ferris, M.D., Ph.D., is

identifying ways in which tumor cells evade the immune system. His laboratory has identified defective processing of tumor antigens (proteins) as a way that tumor cells can avoid recognition and elimination by the immune system. In particular, a peptide transporter complex inside tumor cells, called TAP1/2, was crucially important for head and neck cancer cells to be recognized and killed by tumor antigen-specific T lymphocytes, and it was lost in aggressive, metastatic cancers. These findings may explain the lack of clinical responses to cancer vaccines to date and point to improved efficacy of cancer immunotherapy in future vaccine trials. Joseph M. Furman, M.D., Ph.D.,

has observed in older persons that vestibular signals generated during rotation interfere with concurrent cognitive activity and, conversely,

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George K. Michalopoulos, M.D., Ph.D., Maud L. Menten Professor and Chair

that performance of a cognitive task modifies the characteristics of vestibular-induced eye movements. These findings suggest that loss of balance in older persons may be more likely while they are engaging in cognitive tasks or among those with cognitive impairment.

contraction, fetal fibroblasts exhibited higher contraction rates and a blunted response to exogenous PGE2 modulation. These findings indicate that fetal dermal fibroblasts are partially resistant to PGE2’s effects, which may have significant and specific relevance to the scarless fetal wound-healing phenotype.

Bill J. Yates, Ph.D., has observed that

vestibular signals generated during changes in posture specifically increase sympathetic nervous system outflow to regions of the body where blood pooling might occur, thereby shunting blood away from these areas. This response presumably contributes to maintaining consistent venous return to the heart, thereby preventing orthostatic intolerance. Shortly after dermal injury, cyclooxygenase-2 is upregulated and produces prostaglandin E2 (PGE2), which modulates both inflammatory and fibrotic wound-healing processes. Wound healing in fetal tissue has been shown to have altered PGE2 signaling and holds the unique property of being scarless. Patricia A. Hebda, Ph.D., Joseph E. Dohar, M.D., and Ha-Sheng Li-Korotky, M.D., Ph.D.,

have examined PGE2 regulation of fibroblast migration and contraction to determine whether the mechanisms in adult fibroblasts are conserved in fetal-derived dermal fibroblasts. The researchers observed that PGE2 inhibits both fetal and adult fibroblast migration in a dose-dependent manner, although fetal fibroblasts required a 10-fold higher PGE2 concentration to achieve adult inhibition levels. Disruption of the actin cytoskeleton was correlated with adult fibroblast migration inhibition while fetal dermal fibroblasts experienced no such disruption. The investigators then examined fibroblast contraction and found that, while PGE2 inhibited adult fibroblast

Regular Faculty Endowed Chairs Margaretha L. Casselbrant, M.D., Ph.D. Eberly Professor of Pediatric Otolaryngology

Jonas T. Johnson, M.D. Dr. Eugene N. Myers Professor and Chair Head and Neck Surgical Research Chair in Otolaryngology (open) Distinguished Professor Eugene N. Myers, M.D. Professors Carey D. Balaban, Ph.D. Charles D. Bluestone, M.D. Ricardo L. Carrau, M.D. William J. Doyle, Ph.D. David E. Eibling, M.D. Joseph M. Furman, M.D., Ph.D. Jennifer Grandis, M.D. Barry E. Hirsch, M.D. Carl H. Snyderman, M.D. Bill J. Yates, Ph.D. Associate Professors Cuneyt M. Alper, M.D. Joseph E. Dohar, M.D. Berrylin J. Ferguson, M.D. Robert L. Ferris, M.D., Ph.D. Suman Golla, M.D. Karl Kandler, Ph.D. Ellen M. Mandel, M.D. Clark A. Rosen, M.D. Barry M. Schaitkin, M.D. Robert F. Yellon, M.D. Research Associate Professors Patricia A. Hebda, Ph.D. Ha-Sheng Li-Korotky, M.D., Ph.D.

Assistant Professors David Hyunjoon Chi, M.D. Neeraj Gandhi, Ph.D. Jacqueline L. Gartner-Schmidt, Ph.D. Grant S. Gillman, M.D. Roxann Diez Gross, Ph.D. Stephen Y. Lai, M.D. David L. Mandell, M.D. Todd D. Otteson, M.D. Yael Raz, M.D. Libby Jo Smith, D.O. John Douglas Swarts, Ph.D. Elizabeth Hui-Yee Toh, M.B.B.S. Visiting Assistant Professors Seungwon Kim, M.D. Priya D. Krishna, M.D. Mariann McElwain, M.D., Ph.D. Jeffrey P. Simons, M.D. Ryan J. Soose, M.D. Research Assistant Professors Quan Cai, M.D. Ann M. Egloff, Ph.D. Sufi M. Thomas, Ph.D.

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Pathology exists at a crossroads between laboratory diagnostics and medical discovery. Pathologic analyses are often essential for clinical diagnoses, and diagnostic advances generally precede advances in therapeutics. In this rapidly evolving field, new techniques permit biochemical analysis of solid tissue samples, and advanced histologic methods are routinely used to detect abnormal cells in body fluids. Coordinated activities involving microbiology, histopathologic and electron microscopy, basic sciences, molecular diagnostics, and pathology informatics allow the Department of Pathology and its various divisions to support clinical and research efforts throughout the School of Medicine and UPMC. The divisions include Anatomic / Surgical Pathology – UPMC Presbyterian, Head and Neck Pathology, Neuropathology, Transplantation Pathology, Molecular Anatomic Pathology, Hematopathology, Immunopathology, Molecular Diagnostics, Clinical Chemistry, Clinical Microbiology, Transfusion Medicine, Magee-Womens Hospital Pathology, Pediatric Pathology – Children’s Hospital of Pittsburgh, Pathology at the VA Pittsburgh Healthcare System, Pathology at UPMC Shadyside, Community Pathology, Pathology Informatics, and Cellular and Molecular Pathology.

Residency and Fellowship Training

Divisions

The department offers residencies in anatomic pathology, clinical pathology, and combined training in both. Most residents train four to five years; the core program lasts three years, and additional elective time allows individuals to tailor the program to meet specific career objectives. The Clinical Fellowship Program provides advanced training in general surgical, head and neck, hematologic, gastrointestinal, genitourinary, and pulmonary pathology; other fellowships throughout the department emphasize advanced clinical training and research in a pathology subspecialty. The graduate program in cellular and molecular pathology, one of the disciplines included in the school’s Interdisciplinary Biomedical Graduate Program, combines Ph.D. level basic science and clinical research to explore fundamental questions related to the biology of normal tissue differentiation and growth as well as the cellular and molecular pathways leading to pathobiology of disease in human and animal models.

Anatomic Pathology Divisions

Samuel A. Yousem, M.D. Vice Chair Anatomic / Surgical Pathology — UPMC Presbyterian Samuel A. Yousem, M.D. Director

The Division of Anatomic/Surgical Pathology embraces emerging technologies to improve efficiency, progress, and daily function within hospitals and laboratories. Each year, the division examines 30,000 surgical and 13,000 cytology specimens and performs 350 autopsies. Particular emphasis is placed on oncogenesis and on pulmonary, soft tissue, orthopaedic, endocrine, and cytologic pathology. Division research includes general surgical pathology, pulmonary pathology, head and neck pathology, genitourinary pathology, and transplant pathology, all of which are supported by state-of-the-art medical informatics, sophisticated laboratories, and a highly developed human tissue banking facility.

Head and Neck Pathology Leon Barnes Jr., M.D. Director

The Division of Head and Neck Pathology specializes in all neoplastic and nonneoplastic diseases of the head and neck. In addition to routine histologies, the division provides specialized diagnostics using in situ hybridization, immunohistochemistry, electron microscopy, flow cytometry, and cytogenetics. Division research includes collaborative studies with the Department of Otolaryngology and the University of Pittsburgh Cancer Institute. Neuropathology Clayton A. Wiley, M.D., Ph.D. Director

The Division of Neuropathology is committed to finding new insights into the pathology of neurologic disease and to developing molecular therapeutics and diagnostic techniques. The division provides specialized services in the histologic examination of brain tissue as well as muscle and peripheral nerve biopsies. The division includes a multidisciplinary team of researchers investigating the pathogenesis of neurodegenerative disease, neurooncology, and developmental disorders using advanced anatomic, cellular, and molecular techniques. In addition, the division maintains a brain bank, providing essential access to postmortem human tissue for institutional researchers. Transplantation Pathology A.J. Demetris, M.D. Director

The Division of Transplantation Pathology plays an integral role in the organ transplantation program at UPMC in Pittsburgh as well as at the medical center’s satellite transplant center in Palermo, Italy. The division provides services in pre-transplant

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tissue typing as well as post-transplant tissue biopsies to look for lymphocyte reactivity, cytokine production, and detection of cytomegalovirus, Epstein-Barr virus, and hepatitis virus. The division maintains a Transplant Pathology Internet Service, a collaborative tool for transplant physicians and an interactive educational resource for health care professionals. Division research focuses on chimerism, viral infections, drug tolerance and toxicity, and malignancies in transplant patients. Molecular Anatomic Pathology Yuri Nikiforov, M.D., Ph.D. Director

The new Division of Molecular Anatomic Pathology (MAP) oversees existing and new molecular diagnostic tests based on tissue sections. In particular, the division uses molecular techniques to analyze gene expression patterns and genomic alterations in tissue sections to provide useful diagnostic information, especially to oncology groups. The MAP lab is of key importance for developing opportunities for translational research by members of the department. The lab works closely with the Division of Molecular Diagnostics to share techniques, know-how, and planning.

general hematology laboratories. The division has active consultation services, accepting fresh or previously fixed specimens for full evaluation or special studies. Division research concerns the role of cell signaling abnormalities in the development and progression of acute leukemia and the use of multiparameter approaches in the study of nonHodgkin’s lymphomas and related lymphoid proliferations, specifically mucosa-associated lymphatic tissue lymphomas, other extranodal B-cell lymphomas, diffuse large B-cell lymphomas, and post-transplant lymphoproliferative disorders.

infectious diseases, with emphasis on DNA and RNA viruses associated with solid organ transplantation; cooperates with the Department of Human Genetics in the Graduate School of Public Health to diagnose inherited disorders, including cystic fibrosis, Gaucher’s disease, and muscular dystrophy; and investigates the molecular basis of cell survival and apoptosis as well as oxidative mechanisms of disease, viral latency, hereditary cancer, and genetic disorders.

Immunopathology Bruce S. Rabin, M.D., Ph.D. Director

The Division of Clinical Chemistry coordinates a full range of biochemical analytic services for regional hospitals. Clinical support by the division includes therapeutic drug monitoring, toxicology analysis, hormone and tumor marker assays, biochemical tests for metabolic diseases, and nutrition and lipid analysis. The division conducts research in pharmacokinetics, assays of novel immunosuppressants, nutritional assessment of transplant patients, biomarkers for cancers, cholesterol biosynthesis during cell growth and regeneration, apoptosis, computer applications in clinical labs, and biochemical and molecular genetics of metabolic disorders.

The Division of Clinical Immunopathology offers a wide range of clinical testing procedures as well as patient evaluation and consultation for atopy, immunodeficiencies, acute and chronic infections, autoimmune disorders, and suitability for allografts. Division research is highly collaborative and includes investigations of the neural bases of stress and lymphocyte regulation, susceptibility to infectious diseases, stress-induced immune alterations, autoimmune diseases, hepatitis and HIV infections, and xenograft rejection.

Laboratory Medicine Section

Alan Wells, M.D., D.Med.Sci. Vice Chair

The Laboratory Medicine Section includes the following divisions: Hematopathology Steven H. Swerdlow, M.D. Director

The Division of Hematopathology provides diagnostic hematopathology, diagnostic lymph node/solid tissue services, and adult and pediatric bone marrow services. It supervises a large flow cytometry laboratory, a special hematology laboratory, and

Molecular Diagnostics Jeffrey A. Kant, M.D., Ph.D. Director

The Division of Molecular Diagnostics integrates molecular biology into the practice of pathology, translating complex techniques into simplified protocols suitable for use in a hospital diagnostic laboratory. Specifically, the division diagnoses and classifies neoplastic diseases with new, molecular-based markers to provide insight into prognosis and therapeutic monitoring of cancer patients for residual disease. The division also aids in the diagnosis of acquired

Clinical Chemistry Jorge Sepulveda, M.D., Ph.D. Acting Director

Clinical Microbiology A. William Pasculle, Sc.D. Director

The Division of Clinical Microbiology supports special sections in aerobic and anaerobic bacteriology, mycobacteria, and antibiotic sensitivity testing related to the diagnosis and treatment of legionellosis and atypical mycobacteria. The division promotes clinical and research activities in bacteriology, virology, and antiviral immunology, with emphasis on cytomegalovirus (CMV)

and Epstein-Barr virus infections after transplantation. It houses one of the nation’s four NIH-supported Multicenter AIDS Cohort Study groups involved in a major epidemiologic and laboratory study of inception and pathogenesis of HIV infection in gay men. Transfusion Medicine Darrell J. Triulzi, M.D. Director

The Division of Transfusion Medicine supports one of the largest transfusion services in the nation, handling more than 40,000 units of red cells and 40,000 units of platelets annually for adult and pediatric patients. Research in the division includes a multi-institutional NIH study of the immunologic effects of transfused leukocytes on patients with HIV; the role of leukoreduction in these patients to prevent alloimmuniation or transmission of cytomegalovirus infection to other patient populations like stem cell and organ transplant recipients; and blood use patterns in transplant patients, including the use of patient-specific strategies for autologous blood collection. Hospital-Based Divisions Magee-Womens Hospital Pathology David J. Dabbs, M.D. Director

This division specializes in perinatal, obstetric, neonatal, and gynecologic pathology and cytopathology; performs related diagnostic, teaching, and research activities; and provides specialized diagnostic services like flow cytometric analysis of gynecologic tumors, in situ hybridization techniques of microorganisms (particularly human papilloma virus), and immunohistochemical detection of estrogen and progesterone receptors in tumors. The division has assisted in developing new programs like Magee-Womens Hospital’s Comprehensive Breast Center and an ambulatory care program.

Pediatric Pathology — Children’s Hospital of Pittsburgh Ronald Jaffe, M.B.B.Ch. Director

The Division of Pediatric Pathology provides a full range of diagnostic services, including routine histopathology, molecular diagnostics, cytology, immunohistochemistry, in situ hybridization, ultrastructural pathology, microbiology, and virology. The division also offers services in response to national and international requests for consultation on childhood disorders; pediatric solid organ neoplasia, including pediatric bone and soft tissue tumors; transplantation pathology involving the liver, bowel, kidney, lung, heart, and bone marrow; post-transplant lymphoproliferative disorders; bowel motility disorders, including acetylcholinesterase staining for the diagnosis of Hirschsprung’s disease; histiocyte disorders, including Langerhans cell histiocytosis and dendritic cell disorders; and molecular diagnostics for pediatric infectious disease, including pertussis and quantitative EpsteinBarr virus analysis. Pathology at the VA Pittsburgh Healthcare System Mona F. Melhem, M.D. Director

The Division of Pathology at the VA Pittsburgh Healthcare System provides comprehensive pathology and laboratory medical services to three area VA centers and provides consultation services to a fourth center in Butler County. Its specialized services include flow cytometry for hematopathology, immunohistochemistry for histology, therapeutic drug monitoring for clinical chemistry, and Legionella epidemiology for microbiology. This division serves as an immunopathology reference laboratory and supports VA Pittsburgh Healthcare System special patient care programs like open heart surgery and liver transplantation.

Pathology at UPMC Shadyside Rajiv Dhir, M.B.B.S. Acting Director

The Division of Pathology at UPMC Shadyside provides a complete spectrum of care, including sophisticated services in oncology, urology, cardiology, and geriatrics at both UPMC Shadyside and UPMC Presbyterian. Some division faculty members hold expertise in urologic and prostate pathology, areas not included in other divisions. Centers of excellence include genitourinary pathology, pathology informatics, gastrointestinal pathology, outcomes research, and dermatopathology. This division is the center for analysis of all diagnostic material generated by the department’s efforts to incorporate gene array analysis as a diagnostic tool. Other Divisions Community Pathology Samuel A. Yousem, M.D. Director

The Division of Community Pathology integrates laboratory and pathology services at these UPMC community hospitals: Horizon, South Side, St. Margaret, Bedford Memorial, McKeesport, and Passavant. This collaboration helps these hospitals, which might otherwise have difficulty maintaining comprehensive pathology services, to provide all sophisticated laboratory testing required for modern practice and have access to intellectual resources through consultation with faculty members in the department. Pathology Informatics Anil K. Parwani, M.D., Ph.D. Director

The Division of Pathology Informatics maintains and develops clinical information systems to support anatomic pathology, clinical pathology, and molecular diagnostics. It conducts research programs focused on the

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next generation of pathology reporting methods, imagery, and bioinformatics. Initiatives include developing Internet-based telepathology consultations, supporting UPMC’s multimedia electronic medical record effort, and developing state-of-the-art systems for patient reporting over the Web.

levels of the protein beta-catenin, the overexpression of which is linked to tumor development. Together, these findings indicate that omega-3 fatty acids can work on several levels to inhibit liver cancer growth. Wu and colleagues plan to move their findings into a mouse model of hepatocellular carcinoma.

causing cell damage instead of stimulating regeneration. Zarnegar has determined that cMet-Fas dimerization is due to a common sequence between cMet and the Fas ligand that he has isolated and is now moving toward the drug discovery research pathway. Alan Wells, M.D., D.Med.Sci., and

Jianhua Luo, M.D., Ph.D., and

Cellular and Molecular Pathology George K. Michalopoulos, M.D., Ph.D. Director

The Division of Cellular and Molecular Pathology conducts research in tissue biology and disease pathogenesis, using techniques from cellular and molecular biology to investigate normal and abnormal tissue growth and differentiation, mechanisms of immunity, pathways leading to disease, and markers of molecular diagnosis. Faculty members’ research specifically includes hepatic biology, pulmonary biology, renal biology, prostate cancer, growth factors in the nervous system, bone growth and regulation, matrix effects in complex tissue growth, and gene expression and genomic alterations in human cancer. Selected Research Highlights Tong Wu, M.D., Ph.D., and colleagues

have determined that omega-3 fatty acids—found in fish oil, seeds, and nuts—inhibit the growth of hepatocellular carcinoma, which accounts for 80 to 90 percent of all liver cancers and is normally fatal within three to six months of diagnosis. The team exposed hepatocellular carcinoma cells to the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) for 12 to 48 hours and found that the agents inhibited cell growth. In addition, DHA and EPA were shown to cleave poly(ADP-Ribose) polymerase (PARP), a process indicative of apoptosis, thereby promoting the elimination of tumor cells. The omega-3 fatty acids also decreased

colleagues use high throughput quantitative analysis to genetically profile prostate cancer tissue. The team has identified 671 genes whose expression levels are significantly altered in prostate cancer tissue compared to disease-free tissue. Interestingly, the researchers investigated the profile of benign tissue directly adjacent to prostate cancer tissue and found gene expression in the benign tissue to be much more similar to the cancerous tissue than to disease-free tissue. Luo noted that the genetic alteration in adjacent benign tissue represented a field effect, indicating genetic changes similar to prostate cancer in morphologically benign tissue. The expression pattern can be used to predict the tumor’s aggressiveness, with an 80 percent success rate. Because only a fraction of prostate cancers are metastatic, using this technique to predict the aggressive, or metastatic, nature of the cancer would aid clinicians in planning treatment strategies. Hypoxia, or oxygen depletion, arises during a variety of physiological states, including ischemia, respiratory diseases, and tumorigenesis. It can also lead to cell death just prior to reoxygenation due either to tissue damage (necrosis) or apoptosis. Reza Zarnegar, Ph.D., examines growth regulation in hepatocytes and has found that the human growth factor (HGF) receptor cMet forms a dimer with the apoptotic receptor Fas, preventing Fas from trimerizing and inducing cell death. However, high levels of HGF, like those that occur in fulminant hepatits, may actually induce apoptosis, thereby

colleagues study cell migration in terms of how motility processes are regulated and play a role in physiologic and pathologic situations like wound healing and tumor invasion. Cell motility is a complex process involving a series of asymmetrical events, including lamellipodium extension, leading-edge adhesion formation, rear detachment, and cell body contraction, all of which must coordinate for successful cell movement. To establish a model system, Wells and colleagues explore motility signaling from the epidermal growth factor receptor (EGFR), which functions centrally for a wide variety of stromal and epithelial tissues. Results have shown that m-calpain, a factor activated by EGF when adjacent to the cell membrane, produces the cell body and rear deadhesion required for cellular locomotion. In addition , m-calpain appears to be localized only in nonlamellipodial regions, confirming that it is key in cell-releasing regions, allowing lamellipodia to adhere in new locations and move the cell in a single direction. Tim D. Oury, M.D., Ph.D., and his

laboratory are focused on understanding the molecular mechanisms involved in pulmonary fibrosis and acute interstitial lung disease. The group is investigating the role of extracellular oxidants in mediating physiologic and pathologic responses and has found that the enzyme extracellular superoxide dismutase (ECSOD) can protect against pulmonary fibrosis and prevent inflammatory responses in the lung. Oury and his team are investigating mechanisms

by which EC-SOD mediates inflammatory lung responses and have determined that EC-SOD is released directly from inflammatory cells rather than migrating from lung parenchyma, as previously believed. In addition, the team has determined, in studies using knockout mice, that an absence of EC-SOD increases oxidative stress and injury to the lung, especially following exposure to asbestos.

Center Center for Pathology Informatics Anil K. Parwani, M.D., Ph.D. Director

Regular Faculty Endowed Chairs A.J. Demetris, M.D. Thomas E. Starzl Professor of Transplantation Pathology

Ronald Jaffe, M.B.B.Ch. Marjory K. Harmer Professor of Pediatric Pathology George K. Michalopoulos, M.D., Ph.D. Maud L. Menten Professor and Chair Alan Wells, M.D., D.Med.Sci. Thomas J. Gill III Professor of Clinical Pathology Clayton A. Wiley, M.D., Ph.D. Pathology Education and Research Foundation Professor Professors Antonio J. Amortegui, M.D. Robert Marshall Austin, M.D., Ph.D. Leon Barnes Jr., M.D. Dorothea Becker, Ph.D. Harry C. Blair, M.D. Yuan Chang, M.D. David J. Dabbs, M.D. Albert B. DeLeo, Ph.D. Rene J. Duquesnoy, Ph.D. Elieser S. Gorelik, M.D., Ph.D. Miroslawa W. Jones, M.D. Anisa I. Kanbour, M.D. Amal I. Kanbour-Shakir, M.D., Ph.D. Jeffrey A. Kant, M.D., Ph.D. Youhua Liu, Ph.D. Trevor A. Macpherson, M.D.

Mona F. Melhem, M.D. Michael A. Nalesnik, M.D. Yuri Nikiforov, M.D., Ph.D. Stephen S. Raab, M.D. Bruce S. Rabin, M.D., Ph.D. Parmjeet S. Randhawa, M.D. Uma N.M. Rao, M.B.B.S. Charles R. Rinaldo Jr., Ph.D. Stephen C. Strom, Ph.D. Steven H. Swerdlow, M.D. Darrell J. Triulzi, M.D. Mohamed A. Virji, M.D., Ph.D. Robert M. Wadowsky, Sc.D. Theresa L. Whiteside, Ph.D. Chuanyue Wu, Ph.D. Samuel A. Yousem, M.D. Reza Zarnegar, Ph.D. Adriana Zeevi, Ph.D. Associate Professors Rajnikant M. Amin, M.B.B.S. Andrew A. Amoscato, Ph.D. Sheldon I. Bastacky, M.D. Gary E. Blank, Ph.D. Robert P. Bowser, Ph.D. Gloria Jean Carter, M.D. Shiyuan Cheng, Ph.D. Charleen T. Chu, M.D., Ph.D. Lydia C. Contis, M.D. Fiona E. Craig, M.B.B.S. Rajiv Dhir, M.B.B.S. Roy A. Frye, M.D., Ph.D. Ronald L. Hamilton, M.D. Frank J. Jenkins, Ph.D. Jeanne A. Jordan, Ph.D. Sikandar L. Katyal, Ph.D. Shih-Fan Kuan, M.D., Ph.D. William A LaFramboise, Ph.D. Eric Lagasse, Ph.D. Luyuan Li, Ph.D. Jianhua Luo, M.D., Ph.D. Wendy M. Mars, Ph.D. Geoffrey Howard Murdoch, M.D., Ph.D. N. Paul Ohori, M.D. Zoltan N. Oltvai, M.D. Tim D. Oury, M.D., Ph.D. Alka S. Palekar, M.D. A. William Pasculle, Sc.D. Robert L. Peel, M.D. Hanna Rabinowich, Ph.D. Gutti R. Rao, M.D. Michael R. Shurin, M.D., Ph.D. Urvashi S. Surti, Ph.D. Lisa Anne Teot, M.D. Giuliana A. Trucco, M.D. Tong Wu, M.D., Ph.D. Xiao-Ming Yin, M.D., Ph.D.

Visiting Associate Professors Raymond E. Felgar, M.D., Ph.D. Walid E. Khalbuss, M.D., Ph.D. William A. Parks Jr., M.D. Anupama Sharma, M.B.B.S. Research Associate Professors Joseph T. Newsome, D.V.M. Nikola Vujanovic, M.D., Ph.D. Assistant Professors Evan E. Baker, M.D. Rohit Bhargava, M.D. Guoping Cai, M.D. Irina Yefimovna Chibisov, M.D. Mamatha Chivukula, M.B.B.S. Laure Pascale Croisille, M.D., Ph.D. Sanja Dacic, M.D., Ph.D. Jon M. Davison, M.D. Marie Colette Defrances, M.D., Ph.D. Miroslav S. Djokic, M.D. Maryann A. Donovan, Ph.D. Jeffrey Louis Fine, M.D. Csaba Galambos, M.D. Christine F. Garcia, M.D. Nick Giannoukakis, Ph.D. Alin Lucian Girnita, M.D. Nadia Fouad Habib-Bien, M.B.B.Ch., Ph.D. Donald L. Kelley, M.D. Lawrence P. Kiss, M.D. Alyssa M. Krasinskas, M.D. Matthew D. Krasowski, M.D., Ph.D. Scott M. Kulich, M.D. Bo Liu, Ph.D. Kathryn Alicia McFadden, M.D., Ph.D. Sara Antoinette Monaghan, M.D. Satdarshan P.S. Monga, M.B.B.S. Olga Navolotskaia, M.D. Lawrence C. Nichols, M.D. Marina Nikiforova, M.D. Erin Rubin Ochoa, M.D. Scott R. Owens, M.D. John A. Ozolek, M.D. Anil K. Parwani, M.D., Ph.D. Sureshchandra Patel, M.B.B.S. Lina P. Perry, M.D. Lirong Qu, M.D., Ph.D. Sarangarajan Ranganathan, M.B.B.S. Lisa Jeannine Robinson, M.D. Anna Marie Roman, Ph.D. Karen E. Schoedel, M.D. Raja Ram Seethala, M.D. Jorge Sepulveda, M.D., Ph.D. Jagjit Singh, M.B.B.S. Manjit K. Singh, Ph.D. Minh-Ha Tran, D.O. Mark Harris Yazer, M.D. Jian Yu, Ph.D. Yanping Yu, M.D., Ph.D. Chengquan Zhao, M.D.

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David H. Perlmutter, M.D., Vira I. Heinz Professor and Chair

Research Assistant Professors Aaron W. Bell, Ph.D. Richard J. Bodnar, Ph.D. Chunsun Dai, M.D., Ph.D. Wen-Xing Ding, Ph.D. Anette Ute Duensing, M.D. Vijayalakshmi C. Gandhi, Ph.D. Chang Han, M.D., Ph.D. David Malehorn, Ph.D. Galina V. Shurin, Ph.D. Yongjun Zhang, Ph.D. Instructor Christine Odoux, Ph.D. Visiting Instructor Eizaburo Sasatomi, M.D. Research Instructors Wentao Gao, M.D., Ph.D. Lisheng Ge, Ph.D. Leslie A. Goldstein, Ph.D. Jie Han, M.D., Ph.D.

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DEPARTMENT PROFILE

The mission of the Department of Pediatrics is to provide the best medical care for children and to advance knowledge about the pathogenesis, diagnosis, prevention, and treatment of pediatric diseases. The department’s wide-ranging program encompasses 19 divisions: Adolescent Medicine; Infectious Diseases; Cardiology; Child Advocacy and Injury Prevention; Developmental-Behavioral Pediatrics; Diagnostic Referral Service; Pediatric Emergency Medicine; Endocrinology; General Academic Pediatrics; Hematology/Oncology; Immunogenetics; Medical Genetics; Neonatology and Developmental Biology; Child Neurology; Nephrology; Pediatric Gastroenterology; Pulmonology, Allergy, and Immunology; Rheumatology; and Weight Management and Wellness.

Residency and Training Programs

The Department of Pediatrics offers three residency training programs: categorical pediatric residency; medicine-pediatric residency; and a triple board residency covering pediatrics, psychiatry, and child psychiatry. The department also offers fellowship programs in the following 16 areas: adolescent medicine, allergy/ immunology, pediatric infectious diseases, pediatric cardiology, pediatric emergency medicine, pediatric endocrinology, pediatric gastroenterology, general academic pediatrics, hematology/oncology, medical genetics, neonatology and developmental biology, nephrology, pediatric epilepsy, pulmonology, pediatric rheumatology, and developmental/behavioral pediatrics. Divisions Adolescent Medicine Pamela J. Murray, M.D., M.H.P. Chief

The Division of Adolescent Medicine provides diagnostic and treatment services for young adults 12 to 21 years old in an age-appropriate setting. Care is provided for general medical problems as well as those particular to the adolescent years like growth and development, puberty, sexual health care (including gynecological pediatrics and sexually transmitted diseases), smoking cessation, substance abuse, eating disorders, and family planning. The division creates

and distributes information to health care providers on common adolescent diseases and conditions, new approaches to treatment, best practices and standards of health care for adolescents, health outcomes, and models of service delivery. Infectious Diseases Toni Darville, M.D. Chief

The Division of Infectious Diseases focuses on patients with various infectious diseases as well as suspected or known immunodeficiencies. The division’s clinical consultation service works closely with physicians providing transplant services and caring for patients exposed to or infected with human immunodeficiency virus. Research in the division includes evaluation of novel childhood vaccines, including vaccines for otitis media and influenza. Researchers are also investigating streptococcus, tuberculosis, and transplant-related infections. Cardiology Steven A. Webber, M.B.Ch.B. Chief

The Division of Cardiology provides comprehensive clinical services from birth through adulthood for patients with congenital and acquired heart diseases. The clinical program includes ambulatory diagnostic services, a

fetal cardiology program, diagnostic and interventional cardiac catheterization, medical management of cardiac dysrhythmias, inflammatory diseases, heart failure, surgical management of congenital cardiovascular malformations, and a dedicated pediatric cardiac intensive care unit. The division’s clinical research program focuses on optimizing outcomes following pediatric heart and heart-lung transplantation and during the management of congenital heart diseases. Basic science research focuses on the physiology and biomechanics of developing cardiovascular systems, with an emphasis on the mechanisms responsible for congenital cardiac malformations. Child Advocacy and Injury Prevention Janet E. Squires, M.D. Chief

The Division of Child Advocacy and Injury Prevention provides medical and social evaluations of children suspected of being abused; develops community service, outreach, and education programs designed to prevent abuse; and serves an advocacy role for children and families in the legal system because of abuse. The division provides primary care and assessments for children in foster care as well as those in preadoptive and adoptive care. It also identifies ongoing developmental and behavioral problems in children who have been maltreated or neglected. Division research focuses on biochemical, biomechanical, and biomedical factors that allow earlier identification of an abused child and, therefore, intervention and treatment as early as possible.

Developmental– Behavioral Pediatrics Robert B. Noll, Ph.D. Chief

The Division of DevelopmentalBehavioral Pediatrics provides care for children with developmental and/or behavioral problems, children at risk for such problems, and their families. The division generates and disseminates new knowledge about the prevention, identification, etiology, impact, and treatment of developmental and behavioral problems. Faculty members collaborate with community agencies and programs to improve services for these children and their families. Division research focuses on language development in various developmental disorders, autism, disability prevention through early prenatal care and education, and coping mechanisms for chronic disease. Paul C. Gaffney Diagnostic Referral Service Basil J. Zitelli, M.D. Chief

The Paul C. Gaffney Diagnostic Referral Service handles some of the most difficult and challenging pediatric patients, including those with multi-system diseases that do not fit into a single subspecialty category and require specialized coordination of their care. In addition, the division provides rapid access to various subspecialty services for complex medical conditions. Pediatric Emergency Medicine Richard A. Saladino, M.D. Chief

The Division of Pediatric Emergency Medicine treats children with acute illnesses and injuries through the emergency department at Children’s Hospital of Pittsburgh of UPMC. Research in the division focuses on capnometry (the measurement of end-tidal CO2 ), bronchoconstriction,

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occult life-threatening problems, resuscitation, physiologic effects of drugs used for sedation and rapidsequence endotracheal intubation, childhood injury prevention, effects of maternal depression on children’s health, biomechanics of traumatic injury, common infectious diseases in outpatient settings, childhood respiratory problems, forensic pediatrics, and development of Internet-based health records for children. Endocrinology Dorothy J. Becker, M.B.B.Ch. Chief

Clinical services provided by the Division of Endocrinology include consultations, endocrine testing, and education concerning diabetes and nutrition for patients and their families. Division research focuses on diabetes, polycystic ovary syndrome, genetic abnormalities, pubertyrelated development and disorders, and endocrine modulation by environmental factors. General Academic Pediatrics Alejandro Hoberman, M.D. Chief

The Division of General Academic Pediatrics provides family-centered primary health care for infants, children, and adolescents. The division develops and disseminates new information about common childhood diseases and conditions, new approaches to treatment, best practices and standards of care, health outcomes, models of service delivery, and related issues. Comprehensive health care services in the division include regular checkups and immunizations, care for unexpected injury or illness, and special services like a question call-in line and emergency care. Current research focuses on otitis media and urinary tract infections.

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Hematology / Oncology A. Kim Ritchey, M.D. Chief

Medical Genetics Gerard Vockley, M.D., Ph.D. Chief

The Division of Hematology/ Oncology cares for children with blood diseases and cancers using teams of clinical specialists in general oncology, neuro-oncology, sickle cell disease, coagulation, and stem cell transplantation. The division’s clinical research includes studies as part of the Children’s Oncology Group, a nationwide clinical trials program conducting trials in stem cell transplantation as well as treatment of sickle cell disease and aplastic anemia. Basic research in the division investigates stem cell biology and molecular oncology.

Among its clinical services, the Division of Medical Genetics provides evaluation of children with disorders that result from genetic diseases and/or birth defects and engages the necessary specialists and support to optimize their physical treatment and mental health. Research in the division includes studies of the molecular basis of mitochondrial fatty acid oxidation defects.

Immunogenetics Massimo M. Trucco, M.D. Chief

The Division of Immunogenetics provides basic science support aimed at more efficiently and correctly diagnosing, treating, and possibly preventing children’s diseases. One of the division’s main interests is pediatric diabetes. Faculty members work with the University of Pittsburgh Diabetes Institute to study the etiopathogenesis of type 1 diabetes, explore possible ways to prevent the disease in genetically predisposed children, predict who will eventually convert to the disease, and investigate therapeutic approaches that are more appropriate and feasible than daily injections of recombinant insulin. Among the institute’s research goals are to generate new and more abundant insulin-secreting cells, to protect islet cells before transplanting them into recipients, and to develop recipient tolerance of donor cells to avoid the need for immunosuppressive drugs.

Neonatology and Developmental Biology Gary A. Silverman, M.D., Ph.D. Chief

The Division of Neonatology and Developmental Biology provides care for high-risk neonates in the neonatal intensive care units (NICUs) at Magee-Womens Hospital of UPMC and Children’s Hospital of Pittsburgh of UPMC. Clinical activities include consultations for high-risk obstetric patients, delivery room resuscitative support, and NICU care, which encompasses care for cardiac, neurosurgical, urological, genetic, and other complex medical problems. The division’s research program focuses on developmental lung biology, pathobiology of neonatal hyperbilirubinemia and kernicterus, developmental pharmacology, neonatal growth and nutrition, retinopathy of prematurity, prenatal brain metabolism and injury, mechanisms of pre-term labor, and efforts to improve muscle function via gene therapy. Child Neurology Ira Bergman, M.D. Chief

The Division of Child Neurology provides care for children with disorders of the central and peripheral nervous systems. One focus of the division’s clinical care is epilepsy, including a comprehensive program with pharmacological, neuroimaging,

dietary (ketogenic diet), communication, and psychiatric services. The division participates in clinical trials for new anti-epileptic drugs. Division research focuses on genetic leukodystrophies, tumor immunotherapies and chemotherapy, anti-epileptic drugs, central nervous system development, and muscular dystrophy. Nephrology Demetrius Ellis, M.D. Chief

The Division of Nephrology provides care and consultation for children with renal disorders, including electrolyte disturbances, hematuria, proteinuria, glomerulonephritis, urinary tract inflections, end-stage renal disease, and pediatric hypertension. Clinical activities include acute and chronic dialysis, kidney transplantation for infants and children, and treatment for pediatric hypertension and acquired glomerular disorders. Research in the division includes disorders of sodium and water metabolism (central pontine myelinolysis, hyponatremic encephalopathy, and hypernatremic dehydration), the genetic basis of nephrotic syndrome, viral infection after renal transplantation, and hemodialysis for children. Pediatric Gastroenterology Mark E. Lowe, M.D., Ph.D. Chief

The Division of Pediatric Gastroenterology provides care and consultation for children with a variety of conditions, including abdominal pain, gastroesophageal reflux and esophagitis, eosinophilic disorders, gastrointestinal bleeding, ulcer disease, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), diarrhea, poor growth, feeding disorders, intestinal failure (short-bowel), motility disorders, constipation, irritable bowel syndrome,

liver diseases, liver transplantation, small bowel transplantation, acute and chronic pancreatitis, and metabolic disorders affecting the liver or intestines. Research in the division focuses on metabolic liver disease, pancreatitis, molecular regulation of fat digestion and satiety, inflammatory bowel disease, and cystic fibrosis transmembrane conductance regulation in the small intestine. Pulmonology, Allergy, and Immunology Jay K. Kolls, M.D. Chief

The Division of Pulmonology, Allergy, and Immunology cares for children with acute or chronic pulmonary disorders, cystic fibrosis, airway lesions, sleep disorders, allergic rhinitis, atopic dermatitis, drug allergies, insect hypersensitivity, uticaria, and angioedema. The division provides clinical consultation for patients with asthma, recurrent pneumonia, bronchopulmonary dysplasia, neuromuscular disorders, airway lesions, immunodeficiencies, and other lung diseases in addition to a comprehensive sleep program for children. Division research focuses on the molecular basis of host defense at the respiratory epithelium, pathogenesis of bacterial pneumonia, cystic fibrosis, exercise physiology and respiration, environmental airway irritants, muscular dystrophy, and lung transplantation. Rheumatology Raphael Hirsch, M.D. Chief

The Division of Rheumatology provides care for children with musculoskeletal and autoimmune diseases, the most common of which is juvenile rheumatoid arthritis. The division’s team of physicians also provides care and consultation for other conditions, including joint and muscle pain, systemic lupus erythematosus, dermatomyositis, vasculitis,

uveitis, Raynaud’s disease, Kawasaki disease, scleroderma, and fibromyalgia. Research efforts include collaboration on clinical trials for a novel juvenile rheumatoid arthritis drug, including evaluation of patients’ quality of life. Basic research in the division focuses on T-cell function in autoimmunity and the biology of gene transfer. Weight Management and Wellness Silva A. Arslanian, M.D. Chief

The Weight Management and Wellness Division cares for children with obesity and its complications. Treatment protocols include behavioral, exercise, and surgical approaches. Division research focuses on pathobiology of obesity-related complications as well as methods for predicting and preventing these complications. Selected Research Highlights Massimo M. Trucco, M.D., and

colleagues have developed a method to reverse juvenile diabetes in an animal model of the disease. Type 1 diabetes, which typically begins in childhood, is believed to occur when T cells in the body’s immune system interact with and destroy the insulinproducing beta cells of the pancreas. Using a mouse model, Trucco and his team modified the dendritic cells, thus inhibiting T-cell interactions with beta cells and giving the beta cells a chance to regenerate and resume insulin production. Halting the immune system’s destruction of pancreatic beta cells enabled the team to eliminate type 1 diabetes in the mouse model. By using a patient’s own cells, this technique would eliminate the need for immune responsive therapies. The Food and Drug Administration has approved a clinical trial that is expected to enroll at least 15 patients over the age of 18 with type 1 diabetes.

Inflicted traumatic brain injury (iTBI), a result of abuse, is the leading cause of TBI death in infants. Misdiagnosis of iTBI is common because children often exhibit nonspecific symptoms like vomiting and fussiness, and a physical exam can be normal. Rachel P. Berger, M.D., M.P.H., and colleagues are investigating biomarkers that may be able to assist in screening infants who are at high risk for iTBI and whose injury might otherwise be missed. A prospective case-control study was conducted of 98 well-appearing infants who presented with nonspecific symptoms and no history of trauma. The researchers found that serum and/or cerebral spinal fluid (CSF) concentrations of neuron-specific enolase (NSE) and myelin basic protein (MBP) may be useful for screening infants who are at increased risk for iTBI and who may benefit from additional evaluation with a head computed tomography scan. The ability to identify iTBI that might otherwise be missed has important implications for decreasing morbidity and mortality from iTBI. Robert H. Squires Jr., M.D., and

colleagues conducted a prospective, multicenter case study collecting demographic, clinical, laboratory, and short-term outcome data on children from birth to 18 years with acute liver failure (ALF). Three weeks into the study, patients were evaluated for primary outcome measures, which included death, death after transplantation, alive with native liver, and alive with transplanted organ. The researchers determined that ALF causes in children included acute acetaminophen toxicity (14 percent), metabolic disease (10 percent), autoimmune liver disease (6 percent), non-acetaminophen drug-related hepatotoxicity (5 percent), infections (6 percent), and other diagnosed conditions (10 percent). Nearly half (49 percent)

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of the causes were indeterminate. Outcomes varied among patient subgroups. Squires and colleagues determined that the causes of ALF in children differ from those in adults and noted that the high percentage of indeterminate cases warrants further investigation. Children’s developmental impairments have often been attributed to persistent middle-ear effusion in early life. Jack L. Paradise, M.D., and colleagues previously reported that among children younger than 3 with persistent middle-ear effusion, prompt insertion of tympanostomy tubes did not result in improved cognitive, language, speech, or psychosocial development at 3, 4, or 6 years of age. However, developmental comparisons had not been made at later ages. Paradise and colleagues enrolled 6,350 infants soon after birth and evaluated them regularly for middle-ear effusion. Before age 3, 429 children with persistent effusion were randomly assigned to have tympanostomy tubes inserted promptly or up to nine months later if effusion persisted. Literacy, attention, social skills, and academic achievement were assessed in 391 of these children at 9 to 11 years of age. Results indicated that developmental scores in the early tympanostomy group did not differ significantly from scores in the group that underwent delayed insertion. The researchers concluded that in otherwise healthy young children with persistent middle-ear effusion, prompt insertion of tympanostomy tubes does not improve developmental outcomes up to 11 years of age.

Depletion or dysfunction of CD4+ T lymphocytes greatly disrupts host defenses and impairs vaccine immunogenicity. Mingquan Zheng, M.D., Chad Steele, Ph.D., and Jay K. Kolls, M.D., have shown that plasmid DNA vaccination with a cassette encoding the antigen and a second cassette encoding a full-length CD40 ligand (CD40L), a molecule critical for T cell helper function, can elicit significant titers of antigen-specific immunoglobulins in serum and CD8+ T cell responses in CD4deficient mice. The research team investigated whether this approach could lead to CD4+ T cellindependent vaccine protection against a prototypic AIDS-defining infection, Pneumocystis (PC) pneumonia. Zheng and colleagues used serum from mice vaccinated with PC-pulsed, CD40L-modified dendritic cells to immunoprecipitate PC antigens. They identified the antigen Kexin and used it in a similar DNA vaccine strategy, with or without CD40L pairing. CD4-deficient mice receiving DNA vaccines encoding both Kexin and CD40L showed significantly higher anti-PC immunoglobulin titers and a 3-log greater protection in a PC challenge model compared to Kexin alone. The results show promise for development of CD4-independent vaccination against HIV-related or other opportunistic pathogens.

Center Pediatric Clinical and Translational Research Center Silva A. Arslanian, M.D. Director

Regular Faculty Endowed Chairs Silva A. Arslanian, M.D. UPMC Richard L. Day Professor

Raphael Hirsch, M.D. Aldo V. Londino Jr., M.D., Professor Alejandro Hoberman, M.D. Jack L. Paradise Professor of Research Jay K. Kolls, M.D. UPMC Niels Jerne Professor David M. Orenstein, M.D. Antonio J. and Janet Palumbo Professor of Cystic Fibrosis David H. Perlmutter, M.D. Vira I. Heinz Professor and Chair Edward V. Prochownik, M.D., Ph.D. Paul C. Gaffney Professor of Pediatric Hematology Massimo M. Trucco, M.D. Hillman Professor of Pediatric Immunology Basil J. Zitelli, M.D. Edmund R. McCluskey Professor of Pediatric Education Carol Ann Craumer Chair in Pediatric Research (open) Ronald L. and Patricia M. Violi Chair in Child Development (open) Professors Stephen J. Bagnato Jr., Ph.D. Dorothy J. Becker, M.B.B.Ch. Lee B. Beerman, M.D. Ira Bergman, M.D. Mananda S. Bhende, M.D. Beverly S. Brozanski, M.D. William I. Cohen, M.D. Patricia K. Crumrine, M.D. Demetrius Ellis, M.D. David N. Finegold, M.D. Michael D. Green, M.D.

Dena S. Hofkosh, M.D. Phillip H. Kaleida, M.D. David J. Keljo, M.D. Bradley B. Keller, M.D. Geoffrey Kurland, M.D. Mark E. Lowe, M.D., Ph.D. Sara C. McIntire, M.D. Marian G. Michaels, M.D. Robert B. Noll, Ph.D. Salvatore J. Orlando, M.D. Sang C. Park, M.D. A. Kim Ritchey, M.D. Frederick S. Sherman, M.D. Gary A. Silverman, M.D., Ph.D. Mark A. Sperling, M.D. Janet E. Squires, M.D. Robert H. Squires Jr., M.D. Andrew H. Urbach, M.D. Gerard Vockley, M.D., Ph.D. Jon F. Watchko, M.D. Steven A. Webber, M.B.Ch.B. Michael R. Wollman, M.D. Visiting Professors Toni Darville, M.D. Luigi R. Garibaldi, M.D. Kenneth M. Gibson, Ph.D. Robert David Nicholls, D.Phil. Bruno M. Peault, Ph.D. Benjamin Leighton Shneider, M.D. Associate Professors Michael J. Balsan, M.D. Charles V. Bender, M.D. Barbara Ann Cohlan, M.D. Curt G. DeGroff, M.D. Abbe Niccolo De Vallejo, Ph.D. Jonathan D. Finder, M.D. Melanie A. Gold, D.O. Rakesh K. Goyal, M.D. Sara C. Hamel, M.D. Robert W. Hickey, M.D. Regina I. Jakacki, M.D. Denise G. Karasic, D.O. Raymond B. Karasic, M.D. Lakshmanan Krishnamurti, M.D. Judith M. Martin, M.D. Francis Michael McCaffrey, M.D. Michael L. Moritz, M.D. Pamela J. Murray, M.D., M.H.P. Raymond Pitetti, M.D. Eric S. Quivers, M.D. Goutham Rao, M.D. Evelyn C. Reis, M.D. Richard A. Saladino, M.D. Abhay N. Vats, M.D. Selma F. Witchel, M.D.

Visiting Associate Professors Stacey Drant Allada, M.D. Vivekanand Allada, M.D. Karen Russell Schmidt, M.D. Shelley Dianne Williams, M.D. Research Associate Professors Frank Yongzhong Chen, Ph.D. William A. Rudert, M.D., Ph.D. Assistant Professors Feras Tawfiq Alissa, M.B.B.S. Gulay Alper, M.D. Nadia A. Ameen, M.B.B.S. Thaschawee Arkachaisri, M.D. Gauurav Arora, M.D. Miya R. Asato, M.D. Fida Farouk Bacha, M.D. Rachel P. Berger, M.D., M.P.H. Cheryl Lynn Blank, D.O. Debra L. Bogen, M.D. Benjamin S. Bolser, M.D. Leslie Mary Borsett-Kanter, M.D. Rita Bottino, Ph.D. Carol Lynn Cabral, M.D. Sangeeta Chakravorty, M.B.B.S. Jennifer Marie Chianese, M.D. Sylvia S.Y. Choi, M.D. Constantinos Chrysostomou, M.D. Maria I. Clavell, M.D. Lee Ann E. Conard, D.O. Michael James Decker, M.D. Ingrid M. Libman DeGordon, M.D., Ph.D. Hengjiang Dong, Ph.D. Johanna Lynn Drickman, M.D. Patricia J. Dubin, M.D. Suzanne Elizabeth Dvergsten, M.D. Elif Erkan, M.D. Oscar Escobar, M.D. Orooj Fatima Fasiuddin, M.D. Brian D. Feingold, M.D. Susan Hetzel Frangiskakis, M.D. Sylvia E. Garcia, M.D. Kara Lisa Gardner, M.D. Satyanarayana Gedela, M.B.B.S. Elissa Baker Gittes, M.D. Eric S. Goetzman, Ph.D. Alka Goyal, M.D. Todd David Green, M.D. Sriya W. Gunawardena, M.B.B.S. Kristin M. Hannibal, M.D. Tamara S. Hannon, M.D. Monique Higginbotham, M.D. Amber M. Hoffman, M.D. Deborah Lee Holder, M.D. Cynthia R. Johnson, Ph.D. Daniel A. Kietz, M.D. Janet M. Kinnane, M.D.

Jennifer L. Kloesz, M.D. Jacqueline Kreutzer, M.D. Sanjay Lambore, M.B.B.S. SoJung Lee, Ph.D. Christina M. Lehane, M.D. Rhett Howard Lieberman, M.D. Philana L. Lin, M.D. Douglas Scott Lindblad, M.D. Andrew James MacGinnitie, M.D., Ph.D. Suneeta Madan, M.B.B.S. Purushothaman Madhu, M.D. Burhanuddin Mahmood, M.B.B.S. Clayton E. Mathews, Ph.D. Carla Ann Mazefsky, Ph.D. William J. McCarran, M.D. Katie Elizabeth McPeak, M.D. Susan A. Miller, M.D. Deborah R. Moss, M.D. Timothy D. Murphy, M.D. David R. Nash, M.D. Andrew John Nowalk, M.D., Ph.D. Laura Michelle Panko, M.D. Erin Doherty Phrampus, M.D. Jon D. Piganelli, Ph.D. Derek A. Pociask, Ph.D. Kumaravel Rajakumar, M.B.B.S. John Carter Ralphe, M.D. Dana L. Rofey, Ph.D. Paul Rosen, M.D. Margalit Elana Rosenkranz, M.D. Kimberly R. Roth, M.D. Linda Marie Russo, M.D. Robert A. Safier, M.D. Nader Shaikh, M.D., M.P.H. Peter H. Shaw, M.D. Diana Alexandra Shellmer, Ph.D. Sonia Singh, M.B.B.S., M.P.H. Jonathan E. Spahr, M.D. Gina Suzanne Sucato, M.D., M.P.H. Agnieszka Swiatecka-Urban, M.D. Jean M. Tersak, M.D. Inna I. Vaisleib, M.D. Kalyani Rai Vats, M.B.B.S. Kishore Vellody, M.D. Yatin Mahendra Vyas, M.B.B.S., M.D. Daniel Jerome Weiner, M.D. Toby D. Yanowitz, M.D. Noel Spears Zuckerbraun, M.D. Visiting Assistant Professors Hoda Zakaria Abdel-Hamid, M.B.B.S. James L. Kreindler, M.D. Catherine Mary O’Connell, Ph.D.

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Bruce A. Freeman, Ph.D., UPMC Irwin Fridovich Professor and Chair

Research Assistant Professors David Jonathan Askew, Ph.D. Suzanne Bertera, Ph.D. Elizabeth Hager Cothren, Ph.D. Yanhua Gao, M.D., Ph.D. Jing He, M.D., Ph.D. Tunde Hidvegi, Ph.D. Clifford James Luke, Ph.D. Patrizia Luppi, M.D. Terence Francis McGuire, Ph.D. Stephanie Jean Mihalik, Ph.D. Al-Walid A. Mohsen, Ph.D. Stephen Chongoh Pak, Ph.D. Steven M. Ringquist, Ph.D. Mihaela Stefan, Ph.D. Kimimasa Tobita, M.D. Tatyana V. Votyakova, Ph.D. Xuejun Zhao, M.D. Mingquan Zheng, M.D. Instructors Shean J. Aujla, M.D. Mary E. Brown, M.D. Debra Ellenberger Cohen, M.D. Reed William Van Deusen, M.D. Research Instructors Dianna L. Ploof, Ed.D. Bin Sun, Ph.D. Yudong Wang, Ph.D.

PHARMACOLOGY

DEPARTMENT PROFILE

The Department of Pharmacology sees its mission as educating medical students and physicians in the rational use of drugs; training basic and clinical pharmacologists; developing new knowledge concerning therapeutically useful substances; and providing drug information and consultation services as needed. Pharmacology is a basic science with strong clinical ties so pharmaceutical principles can be taught within the context of specific bodily functions. At the same time, the department maintains a program of interactive and interdisciplinary research with a focus on cellular communication and signal transduction pathways. Other areas of research include the potential use of genomics, cell biology, transgenic mice, and structural biology for drug discovery, drug metabolism, and the elucidation of neurodegenerative mechanisms.

Graduate Training

Molecular pharmacology is one of the concentrations offered as part of the School of Medicine’s Interdisciplinary Biomedical Graduate Program. Biomedical research in this discipline focuses on the mechanisms of intracellular signaling using a combination of approaches (biochemical, molecular biological, biophysical, and others) as the basis for developing and testing new therapeutic agents. Applications are directed primarily at cancer pharmacology, neuropharmacology, and cardiovascular and endocrine pharmacology. A broad, multidisciplinary approach to training in modern molecular pharmacology is offered through formal interactions with the University of Pittsburgh Cancer Institute, the Center for Neuroscience, and the Center for Clinical Pharmacology, among other programs. Selected Research Highlights Bruce A. Freeman, Ph.D., studies the

production, reaction, and signal transduction properties of oxidizing and free radical inflammatory mediators in eukaryotic cells. Free radicals are highly reactive molecular structures that contribute to necessary biological processes like cell signaling but can also participate in side reactions that produce cell damage. As a result, they have been implicated

in atherosclerosis, symptoms of aging, and many cancers. Freeman’s laboratory examines the action of free radical species as signaling mediators under basal conditions and as pathogenic agents in inflammatory diseases. His group has elucidated the actions of numerous free radicals and their derivatives, lending new insight into cell signaling, and has revealed new therapeutic strategies for acute inflammation, metabolic syndrome, respiratory disorders, and cardiovascular diseases. Mitogen-activated protein kinase phosphatase 1 (MKP-1) is a tyrosine phosphatase superfamily member that dephosphorylates and inactivates mitogen-activated protein kinase (MAPK) substrates. Many essential cellular processes associated with human diseases are regulated by MAPK substrates, but few pharmacological inhibitors have been described. John S. Lazo, Ph.D., and colleagues have screened a tricyclic pyrrole-2-carboxamide library and found that 10 of 172 members inhibited human MKP-1—a remarkably high rate for a chemical library. Two of the pyrrole carboxamides, PSI2106 and MDF2085, were especially potent in vitro inhibitors of recombinant human MKP-1 enzyme activity and showed selectivity for MKP-1 over other closely related

phosphatases. Computational examinations of surface properties near the catalytic site revealed that these phosphatases differ significantly in their electrostatic potential at the substrate binding site, and molecular docking studies revealed possible interaction sites for PSI2106 on MKP-1. These results suggest that pyrrole carboxamides may provide a foundation for the development of pharmacological probes and novel anticancer agents. DNA topoisomerase II (topo II)targeted drugs have been used for treatment of various malignancies. However, the use of these drugs is often complicated by the development of drug resistance and secondary leukemia. Jack C. Yalowich, Ph.D., and colleagues study the mechanisms underlying these complications. Etoposide, a drug that inhibits topo II, has been shown to increase the risk of developing secondary acute myelogenous leukemia. Yalowich and colleagues have determined that free radical activation in HL60 (human myeloid leukemia) cells is generated by the presence of myeloperoxidase. The researchers believe that the free radical activation leads to oxidative DNA damage and subsequent leukemia. They have established that free radical formation could be suppressed by pretreatment with a heme synthesis inhibitor like succinylacetone, which reduces levels and activity of myeloperoxidase. Yalowich’s laboratory is also investigating the use of nutritional antioxidants like vitamin C and vitamin E derivatives to limit the adverse consequences of chemotherapy. Several department researchers are investigating the link between lung tumor cells and estrogen and the implications for development of estrogen-disruptive therapies. Jill M. Siegfried, Ph.D., has shown that lung cancer cells grow in response

to estrogen and that the number of estrogen receptors in lung cancer cells is comparable to that found in breast cancer cells. Laura A. Stabile, Ph.D., has determined that combined treatment with gefitinib, a drug that blocks the epidermal growth factor receptor, and fulvestrant, an antiestrogen agent, reduces lung tumor volume by 59 percent; in addition, many remaining tumor cells were found to be dead or dying. Individual treatment with these drugs resulted in a decrease of 49 percent (gefitinib) or 32 percent (fulvestrant) in tumor volume, with fewer dead and dying cells in the remaining tumor. The combined therapy is in a clinical trial pilot for women with advanced lung cancer. Using gene arrays, Pamela A. Hershberger, Ph.D., has found that some of the same growth genes induced by estrogen in breast cancer are also regulated by estrogen in lung cancer, the action of which is blocked by fulvestrant. John P. Wittschieben, Ph.D., has

determined that an enzyme called DNA polymerase zeta, or pol zeta, can help repair cells with extensive DNA damage. DNA polymerases are critical for copying, editing, and repairing genes and can make complete copies of DNA strands. If DNA is damaged for any reason, the action of most DNA polymerases is halted; however, pol zeta is not stopped by DNA lesions and retains the ability to help cells divide and avoid cell death. In collaboration with Richard D. Wood, Ph.D., Wittschieben has investigated the role of pol zeta in mouse cells. First, they knocked out the gene for Rev3L, which carries the lesionreplicating capabilities of pol zeta. This knockout proved fatal, so the researchers developed a Rev3L knockout with a genetic background where p53, a cell suicide-signaling molecule, is also knocked out. The cells in this model began to divide rapidly, and the investigators found that these cells display an increase in

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the swapping and fusing of genetic material between chromosomes as well as an increase in the number of chromosomes. A high degree of chromosomal instability is characteristic of cancer cells, and the human Rev3L gene is located in a segment of chromosome 6 where many tumorsuppressor genes are believed to be located. Wittschieben and Wood are now investigating whether chromosome 6 mutations can lead to cancer development by selectively deleting the Rev3L gene in adult mouse cells. Shivendra V. Singh, Ph.D., and

colleagues have identified the biological mechanisms underlying previous epidemiological findings that eating vegetables can reduce an individual’s risk for certain cancers. Cruciferous vegetables like broccoli, watercress, cabbage, and cauliflower contain chemicals called isothiocyanates, which are released when the vegetables are cut or chewed. Singh’s team found that phenethylisothiocyanate (PEITC) is effective in suppressing the growth of prostate cancer cells that have been transplanted into mice and that the dose of PEITC needed to suppress tumor growth can be achieved through dietary intake of cruciferous vegetables. Singh plans to move his work toward clinical trials to determine the effects of PEITC for prostate cancer prevention. Qiming J. Wang, Ph.D., studies the

mechanisms of tumor promotion, specifically the role of protein kinase C (PKC) in carcinogenesis. PKC, a target protein of the cell’s diacylglycerol signaling pathway, plays a critical role in the control of cell proliferation and malignant transformation. Phorbol esters, which are analogues of diacylglycerol, are efficient tools for detailed investigation of the diacylglycerol signaling pathway. Wang has demonstrated that phorbol esters control localization

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of intracellular PKC, thus allowing the esters to control PKC signaling. Her laboratory is also investigating differential regulation of PKC isoforms in normal and tumor cells; structural and regulatory factors that control PKCmediated responses; and the molecular basis underlying the divergent tumorpromoting activities of phorbol esters. Wang’s research is aimed toward the eventual design of novel PKC activators and inhibitors for the therapeutic intervention of PKC signaling in cancer and other diseases.

Regular Faculty Endowed Chairs Bruce A. Freeman, Ph.D. UPMC Irwin Fridovich Professor and Chair

John S. Lazo, Ph.D. Allegheny Foundation Professor Richard D. Wood, Ph.D. Richard M. Cyert Professor of Molecular Oncology Professors Donald B. DeFranco, Ph.D. William C. deGroat, Ph.D. Peter A. Friedman, Ph.D. William F. Furey Jr., Ph.D. Edwin K. Jackson, Ph.D. Joan M. Lakoski, Ph.D. Edwin S. Levitan, Ph.D. Jill M. Siegfried, Ph.D. Shivendra V. Singh, Ph.D. Associate Professors Daniel L. Altschuler, Ph.D. Julie L. Eiseman, Ph.D. Ferruccio Galbiati, Ph.D. Guillermo G. Romero, Ph.D. Jack C. Yalowich, Ph.D. Visiting Associate Professor Thomas P. Conrads, Ph.D. Research Associate Professor Paul A. Johnston, Ph.D.

Assistant Professors Alessandro Bisello, Ph.D. Jing Hu, M.D., Ph.D. Yu Jiang, Ph.D. Mark D. Nichols, Ph.D. Michael J. Palladino, Ph.D. Robert W. Sobol Jr., Ph.D. Qiming J. Wang, Ph.D. Lin Zhang, Ph.D. Research Assistant Professors Paul R.S. Baker, Ph.D. Pamela A. Hershberger, Ph.D. Elena Makhina, Ph.D. Fernando A.P. Ribeiro Neto, M.D. James R. Roppolo, Ph.D. Francisco Jose Schopfer, Ph.D. Adrian Sculptoreanu, Ph.D. Laura A. Stabile, Ph.D. Andreas Vogt, Ph.D. Instructors Palaniappa Arjunan, Ph.D. Daniela Galbiati, Ph.D. William B. Sneddon, Ph.D. John P. Wittschieben, Ph.D. Research Instructors Melanie Sarah Flint, Ph.D. Yung Kyu Kim, Ph.D. Edwina C. Kinchington, Ph.D. Lynn M. Knowles, Ph.D. Alicia M. Palladino, Ph.D. Dinara Mukhamat Shakiryanova, Ph.D. Elizabeth R. Sharlow, Ph.D. Harish Srinivas, Ph.D. Birgitte Oestergaard Wittschieben, Ph.D. Dong Xiao, M.D.

DEPARTMENT PROFILE

The Department of Physical Medicine and Rehabilitation provides comprehensive physiatric care for patients with limited mobility due to musculoskeletal injuries, spinal cord or traumatic brain injury, multiple sclerosis, cerebral palsy, amputations, and stroke. Services, which are offered in several UPMC hospitals and outpatient facilities, include up-to-date diagnostic options, surgical and nonsurgical treatments, and help with rehabilitative equipment. The department is committed to providing excellence in rehabilitative care through innovative research, interactive teaching, and professional personal service. Department physicians are experts in the fields of traumatic brain injury, spinal cord injury, stroke, diseases and disorders of the musculoskeletal and peripheral nervous systems, and other conditions that affect function and mobility. Research consists of lab and clinical investigations in areas like neuroprosthetics, neuroimaging, gene therapy, and assistive technology.

Residency and Fellowship Training

Selected Research Highlights

The department’s four-year residency program begins with an internship year of transitional medicine divided among inpatient rehabilitation, intensive care, internal medicine, neurology, rheumatology, radiology, and an elective; the remaining years are devoted to rehabilitation rotations. The program has a proven record of educating residents to a high level of clinical and academic proficiency. It includes an accredited fellowship in spinal cord injury and a fellowship in traumatic brain injury. Research is a requirement of the program and begins in the second year when residents are paired with an attending physician as a research mentor. Residents are taught the principles of research and encouraged to submit posters and abstracts to conferences and publications; a travel fund helps underwrite expenses. Training includes an annual research conference highlighting rehabilitation research completed by department residents as well as pre- and postdoctoral researchers throughout the University. The conference also features presentations by national and international leaders in rehabilitation research and medicine, student presentations, and awards.

Promising clinical evidence continues to demonstrate the effectiveness of motion-based therapies in treating low back pain. Gwendolyn A. Sowa, M.D., Ph.D., and colleagues are examining the biochemical pathways induced by mechanical force using in vitro rat intervertebral disc fibrochondrocytes cultured in either a healthy or an inflammatory environment. Cells were then exposed to tensile strain; and, after four hours, the mRNA expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), matrix metalloprotease-3 (MMP-3), matrix metalloprotease-13 (MMP-13), collagen I, collagen II, and aggrecan was measured. Cells in the inflammatory environment demonstrated an increase in proinflammatory mediator gene expression. Exposure to tensile strain significantly decreased the expression of iNOS, TNF-alpha, MMP-3, and MMP-13 in cells from the inflammatory environment, but no change was observed in healthy cells. These results demonstrate that physiologic levels of tensile strain act as a potent antiinflammatory signal and provide biochemical evidence for the beneficial effects of motion on the spine.

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Proprioception refers to an individual’s sensation of limb posture and movement. In addition to providing bodysense, proprioceptive feedback is important for motor learning and coordination and enables movements to be performed without visual guidance. Research in the laboratory of Douglas J. Weber, Ph.D., focuses on the neural signals that mediate proprioception. The aim is to understand the manner in which primary sensory neurons, especially muscle spindles, encode information about limb position and velocity. Weber’s results will be used to develop advanced neuroprosthetic devices that interface directly with the nervous system to provide sensory feedback and control. For example, by electrically stimulating primary sensory neurons, it is possible to generate conscious sensations of touch and movement. Weber and his team hope to develop a system to provide an amputee with tactile and proprioceptive sensations to make an artificial limb an integral sensorimotor apparatus rather than a lifeless machine attached to the body. Behavioral recovery following traumatic brain injury is hastened by acute treatment with the serotonin receptor agonist 8-OH-DPAT (8hydroxy-2-[di-n-propylamino]tetralin) or by chronic environmental enrichment. Anthony E. Kline, Ph.D., and colleagues are investigating whether combining these interventions would provide additional benefit. Adult male rats with traumatic brain injury received either 8-OH-DPAT or saline and were randomly assigned to either enriched or standard housing. Hippocampal neurons were quantified at three weeks post-injury, and both 8-OH-DPAT and environmental enrichment attenuated hippocampal area CA3 cell loss. Behavioral assessments using the Morris water maze

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showed that the group receiving 8-OH-DPAT plus the enriched environment significantly outperformed the group receiving 8-OH-DPAT alone, indicating a combination effect. However, there was no difference in performance when comparing 8-OH-DPAT versus saline in the enriched environment groups. Thus, while the study confirmed that both treatments improve recovery following traumatic brain injury, the treatment combination in this particular paradigm did not confer additional benefit. One explanation might be that the enriched environment is a highly effective treatment on its own, and the addition of 8-OH-DPAT confers no significant improvement.

Regular Faculty Professor Michael L. Boninger, M.D. Associate Professors Michael C. Munin, M.D. Joseph H. Ricker, Ph.D. Assistant Professors Fabrisia Ambrosio, Ph.D. Patricia Marie Arenth, Ph.D. Gilbert Brenes, M.D. Leonard R. Cabacungan, M.D. Alan W. Chu, M.D. Megan Helen Cortazzo, M.D. Kerry Gill Deluca, M.D. Brad E. DiCianno, M.D. Katherine M. Flood, M.D. Wendy M. Helkowski, M.D. John A. Horton III, M.D. Anthony E. Kline, Ph.D. Betty Y. Liu, M.D. Lisa Alison Lombard, M.D. Dana L. Martini, D.O. Billie Candice Pack, D.O. Louis E. Penrod, M.D. Mary Louise Russell, M.D. Jaspaal Singh, M.D. Gwendolyn A. Sowa, M.D., Ph.D. Amy K. Wagner, M.D. Wei Wang, M.D., Ph.D. Douglas J. Weber, Ph.D. Visiting Instructor Cara Elizabeth Reddy, M.D.

DEPARTMENT PROFILE

The Department of Psychiatry is dedicated to providing high-quality behavioral health care while developing and maintaining innovative basic and clinical research programs aimed at advancing clinical practice. Clinical care, which is based at Western Psychiatric Institute and Clinic, is centered on strong medical partnerships with other specialty areas, including primary care, internal medicine, and neurology, allowing for an enhancement of therapeutics and of outcomes research. The department’s research program embraces a collaborative format, forming translational bridges focused on the etiology of mental disorders, clinical treatment trials, methodological concerns, and outcome evaluation. This multidisciplinary approach to clinical medicine and research has led to pharmacological and psychotherapeutic interventions for specific diseases. It has also provided the foundation for world-class education and training programs.

Residency and Fellowship Training

Selected Research Highlights

The psychiatry residency program offers training in general psychiatry as well as subspecialty training in child and adolescent, geriatric, and forensic psychiatry. Residents may participate in either a clinical or research track. Both programs offer rigorous, comprehensive instruction and diverse clinical experience. Significant training is provided in psychopharmacology, psychotherapy and psychosocial interventions, neuroscience, public and community psychiatry, and psychiatric research. In addition, residents can work with experts in behavioral psychology, behavioral medicine, mental retardation/autism, psychiatric epidemiology, social and community psychiatry, forensic psychiatry, interviewing techniques, family and group therapies, and neuropsychology. The department also offers a triple board training program in partnership with Children’s Hospital of Pittsburgh of UPMC that combines general psychiatry, child and adolescent psychiatry, and pediatrics.

Beatriz Luna, Ph.D., studies the role an adolescent’s developing frontal cortex plays in executing cognitive tasks. Luna and her colleagues examined the development of response planning, a complex cognitive function, in a group of 8- to 30-year-olds to establish the stage at which adult performance levels are achieved. The researchers used the Tower of London (TOL) task, a neuropsychological test that requires planning and execution of a specific event sequence for goal attainment, to measure response planning ability. Participants were placed into three groups based on age: child (8–13), adolescent (14–17), and adult (18–30). Results revealed that TOL performance did not differ between the adolescent and adult groups, indicating that cognitive maturity for response planning occurs when one reaches adolescence. Luna has proposed that frontal cortex activity is correlated to impulsive behavior in teenagers. Because TOL success requires maturation of the prefrontal cortex, an individual’s performance on this task may reveal developmental lags and could be used to interpret cognitive maturity in adolescents.

Studies have suggested that low activity levels correlate with excess weight in adults, but none have determined whether low activity is a cause or a consequence of being overweight. Judy L. Cameron, Ph.D., and colleagues at Oregon Health and Science University studied activity levels in female rhesus monkeys over a period of nine months. The researchers determined that although all of the monkeys gained weight during the study period, those with the highest activity levels gained significantly less weight. In addition, activity levels for individual monkeys remained stable over the nine-month period, indicating that increased weight did not decrease activity. Cameron and colleagues found that food intake did not correlate with weight gain and, in a previous study, had shown that time of day, specifically nighttime eating, is not correlated with weight gain. Together, these findings lend credence to the idea that physical activity is important in weight regulation. Katherine L. Wisner, M.D., M.S., and

colleagues have studied the effectiveness of two common antidepressant classes on postpartum depression. They evaluated a selective serotonin reuptake inhibitor (sertraline) and a tricyclic antidepressant (nortriptyline) because both drugs are effective in treating general depression in women and have been shown to be safe for use while breastfeeding. The researchers evaluated the women for remission of depressive symptoms at four, eight, and 24 weeks following treatment onset. They found that the two medications were similarly effective. By four weeks, 46 to 56 percent of participants had responded to the drug, and 27 to 30 percent had symptom remission. By 24 weeks, nearly 100 percent of participants had responded, and almost 80 percent remitted. In many cases, response to antidepressants can take six to eight weeks, which Wisner considers too

long for treating postpartum depression. A demonstration that more than half of women either responded or remitted by four weeks provides encouragement that these drugs are appropriate for this purpose. Bipolar disorder, or manic depressive disorder, most often emerges in adolescence but has been studied primarily in adults. To fill the gap, Boris Birmaher, M.D., and colleagues have mapped the progression of bipolar disorder in children and adolescents. The researchers interviewed participants, ages 7 to 17, every 35 weeks for a period of two years to evaluate their symptoms using well-accepted clinical evaluation tools. They found that children and adolescents, as compared to adults, cycle more quickly between symptomatic periods of depression and mania. In addition, Birmaher and colleagues noted that 20 to 25 percent of participants experienced a significant transition to more severe symptoms over the course of the study, often necessitating a recategorization within the bipolar disorder spectrum and demonstrating a more rapid change than one would expect in adults over the same time period. In another study on bipolar disorder, Ellen Frank, Ph.D., has shown that certain forms of psychotherapy can help prevent illness recurrence when used in combination with traditional drug therapies. Interpersonal and social rhythm therapy (IPSRT) teaches patients to identify how changes in their daily routines and social relationships affect their moods. Patients work to identify situations that trigger mania or depression and, through IPSRT, create ways to manage these situations more effectively. Frank found that patients in good physical health who received IPSRT during an acute phase of illness were more likely to remain well during a twoyear follow-up period. Patients with multiple medical problems and/or anxiety fared better with intensive

clinical management therapy because it targets their physical symptoms. Both studies, however, support the use of psychotherapy to augment drug therapies in bipolar disorder. Chronic stress has been shown to decrease the volume of the hippocampus, a brain region that supports learning and memory and regulates neuroendocrine activity, in animals and in humans with stress-related psychiatric syndromes. Karen A. Matthews, Ph.D., and colleagues have examined the effects of chronic stress on healthy postmenopausal women without a clinical syndrome. The researchers measured life stress using the Perceived Stress Scale (PSS) across a 20-year period and later examined hippocampal grey matter volume. They found that higher PSS scores across the 20 years, indicating greater chronic life stress, predicted decreased grey matter volume in the right orbitofrontal cortex and right hippocampus. The stress-volume relationship persisted even after the researchers accounted for potentially confounding risk factors like age, total grey matter volume, time since menopause, use of hormone therapy, and subclinical depressive symptoms. The results suggest that chronic stress-related variations in brain morphology are related to adaptive and maladaptive changes in cognition, neuroendocrine activity, and psychiatric vulnerability. Mild cognitive impairment (MCI), a transitional stage between normal cognition and Alzheimer’s disease, exists in two forms. MCI amnesic (MCI-A) subtype produces memory loss only, whereas MCI multiple cognitive domain (MCI-MCD) subtype impairs judgment or language but typically does not involve memory loss. James T. Becker, Ph.D., and Oscar L. Lopez, M.D. (Department of Neurology), collaborated with researchers at the University of California, Los Angeles, to determine

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whether the two conditions are separate or whether one precedes the other in the progression to Alzheimer’s disease. The team used a new 3-D magnetic resonance imaging mapping procedure to examine specific brain areas. Results showed that the hippocampus, a key area of the brain in memory formation, is 14 percent smaller in patients with MCI-A than in normal individuals. (In Alzheimer’s disease, the shrinkage is 23 percent.) However, patients with MCI-MCD showed only a 5 percent loss of hippocampal tissue. These results confirmed two distinct pathways to Alzheimer’s disease and indicated that discerning pathway details could aid in developing treatments that slow or stop the progression of Alzheimer’s disease. In addition, the study showed that the highly detailed imaging technique can be used to track disease progress and treatment efficacy.

Centers Advanced Center for Interventions and Services Research for Early Onset Mood and Anxiety Disorders David A. Brent, M.D. Director Affect Regulation and Adolescent Brain Center Ronald E. Dahl, M.D. Director Conte Center for the Neuroscience of Mental Disorders David A. Lewis, M.D. Director Advanced Center for Intervention and Services Research for Late-Life Mood Disorders Charles F. Reynolds III, M.D. Director Pittsburgh Mind / Body Center (Understanding Shared Psychobiological Pathways) Karen A. Matthews, Ph.D. Director

Regular Faculty Endowed Chairs David A. Brent, M.D. Professor of Psychiatry (Suicide Studies)

Ronald E. Dahl, M.D. Staunton Professor of Pediatrics and Psychiatry David J. Kupfer, M.D. Dr. Thomas Detre Professor and Chair David A. Lewis, M.D. UPMC Professor of Translational Neuroscience Charles F. Reynolds III, M.D. UPMC Professor of Geriatric Psychiatry Neal D. Ryan, M.D. Dr. Joaquim Puig-Antich Professor of Child and Adolescent Psychiatry WPIC Chair in Public Psychiatry (open) Chair in Early Onset Bipolar Disease (open) Distinguished Service Professors Thomas Detre, M.D. Rolf Loeber, Ph.D. Professors Carol M. Anderson, Ph.D., M.S.W. Andrew S. Baum, Ph.D. James T. Becker, Ph.D. Boris Birmaher, M.D. Daniel J. Buysse, M.D. Judy L. Cameron, Ph.D. Jonathan D. Cohen, M.D., Ph.D. Jack R. Cornelius, M.D., M.P.H. Dennis C. Daley, Ph.D. Nancy L. Day, Ph.D. Mary Amanda Dew, Ph.D. Horacio Fabrega Jr., M.D. John D. Fernstrom, Ph.D. Ellen Frank, Ph.D. Mary Ganguli, M.D., M.P.H. Rohan Ganguli, M.D. Roger F. Haskett, M.D. Shirley Y. Hill, Ph.D. Rolf G. Jacob, M.D. J. Richard Jennings, Ph.D. Walter H. Kaye, M.D. Matcheri S. Keshavan, M.D. William E. Klunk, M.D., Ph.D.

David J. Kolko, Ph.D. Maria Kovacs, Ph.D. Marsha D. Marcus, Ph.D. Karen A. Matthews, Ph.D. Nancy J. Minshew, M.D. Timothy H. Monk, Ph.D., D.Sc. Benoit H. Mulsant, M.D. Edward P. Mulvey, Ph.D. Robert D. Nebes, Ph.D. Herbert L. Needleman, M.D. Vishwajit L. Nimgaonkar, M.D., Ph.D. Eric A. Nofzinger, M.D. Kenneth A. Perkins, Ph.D. Jay W. Pettegrew, M.D. Mary Phillips, M.B.B.Ch. Paul A. Pilkonis, Ph.D. Bruce G. Pollock, M.D., Ph.D. Jules Rosen, M.D. Loren H. Roth, M.D., M.P.H. Christopher M. Ryan, Ph.D. Richard Schulz, Ph.D. Paul H. Soloff, M.D. Michael E. Thase, M.D. Katherine L. Wisner, M.D., M.S. George S. Zubenko, M.D., Ph.D. Visiting Professors John W. Kasckow, M.D., Ph.D. Wun Jun Kim, M.D. Research Professor Jeffrey K. Yao, Ph.D. Associate Professors Sue R. Beers, Ph.D. Charles W. Bradberry, Ph.D. Charlotte Brown, Ph.D. Oscar G. Bukstein, M.D., M.P.H. Meryl A. Butters, Ph.D. Kadiamada N.R. Chengappa, M.D. Tammy A. Chung, Ph.D. Duncan B. Clark, M.D., Ph.D. Patricia A. Cluss, Ph.D. Marie D. Cornelius, Ph.D. Bernard J. Devlin, Ph.D. Andrea F. DiMartini, M.D. John E. Donovan, Ph.D. Andrea Fagiolini, M.D. Madelyn H. Fernstrom, Ph.D. Edward S. Friedman, M.D. Gretchen L. Haas, Ph.D. Martica Hall, Ph.D. Benjamin L. Handen, Ph.D. Robert H. Howland, M.D. Eric J. Lenze, M.D. Martin J. Lubetsky, M.D. Beatriz Luna, Ph.D. Robert S. Marin, M.D.

Christopher S. Martin, Ph.D. Lynn M. Martire, Ph.D. Mark D. Miller, M.D. Brooke S.G. Molina, Ph.D. Lisa A. Morrow, Ph.D. Richard K. Morycz, Ph.D. Jeffrey L. Peters, M.D. Ravinder D. Reddy, M.D. Gale A. Richardson, Ph.D. Greg J. Siegle, Ph.D. Bradley D. Stein, M.D., Ph.D. Magda Stouthamer-Loeber, Ph.D. Robert A. Sweet, M.D. Kenneth S. Thompson, M.D. Visiting Associate Professor Michael J. Travis, M.B.B.S. Research Associate Professor Stuart R. Steinhauer, Ph.D. Assistant Professors Kurt Ackerman, M.D., Ph.D. Howard J. Aizenstein, M.D., Ph.D. David A. Axelson, M.D. Maher O. Ayyash, M.B.Ch.B. Srihari Bangalore, M.B.B.S., M.P.H. Ranita Basu, M.D. Monica Beneyto, Ph.D. Gennady Berezkin, M.D. Ashok J. Bharucha, M.D. Kimberly A. Blair, Ph.D. Jaspreet S. Brar, M.B.B.S., Ph.D., M.P.H. Jeffrey D. Burke, Ph.D. Umapathy Channamalappa, M.B.B.S. Raymond Young-Jin Cho, M.D. Susanna S. Choi, M.D. Kodavali V. Chowdari, Ph.D. Ruth Condray, Ph.D. Cynthia A. Conklin, Ph.D. Tiberiu F. Bodea Crisan, M.D. Mario Cruz, M.D. Jill M. Cyranowski, Ph.D. Robert S. Dealy, M.D. Timothey C. Denko, M.D. Frank R. DePietro, M.D., Ph.D. Antoine B. Douaihy, M.D. George G. Dougherty, M.D. Linda J. Ewing, Ph.D., R.N. Russell M. Farr, M.D. Kenneth N. Fish, Ph.D. Erika E. Forbes, Ph.D. Steven D. Forman, M.D., Ph.D. William Gordon Frankle, M.D. Gaurav Gandotra, M.B.B.S. Ronald G. Garbutt, M.D. Anne Germain, Ph.D.

Frank A. Ghinassi, Ph.D. Peter J. Gianaros, Ph.D. Andrew R. Gilbert, M.D. Ariel G. Gildengers, M.D. Ronald M. Glick, M.D. Benjamin I. Goldstein, M.D. Tina R. Goldstein, Ph.D. Guillermo R. Gonzalez-Burgos, Ph.D. Tad T. Gorske, Ph.D. Nicola S. Gray, M.D. Carol M. Greco, Ph.D. Ghennady Gushchin, M.D., Ph.D. Ahmad R. Hariri, Ph.D. Alison E. Hipwell, Ph.D. Diane Holder, M.S.W. Marcela Horvitz-Lennon, M.D., M.P.H. Robert Hudak, M.D. Emil H. Ivanov, M.D. N.J. Jacob, M.B.B.S. Michael J. Jacobson, M.D. Hank P. Jedema, Ph.D. Charles E. Kahn, M.D. Melissa A. Kalarchian, Ph.D. Jordan F. Karp, M.D. Thomas M. Kelly, Ph.D. Jane N. Kogan, Ph.D. Cecile D. Ladouceur, Ph.D. Cynthia Larkby, Ph.D. Michele D. Levine, Ph.D. Xianchen Liu, M.D., Ph.D. Francis E. Lotrich, M.D., Ph.D. Fadi Maalouf, M.D. Erin E. Malley, M.D. Oommen K. Mammen, M.D. Pravat K. Mandal, Ph.D. Michael P. Marshal, Ph.D. Christine A. Martone, M.D. Cameron L. McGavin, M.D. John J. McGonigle, Ph.D. Nadine Melhem, Ph.D. Viveca A. Meyer, M.D. Jennifer Q. Morse, Ph.D. Eydie L. Moses-Kolko, M.D. Douglas E. Moul, M.D., M.P.H. Peter D. Murray, M.D. Jeremy S. Musher, M.D. Kenneth C. Nash, M.D. Roberto Ortiz-Aguayo, M.D. Dustin Pardini, Ph.D. Kevin R. Patterson, M.D. Charles Perrotta Jr., M.D. Joseph Nicholas Pierri, M.D. Harold B. Pinkofsky, M.D., Ph.D. Konasale M. Prasad, M.D., M.B.B.S. Sarah K. Reynolds, Ph.D. Stephanie S. Richards, M.D. Eric D. Rickin, M.D.

Jason B. Rosenstock, M.D. Paola Rucci, Dr.Stat. Mukesh Sah, M.B.B.S. Karen L. Schmidt, Ph.D. Etienne Sibille, Ph.D. Jennifer S. Silk, Ph.D. Amarpreet Singh, M.D. Dorothy K.Y. Sit, M.D. Lalith K. Solai, M.B.B.S. Duane G. Spiker, M.D. Sabato Anthony Stile, M.D. Martin Thomas Strassnig, M.D. Holly A. Swartz, M.D. Katalin Szanto, M.D., Ph.D. Eva M. Szigethy, M.D., Ph.D. James Dismore Tew Jr., M.D. Dawn Lindsay Thatcher, Ph.D. Rebecca Clark Thurston, Ph.D. Nicholas Tsopelas, M.D. Rameshwari V. Tumuluru, M.B.B.S. Petronilla Vaulx-Smith, M.D., Ph.D. Gautami Veeragandham, M.B.B.S. Elizabeth M. Venditti, Ph.D. Ellen M. Whyte, M.D. Jennifer A. Willford, Ph.D. Dorothy V. Wilson, M.D. Ann Zachariah, M.B.B.S. Stephen A. Zerby, M.D. Allan M. Zuckoff, Ph.D. Research Assistant Professors Carmen Andreescu, M.D. Alexandre Yurievitch Dombrovski, M.D. Barbara Hanusa, Ph.D. Takanori Hashimoto, M.D., Ph.D. Amy D. Herschell, Ph.D. Leonid Semion Krimer, M.D. Kanagasabai Panchalingam, Ph.D. Lan Yu, Ph.D. Instructor Lee K. Wolfson, M.Ed. Visiting Instructors Rebecca M. Ringham, Ph.D. Isabella Soreca, M.D. Research Instructor Dalila Akkal, Ph.D.

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Joel S. Greenberger, M.D., Claude Worthington Benedum Foundation Professor and Chair

Scott A. Mirowitz, M.D., Professor and Chair

DEPARTMENT PROFILE

Dwight E. Heron, M.D., and Sushil

The Department of Radiation Oncology, which focuses on clinical and research activities as well as medical physics, provides radiotherapy services to 10 UPMC hospitals and oversees the treatment of approximately 6,000 new patients a year. Radiation therapy clinical programs include conventional external beam, three-dimensional conformal irradiation, intensity-modulated radiation therapy, fractionated stereotactic irradiation (Trilogy, CyberKnife®), and stereotactic radiosurgery (Gamma Knife®). In addition, the department offers a full array of brachytherapy services, including interstitial and intracavitary high-dose-rate implants, permanent radioactive implants, intraoperative brachytherapy, and minimally invasive techniques. A comprehensive clinical care program at 20 radiation oncology facilities in western Pennsylvania provides a centralized and advanced radiation treatment program for all major forms of cancer. The department’s research programs in molecular biology, radiation biology, and stem cell biology are integrated with multidisciplinary protocols in medical and surgical oncology at the University of Pittsburgh Cancer Institute (UPCI).

Beriwal, M.D., are examining the

Residency and Fellowship Training

Selected Research Highlights

The department’s residency program engages resident physicians in intraand interdepartmental academic and clinical efforts. Rotations are organized into disease-oriented blocks, and residents train at three clinical sites on campus and at UPCI. Multidisciplinary training is provided in central nervous system and hematological malignancies, gastrointestinal oncology, lung and genitourinary cancers, breast and gynecological oncology, pediatric oncology, and head and neck malignancies. Residents are also trained in the use of modern radiation therapy and brachytherapy for treatment of various cancers.

Joel S. Greenberger, M.D., and Michael W. Epperly, Ph.D., are investigating the use of intravenous gene therapy to protect vital organs and tissues against large-scale exposure to ionizing radiation as would occur from a radiological or nuclear bomb. Such whole-body, large-dose irradiation would prove fatal within 30 days for a significant portion of the population. Greenberger and Epperly have shown in mice that intravenous administration of manganese superoxide dismutase plasmid liposome (MnSOD-PL) protects bone marrow from wholebody irradiation and significantly prolongs survival compared to controls. For a moderately high dose of radiation (9 Gy [gray]), 80 percent of controls survive to 30 days postexposure compared to 93.3 percent of mice injected with MnSOD-PL. However, when the radiation dose increases to 9.75 Gy, 30-day survival in control animals plummets to 12.5 percent compared to a smaller decrease (75 percent survival) in MnSOD-PL animals.

efficacy of extended-field intensitymodulated radiation therapy (IMRT) for cervical cancer. Traditional cervical cancer radiation therapies irradiate a wide area (pelvis and abdomen); because of this, only moderate doses can be delivered. Even so, 40 percent of patients experience serious side effects like pain, diarrhea, and bowel obstruction. By contrast, extended-field IMRT targets high-energy beams directly to the tumor site, passing through normal tissue without imparting damage. The convergent beams allow higher radiation doses with minimal adverse side effects. In a recent study, Heron and Beriwal treated 36 cervical cancer patients with extended-field IMRT in combination with cisplatin, a chemotherapeutic agent. Thirty-four patients responded completely to treatment and experienced minimal side effects, demonstrating reduced toxicity for this approach. While 11 of the patients developed recurrences, most appeared in distant sites, suggesting that additional systemic therapies could help to control metastasis in cervical cancer. Genes damaged by radiation exposure, environmental toxins, free radicals, and other harmful influences can lead to cancers or other diseases. Christopher J. Bakkenist, Ph.D., studies the most lethal form of DNA damage, the double-strand break (DSB). His particular focus is the ataxia telangiectasia mutated (ATM) enzyme, a nuclear protein kinase essential for cellular response to DSBs. Bakkenist and his research team have shown that inactive ATM

proteins are locked into dimers, a pairing that prevents unwanted interactions with other proteins. However, in the presence of DSBs, ATM proteins separate into active monomers that trigger molecular cascades, culminating in either DNA repair or cell death. Bakkenist has determined that activated ATM monomers phosphorylate target proteins, which then signal activity further down the repair pathway and are also responsible for additional ATM dimer separation. Bakkenist’s team has found that even a small quantity of DSBs can initiate ATM response within minutes of the damage; once initiated, the response rapidly amplifies. Understanding the mechanisms of DSB repair could eventually lead to novel preventive and treatment approaches for disorders related to dysfunctional DNA repair.

Regular Faculty Endowed Chairs Melvin D. Deutsch, M.D. Dr. Raul Mercado Professor

Joel S. Greenberger, M.D. Claude Worthington Benedum Foundation Professor and Chair Professor John C. Flickinger, M.D. Associate Professors Tao Cheng, M.D. Michael W. Epperly, Ph.D. Dwight E. Heron, M.D. Chyongchiou Jeng Lin, Ph.D. Assistant Professors Yoshio Arai, M.D. Christopher J. Bakkenist, Ph.D. Susan M. Rakfal, M.D. Research Instructors Yunyun Niu, M.D., Ph.D. Xichen Zhang, M.D.

DEPARTMENT PROFILE

The Department of Radiology is composed of eight subspecialty clinical divisions—Abdominal Imaging, Musculoskeletal Imaging, Neuroradiology, Nuclear Medicine, Pediatric Radiology, Thoracic Imaging, Vascular and Interventional Radiology, and Women’s Imaging. These divisions form the organ system approach upon which the department’s clinical structure is built, allowing radiologists with particular expertise to interact and collaborate with clinicians with similar interests. The department also has a community division, which comprises hospitals and imaging centers in and around the Pittsburgh region. The department’s research program includes four divisions — Magnetic Resonance (MR) Research, Positron Emission Tomography (PET) Research, Radiology Imaging, and Radiology Informatics.

Residency and Fellowship Training

All trainees are required to complete at least one year of postgraduate training before entering the department’s four-year radiology residency program. Residents rotate through all subspecialties of radiology at UPMC Presbyterian, UPMC Shadyside, UPMC Montefiore, Children’s Hospital of Pittsburgh of UPMC, the VA Pittsburgh Healthcare System, and Magee-Womens Hospital of UPMC. Residents also participate in a sixweek radiologic-pathologic correlation course at the Armed Forces Institute of Pathology in Washington, D.C. After residency, most trainees take part in one of two accredited fellowships (neuroradiology and pediatric radiology) or one of four nonaccredited fellowships (abdominal imaging, musculoskeletal imaging, PET, and women’s imaging). Clinical Divisions Abdominal Imaging Michael P. Federle, M.D. Chief

The Division of Abdominal Imaging provides imaging, diagnosis, and treatment for diseases of the adult abdomen and pelvis. Included in this division are sections on body-computed tomography, gastrointestinal radiology, genitourinary radiology, magnetic resonance imaging, and ultrasound. Physicians in this division also evaluate

certain nonabdominal conditions, including pharyngeal and esophageal disease in the gastrointestinal radiology section and thyroid, scrotal, vascular, and extremity abnormalities in the ultrasound section. Research in this division focuses on organ transplantation, hepatobiliary disease, trauma, and medical informatics. The division is also investigating ways to use intravenous contrast agents to enhance computed tomography and magnetic resonance imaging. Musculoskeletal Imaging Cynthia A. Britton, M.D. Interim Chief

The Division of Musculoskeletal Imaging provides clinical interpretation of X-ray films and diagnostic tests involving computed tomography (CT), bone densitometry, magnetic resonance imaging, and arthrography. The division also performs various interventional procedures, including biopsies and pain management procedures. Clinical evaluation is provided directly at certain locations; in other cases, remote imaging software and filmless radiology technology developed by the Division of Radiology Informatics are used. In its basic and clinical research, the Division of Musculoskeletal Imaging collaborates extensively with the Departments of Orthopaedic Surgery and Physical Medicine and Rehabilitation.

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DEPARTMENTS

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Neuroradiology William Rothfus, M.D. Chief

Pediatric Radiology Manuel P. Meza, M.D. Chief

The Division of Neuroradiology routinely uses CT angiography with three-dimensional reconstruction for noninvasive diagnosis of cerebrovascular disease and performs specialized diagnostics, including sialography, modified bariumswallowing studies, and combined PET/CT imaging of head and neck cancers. The division’s spine intervention service oversees discography, epidural steroid injections, selective nerve root blocks, biopsies, and vertebral augmentation (kyphoplasty and vertebroplasty). Endovascular neuroradiology, which is also part of this division, involves angiograms as well as interventional radiography for intracranial aneurysms, arteriovenous malformations, tumors, and arteriovenous fistulae.

The Division of Pediatric Radiology is one of the nation’s oldest and largest pediatric radiology programs. The division is committed to subspecialty imaging to complement its strengths in general radiology. Faculty members’ research interests include the radiographic manifestations in organ transplantation, pediatric neuroradiology, interventional techniques in the pediatric population, magnetic resonance imaging in pediatric patients, pediatric stroke, imaging of traumatic speech disorders, and bone mineral density in pediatric patients receiving corticosteroids for leukemia or cancer.

Nuclear Medicine James M. Mountz, M.D., Ph.D. Chief

The Division of Nuclear Medicine provides a full range of clinical services with a major focus on the treatment of thyroid diseases and thyroid cancer as well as radioimmunotherapy of lymphomas. Diagnostic procedures include PET, PET/CT, and SPECT (single positron emission computed tomography) as well as a menu of highly specialized procedures like F-18 fluorodeoxyglucose PET for Alzheimer’s disease evaluation. The division is also active in evaluating and staging neuroendocrine tumors in adult and pediatric patients. Clinical programs in the PET facilities include the evaluation of patients with epilepsy and a variety of oncologic diseases, including solitary pulmonary nodules, lung cancer, colon cancer, melanoma, brain tumors, head and neck cancer, and esophageal cancer.

Thoracic Imaging Carl R. Fuhrman, M.D. Chief

The Division of Thoracic Imaging focuses on the accurate and timely interpretation of chest imaging studies, including chest radiographs, thoracic CT and MR exams, cardiac MR and CT, and combined PET/CT imaging of primary chest abnormalities and thoracic diseases. The division interprets chest radiographs for tuberculosis screenings by the Allegheny County Health Department and for local participants in the National Cancer Institute’s Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Research being done by the division involves emphysema imaging, lung cancer screening, cardiac imaging, and characterization of growth patterns for pulmonary nodules.

Vascular and Interventional Radiology Albert B. Zajko, M.D. Chief

The Division of Vascular and Interventional Radiology performs nonneuroradiographic angiographic, venographic, and interventional radiological procedures. Angiographic procedures include diagnostic problems of the neck, thorax, abdomen, and peripheral blood vessels. Vascular interventions performed by the division include balloon angioplasty and stenting of peripheral and renal arterial lesions; embolotherapy for the treatment of tumors or gastrointestinal tract bleeding; embolization for the treatment of traumatic injuries, varicoceles, and pulmonary arteriovenous malformations; and thrombolytic therapy for arterial, venous, and graft occlusions. Nonvascular procedures include percutaneous biliary drainage, balloon dilation of biliary structures, nephrostomy and percutaneous removal of retained postoperative common duct stones, and select percutaneous biopsies. Division research includes clinical testing of a new hand-held ultrasound display device called the Sonic Flashlight. Women’s Imaging Jules H. Sumkin, D.O. Chief

The Division of Women’s Imaging is divided into two clinical sections: breast imaging and diagnostic imaging. The breast imaging section is committed to detecting breast cancer as early as possible in asymptomatic women and to handling symptomatic cases with the best possible techniques of digital mammography, sonography, image-guided breast biopsy, needle localization, ductography, and breast MR. The clinical objectives of the diagnostic imaging section are to provide diagnostic and intervention services for gynecologic oncology, infertility,

and pregnancy-related complications. Research in the division focuses on digital imaging technology, especially as it relates to breast imaging, computer-assisted diagnosis, and telemammography. Research Divisions Magnetic Resonance (MR) Research Fernando E. Boada, Ph.D. Director

The Division of MR Research functions through the Magnetic Resonance Research Center, which uses high magnetic field MR scanners in ongoing research involving broad foci, including neuroscience, medicine (cardiology, endocrinology), neurology (epilepsy, stroke), neurosurgery (Gamma Knife® therapy, presurgical planning for neurooncology), oncology, orthopaedics, psychiatry (dementia, mood disorders, mania, autism, schizophrenia), and psychology. Resources include 9.4-tesla, 7-tesla, and multiple 3-tesla and 1.5-tesla magnets. Positron Emission Tomography (PET) Research Chester A. Mathis, Ph.D. Director

The Division of PET Research focuses primarily on neuroscience studies, including cerebral blood flow and metabolism measurements, neuroreceptor systems, and assessment of the functional interactions of neurotransmitter systems. The division’s radiochemistry development program is working on new radiolabeled, injectable agents for a variety of applications. Major areas of emphasis include development of radioligands for amyloid imaging in Alzheimer’s disease as well as agents for the serotonin, dopamine, acetylcholine, and peripheral benzodiazepine receptor systems. Clinical studies focus on PET to evaluate skeletal muscle metabolism in diabetics and amyloid deposition in Alzheimer’s disease.

Radiology Imaging David Gur, Sc.D. Director

The Division of Radiology Imaging provides expertise in radiological physics, computer and information science, and evaluation of imaging systems. Most division activities involve digital imaging research. Other projects, which aim to improve the efficiency and efficacy of radiological imaging in the clinical environment, include assessing clinical devices and practices, exploring uses of electrical impedance screening, using X-ray in the diagnostic process, incorporating computer-aided diagnosis results with transmitted images from remote sites, developing computational measures of image fidelity, and optimizing image display to maximize the information content conveyed to the observer. Radiology Informatics Rasu Shrestha, M.D. Medical Director

The Division of Radiology Informatics is responsible for the design, implementation, support, and evaluation of picture archiving communication systems (PACS), teleradiology, and related informatics projects. Current research involves telemedicine, workstation design, distributed object development, wavelet-based image representation/compression, multimedia education authoring, viewing tool development, electronic medical record infrastructure development, and receiver operating characteristic (ROC) analysis. The Stentor® imaging system developed by a Silicon Valley company using software designed by division faculty enables timely interpretation of electronic images without film transport between facilities and allows for interactive consultation with physicians in clinical settings around the country. In addition, dynamic transfer syntax (DTS), which was developed by the division, provides image transmission and display technology generally using a clinical facility’s existing equipment.

Selected Research Highlights David Gur, Sc.D., and colleagues

have developed and tested a new multiview computer-aided detection (CAD) scheme for breast cancer. To evaluate the procedure’s sensitivity, it was applied to a patient database with images of known benign and malignant breast tissue. Gur and his team used a single-image CAD; and for each identified region, a matching strip of interest on the ipsilateral view was established. A multifeature artificial neural network scored the likelihood of the paired “matched” regions representing true-positive masses. The single-image CAD scheme achieved 74.4 percent sensitivity, where only half of the cases were detected with two single images and most false positives were detected with only one image. Applying the multiview CAD scheme, the sensitivity increased to 90.9 percent, and the false-positive detection rate was reduced by 23.7 percent. Quantifying changes in arterial and total cerebral blood volume (CBVa and CBVt, respectively) during neural activation might provide critical vascular control mechanism information and help to identify neurovascular response origins in conventional blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). Seong-Gi Kim, Ph.D., has quantified cerebral blood flow (CBF) as well as CBVa and CBVt using 9.4tesla MRI in isoflurane-anesthetized rats during 15-second forepaw stimulation. CBF and CBVa were simultaneously determined by tissue and vessel signal modulation using arterial spin labeling; CBVt was measured with a susceptibility-based contrast agent. Neural activity-induced absolute changes in CBVa and CBVt were statistically equivalent and independent of the size of the region analyzed, indicating that increased CBVt during neural activation in this region (somatosensory cortex) originates mainly from arterial blood volume changes and implying that venous blood volume changes may be negligible in BOLD MRI.

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Angela M. Gronenborn, Ph.D., UPMC Rosalind Franklin Professor and Chair

Tumor oxygenation plays a critical role in tumor growth, invasion, and therapy. Qiuhong He, Ph.D., and colleagues are developing a novel method to evaluate tumor oxygenation levels. Tumor cells exhibit various genetic and molecular characteristics and responses to therapeutic interventions, including radiation and chemotherapy, based on oxygenation levels. The invasive microelectrode approach is the current standard for tumor oxygenation measures, but it produces many artifacts. He and colleagues are using an attenuated strain of Salmonella typhimurium that selectively accumulates and proliferates in tumor tissues to develop a novel molecular imaging approach to map tumor oxygenation in vivo. Because salmonella can penetrate into the hypoxic tumor areas, the method will fully map tumor oxygenation; myoglobin that has been genetically engineered into the bacterium will serve as an oxygen sensor. This method offers the prospect of improved detection of primary tumors and distant metastases as well as better therapeutic planning and clinical outcomes monitoring.

Centers Magnetic Resonance Research Center Fernando E. Boada, Ph.D. Director

Professors A’Delbert Bowen III, M.D. Michael P. Federle, M.D. Charles R. Fitz, M.D. Carl R. Fuhrman, M.D. David Gur, Sc.D. Emanuel Kanal, M.D. Seong-Gi Kim, Ph.D. Scott A. Mirowitz, M.D. James M. Mountz, M.D., Ph.D. William Rothfus, M.D. Jules H. Sumkin, D.O. Albert B. Zajko, M.D. Visiting Professors Kyong Tae Bae, M.D., Ph.D. Lorcan A. O’Tuama, M.B.B.Ch. Research Professors Walter F. Good, Ph.D. Edwin M. Nemoto, Ph.D. Associate Professors Nikhil B. Amesur, M.D. Walter S. Bartynski, M.D. Fernando E. Boada, Ph.D. Barton F. Branstetter, M.D. Dev P. Chakraborty, Ph.D. James V. Ferris, M.D. Christiane M. Hakim, M.D. Joan M. Lacomis, M.D. Barry M. McCook, M.D. Manuel P. Meza, M.D. Philip D. Orons, D.O. Julie C. Price, Ph.D. Donald Sashin, Ph.D. F. Leland Thaete, M.D. Jeffrey D. Towers, M.D. Mitchell E. Tublin, M.D. Eric C. Wiener, Ph.D.

PET Research Center Chester A. Mathis, Ph.D. Director

Visiting Associate Professors Friedrich D. Knollmann, M.D. Charles Lee, M.D. Eric D. Schwartz, M.D. Margarita L. Zuley, M.D.

Regular Faculty

Research Associate Professor Bin Zheng, Ph.D.

Endowed Chairs Chester A. Mathis, Ph.D. Radiology PET Research Professor

Advanced Imaging Chair (open) Innovations in Imaging Chair (open) Molecular Imaging Chair (open)

Assistant Professors Gordon S. Abrams, M.D. Hesham Mohamed Ahmed, M.B.B.Ch. Omar Almusa, M.D. Kevin M. Baskin, M.D. Badreddine Bencherif, M.D. Andrew Gabriel Bleicher, M.D. Todd Michael Blodgett, M.D. David G. Buck, M.D. Jonathan Paul Carney, Ph.D. Victor J. Catullo, M.D. Cathy S. Cohen, M.D. Anil Kumar Dasyam, M.B.B.S. Christopher R. Deible, M.D., Ph.D. Edward Joel Escott, M.D. Mitsuhiro Fukuda, Ph.D. Marie A. Ganott, M.D. Saraswathi Golla, M.B.B.S. Kelly A. Haarer, M.D. Qiuhong He, Ph.D. Keyanoosh Hosseinzadeh, M.D. Marion Alicia Hughes, M.D. Tamer Selim Ibrahim, Ph.D. Kuo-Shyan Lin, Ph.D. Amy H. Lu, M.D. Fred M. Moeslein, M.D., Ph.D. Ashok Muthukrishnan, M.B.B.S. Rajesh Narendran, M.B.B.S., M.D. Ka-Kei Ngan, M.D. Kalliopi Agathangelos Petropoulou, M.D. Daniel Alexander Pryma, M.D. Ratan Shah, M.B.B.S. Dilip Digambar Shinde, M.B.B.S. Biatta Sholosh, M.D. Jawad Tsay, M.D. Research Assistant Professors Tao Jin, Ph.D. Charles M. Laymon, Ph.D. Joseph K. Leader III, Ph.D. Glenn S. Maitz, M.S. Neal Scott Mason, Ph.D. Claudia Regina Mello-Thoms, Ph.D. Chanhong Moon, Ph.D. Jiantao Pu, Ph.D. Paul A. Schornack, Ph.D. Costin Tanase, Ph.D. Xiao Hui Wang, M.D., Ph.D. Research Instructors Denise K. Davis, B.S. Guofeng Huang, Ph.D. Brian J. Lopresti, B.S. Iclal Ocak, M.D. Yongxian Qian, Ph.D.

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DEPARTMENT PROFILE

The Department of Structural Biology was established in 2005, bringing together investigators in the School of Medicine already studying the architecture and shape of biological macromolecules with newly recruited researchers and demonstrating the importance of this field in advancing biomedical investigations. The department occupies 32,000 square feet in the new Biomedical Science Tower 3 with a state-of-the-art laboratory custom-designed to meet the special needs of the sensitive equipment used by department researchers. Using techniques like X-ray crystallography, nuclear magnetic resonance spectroscopy, and cryo-electron microscopy, researchers work to determine atomic structures in order to provide information on protein interactions, biochemical mechanisms, active sites, motions important for function, and interfaces with other compounds. These studies aid in drug design and help elucidate mechanisms of human diseases.

Graduate Training

The Molecular Biophysics and Structural Biology Graduate Program is an interdisciplinary program at the interfaces of biology, chemistry, physics, and other traditional scientific disciplines. The program, which includes faculty from Pitt’s School of Medicine and School of Arts and Sciences as well as from Carnegie Mellon University, provides a unique opportunity for students to study across traditional boundaries and to train in state-of-the-art methodologies like high field solution and solid-state nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography, cryo-electron microscopy, atomic force microscopy, mass spectrometry, infrared spectroscopy, and computational molecular biology. Selected Research Highlights Angela M. Gronenborn, Ph.D., and

colleagues study the HIV-inactivating protein Cyanovirin-N (CV-N), a cyanobacterial lectin that exhibits potent antiviral activity at nanomolar concentrations by interacting with high-mannose carbohydrates on viral glycoproteins. The researchers have investigated CV-N mutants to establish the antiviral activity’s molecular mechanisms. Gronenborn and colleagues have found that mutations, which alter the trimannose specificity in one binding site or abolish the other sugar-binding site

(domain B), revealed that both carbohydrate binding sites are essential for antiviral activity. These findings clarify that the multivalent and multisite interactions are critical and that the nanomolar antiviral potency of CV-N is related to the mannoses’ constricted and spatially crowded arrangement on viral glycoproteins and is not due to CV-N-induced virus particle clustering, making CV-N a true viral entry inhibitor. Glycerol is a central link among the respiration, energy, sugar, and lipid metabolic processes. Joanne I. Yeh, Ph.D., and colleagues have conducted detailed structural studies on soluble and membrane protein partners mediating glycerol metabolism and have revealed novel signal transduction and regulatory interactions. Sn-Glycerol-3-phosphate dehydrogenase (GlpD) is an integral membrane protein whose enzymatic activity is regulated through its interaction with the inner membrane of E. coli. The importance of these pathways is indicated by the presence of homologous systems across organisms, including humans, where some of these processes take place on the mitochondrial membrane. In the absence of lipid-enzyme interactions, the GlpD enzyme remains in an inactive conformation. Yeh and colleagues have determined the structure of a fully active E. coli GlpD, revealing the unique topology of the enzyme, which exhibits a new fold in one domain as well as protein-protein

interaction surfaces whereby complex formation enhances activity. Glycerol metabolism has been implicated in mechanisms involved in insulin signaling, and metabolic perturbations in these pathways are linked to obesity in humans. These findings illuminate how membrane-enzyme interactions regulate activity, and the similarities found in GlpD homologs across organisms show that the prokaryotic structural results can likely be applied to eukaryotic GlpD enzymes to identify new means of combating conditions like diabetes and obesity. Hierarchical interactions in multiprotein complexes can be investigated using a combination of two methods, scanning calorimetry, which detects the temperatures at which certain interactions are disrupted, and cryoelectron microscopy, which reveals the accompanying structural changes. James F. Conway, Ph.D., and colleagues have used these methods to examine the procapsid of bacteriophage HK97 (Prohead I), which is composed of hexamers and pentamers of gp5, a precursor capsid protein. At neutral pH, Prohead I exhibits an endothermic transition at a temperature of 53ºC, and the researchers have shown that this transition is reversible. Conway and colleagues used cryo-electron microscopy to observe the structural expression of Prohead I at 60ºC and found a capsid species 10 percent larger than Prohead I. Visible changes were confined to the gp5 hexamers, which were thinned and flattened as they would be during the transition state of the normal maturation pathway. Conway and colleagues concluded that at ambient temperatures, gp5 hexamers are restrained from switching conformations but above 53ºC, the restraint is overcome. Gp5 pentamers, on the other hand, are more stably anchored and resist thermal perturbation. This finding provides important insight into the assembly pathway of the HK97 capsid and related viruses.

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Timothy R. Billiar, M.D., George V. Foster Professor and Chair

SURGERY

Judith H. Klein-Seetharaman, Ph.D.,

DEPARTMENT PROFILE

and colleagues study mutations in the protein rhodopsin that lead to retinitis pigmentosa (RP), a genetic disorder that produces night blindess, tunnel vision, and, eventually, blindness. The researchers have studied a number of mutations that lead to RP to determine whether a mutation’s location affects RP expression. Klein-Seetharaman and colleagues found that distinct amino acid substitutions cause different RP severity and progression rates. Specifically, both the R135L and R135W mutations (cytoplasmic end of H3) result in diffuse, severe disease (class A), but R135W causes more severe and more rapidly progressive RP than R135L. The P180A and G188R mutations (second intradiscal loop) exhibit a mild phenotype with regional variability (class B1) and diffuse disease of moderate severity (class B2), respectively. Their studies further established that rhodopsin misfolding is more pronounced in the R135W mutation, perhaps explaining at the molecular level why this mutation has a much more severe phenotype.

The Department of Surgery fosters a threefold mission: to provide high quality clinical care to surgical patients, to promote stateof-the-art educational programs in all areas of clinical surgery, and to produce new information from research that will advance surgical practice. The late Henry T. Bahnson, M.D., who chaired the department from 1963 to 1987, is credited with establishing it as a leading academic surgery department. In addition, the department has pioneered a tradition for innovation and excellence at the hands of such prominent surgeons as Thomas E. Starzl, M.D., Ph.D., the world-renowned transplant specialist for whom the department’s Thomas E. Starzl Transplantation Institute is named; Richard L. Simmons, M.D., a distinguished transplant surgeon, accomplished researcher, and respected mentor; and Bernard Fisher, M.D., who revolutionized surgical treatments for breast cancer through his elucidation of the systemic nature of the disease. Clinical activities in the department are diverse in specialty and setting; faculty members perform more than 80,000 surgical procedures a year. The department includes eight divisions: Cardiac Surgery, General Surgery, Pediatric Surgery, Plastic Surgery, Surgical Oncology, Thoracic and Foregut Surgery, Transplantation Surgery, and Vascular Surgery.

Regular Faculty Endowed Chair Angela M. Gronenborn, Ph.D. UPMC Rosalind Franklin Professor and Chair Visiting Professor Ronald B. Wetzel, Ph.D. Associate Professor Joanne I. Yeh, Ph.D. Visiting Associate Professor James F. Conway, Ph.D. Assistant Professors Rieko Ishima, Ph.D. Judith H. Klein-Seetharaman, Ph.D. Peijun Zhang, Ph.D. Research Assistant Professor Shoucheng Du, Ph.D.

Residency and Fellowship Training

Divisions

The department has four surgical residency programs leading to primary board certification in general surgery, cardiothoracic surgery, plastic surgery, or vascular surgery, plus subspecialty fellowships in surgical oncology, transplantation surgery, hepatobiliary surgery, pediatric surgery, critical care, and hand surgery. Participation by residents in independent, ongoing research projects is strongly encouraged. In addition, the residency program is designed to provide special experience and training for those interested in academic surgery. For residents and others, the department provides training through the Charles Gray Watson Surgical Education Center, which was developed with the insight that much surgical training must occur outside the operating room. The mission of the Watson Center is to improve patient care, facilitate development of innovative technologies for training (e.g., surgical simulators), promote mastery of surgical techniques, and provide access to a learning center 24 hours a day.

Cardiac Surgery Kenton J. Zehr, M.D. Chief

The focus of the Division of Cardiac Surgery is prevention of end-stage heart and lung failure through therapies and technologies that promote the recovery and repair of the heart and lungs or provide replacement alternatives. The division’s world-leading transplant program includes three interrelated components: heart transplants, mechanical circulatory support or artificial heart devices, and lung transplants. Research in the division parallels its clinical activities and focuses on clinical outcomes, immunopathology, rehabilitative and quality of life studies, clinical trials in immunosuppression and left ventricular assist devices, and basic research in organ preservation and regenerative medicine, including cellular and genetic therapies.

General Surgery Andrew B. Peitzman, M.D. Chief

The focus of the Division of General Surgery ranges from minimally invasive surgery to trauma surgery; it is the home of the state’s busiest trauma program. The minimally invasive surgery section specializes in bariatric surgery and carries out NIH-sponsored outcomes research. Trauma section research includes multi-institutional clinical trials as well as investigations involving hemorrhagic shock, organ dysfunction, nutrition, nitric oxide, arginine metabolism, and minimally invasive tissue perfusion measurements. Pediatric Surgery George K. Gittes, M.D. Chief

The Division of Pediatric Surgery, which is currently the only pediatric surgical service in western Pennsylvania, operates through Children’s Hospital of Pittsburgh of UPMC and provides clinical services through the Benedum Pediatric Trauma Program, the Fetal Diagnosis and Treatment Center, and the Nutritional Support Service. Division research is prolific and includes basic and clinical investigations in gut barrier failure, pediatric oncology, pediatric surgical critical care, and pediatric obesity. Plastic Surgery W.P. Andrew Lee, M.D. Chief

The Division of Plastic Surgery offers a spectrum of care for adult and pediatric patients, including surgery to correct body surface defects resulting from trauma or infection, as well as treatment for various pathologic conditions like cancer resections involving the head and neck, breast, skin, and trunk. The division also offers complete cosmetic surgery services. Through Children’s Hospital of Pittsburgh of UPMC, the division treats pediatric plastic surgical

problems, congenital hand deformities, and cleft or craniofacial defects. Research in the division focuses on bone tissue engineering, including the use of bone substitutes; cranial suture biology; and skin flap design and physiology. Surgical Oncology David L. Bartlett, M.D. Chief

The Division of Surgical Oncology offers particular expertise in the surgical treatment of breast cancers, melanomas, sarcomas, upper gastrointestinal malignancies, pancreatic cancers, colorectal cancers, hepatobiliary cancers, and endocrine tumors. Specialized techniques available through the division include sentinel node mapping for breast cancer and melanoma, isolated limb chemoperfusion for arm or leg cancer, peritoneal chemoperfusion for cancers that have advanced into the peritoneal cavity, sphincter-sparing surgery for low rectal cancers, concentrated regional chemotherapy infusion for liver metastases, radio frequency ablation, laparoscopic colon resection, tumor resection, and placement of brachytherapy implants for focused radiation therapy treatments. Division research is aimed at developing novel therapies for cancer and includes a wide array of clinical trials. Thoracic and Foregut Surgery James D. Luketich, M.D. Chief

The Division of Thoracic and Foregut Surgery offers a multidisciplinary approach to noncardiac diseases of the chest. It provides a variety of minimally invasive procedures for esophageal disorders, including gastroesophageal reflux disease, giant paraesophageal hiatal hernias, achalasia, and cancer. The division also performs video-assisted thoracic surgery and other specialized procedures like photodynamic therapy, laparoscopic Nissen fundoplication, laser light-induced fluorescence endoscopy, and laparoscopic-endoscopic

DEPARTMENTS

esophagectomy. Research in the division emphasizes clinical care by redefining options available to patients with esophageal cancer and benign esophageal disorders. Studies have focused on photodynamic therapy for esophageal cancer, minimally invasive esophagectomy, laparoscopic management of giant paraesophageal hernias, and application of molecular diagnostics to staging esophageal cancer. Transplantation Surgery Amadeo Marcos, M.D. Chief

The Division of Transplantation Surgery, which operates through the Thomas E. Starzl Transplantation Institute, has built a worldwide reputation for innovation and excellence in organ transplantation. Much of modern transplant technology was pioneered in Pittsburgh, and this program remains at the forefront not only in liver, intestine, pancreas, and kidney transplants but also in transplant procedures involving pediatric patients. In addition, the institute has done groundbreaking work in pancreatic islet cell transplants and xenotransplantation and has established an innovative procedure to optimize intestinal transplantation. Recent advances have focused on immunosuppressive drug protocols, organ preservation, surgical techniques, pre- and postoperative care, and transplant immunology. Division research covers a wide range of issues, including studies on tolerance, immunotherapy, chimerism, gene therapy, molecular virology, growth factor biology, and bioengineering. Vascular Surgery Michel S. Makaroun, M.D. Chief

The Division of Vascular Surgery provides consultation and surgical intervention for the treatment of aneurysms, atherosclerotic occlusive disease, cerebrovascular disease, thoracic outlet syndrome, and

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various venous and visceral vascular problems. The division works closely with interventional radiology to manage vascular endoluminal imaging for treatment of aneurysms and occlusions. Basic research in the division involves vascular tissue engineering, the effects of nitric oxide on vascular endothelium, biomechanical forces on vascular biology, and pathology using organ culture. Recent clinical investigations have focused on abdominal aortic aneurysms, endografts, and gene therapy. Selected Research Highlights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has demonstrated selective apoptosis induction in cancer cells with minimal toxicity to normal tissues, but not all cancers are sensitive to TRAIL-mediated apoptosis. Yong Jun Lee, Ph.D., and colleagues have observed that pretreatment with acetylsalicylic acid (aspirin) augments TRAIL-induced apoptotis in human prostate adenocarcinoma and human colorectal carcinoma cells. Western blot analysis showed that aspirin pretreatment followed by TRAIL activated caspases and cleaved poly(ADP-ribose) polymerase in tumor cells, confirming that the treatment did, in fact, stimulate apoptosis in these cells. The researchers found that at least 12 hours of aspirin pretreatment was required to promote TRAIL-induced apoptosis and also appeared to down-regulate BCL-2 protein production. Additional studies revealed that BCL-2 protein overexpression suppressed the promotive effect of aspirin on TRAILinduced apoptosis, suggesting that TRAIL works via cellular mitochondria. Based on these results, Lee and colleagues concluded that aspirin-promoted TRAIL cytotoxicity may provide a new therapeutic angle for treating particularly aggressive cancers.

David L. Bartlett, M.D., and colleagues have examined the ability of a vaccinia virus to abolish or significantly inhibit tumor progression in a mouse model of ovarian cancer. The ability of cancer cells to evade apoptosis may permit survival of a recombinant vaccinia lacking antiapoptotic genes in cancer cells compared with normal cells. The researchers inoculated mice with ovarian cancer cells and treated them with cytosine deaminase-encoded vaccinia virus immediately or at 30 or 60 days post-inoculation. The control group was inoculated with cancer cells and received no gene therapy. Bartlett and colleagues observed that immediate gene therapy completely suppressed tumor growth and that therapy provided at 30 and 60 days post-inoculation produced significant tumor inhibition. Mice not receiving gene therapy died from the cancer or its complications. Bartlett and colleagues hope that vaccinia virusbased gene therapy will prove effective in humans because current treatments for ovarian cancer do not provide tumor selectivity and are harsh for patients.

Women who undergo surgery and subsequent radiation treatment for breast cancer often experience breast deformities that require surgical correction. Howard D. Edington, M.D., and colleagues have developed a method to encapsulate the chemotherapeutic agent doxorubicin into biodegradable polymer microspheres, incorporate the microspheres into gelatin scaffolds, and produce a controlled delivery system that also serves as an artificial tissue filler. The researchers found that they could control delivery of the doxorubicin for up to 30 days in a mammary mouse tumor cell line. The chemotherapy-infused gel eradicated tumors in the mouse model. Edington and colleagues plan to develop this compound into a clinical treatment for women facing breast cancer

surgery as a method to reduce the need for radiation and to promote preservation of soft tissue contour following surgery. Minimally invasive epicardial atrial ablation to cure atrial fibrillation currently lacks dedicated technology for intrapericardial navigation around the beating heart. Marco A. Zenati, M.D., and colleagues have developed a novel articulated robotic medical probe for this type of navigation and have performed preliminary experiments in a porcine model. The researchers were able to gain access to the pericardial space and progress around the left atrium without disrupting the beating heart or producing a fatal arrhythmia, unexpected bleeding, or hypotension. Epicardial ablation was successfully performed, and no adverse hemodynamic or electrophysiological events occurred during the trials. Zenati and colleagues conducted tissue examinations following the procedure and observed no injury surrounding the ablation site. Based on this study, the researchers want to improve the curvature radius and proper device visualization for the next generation prototype in hopes of developing a dedicated articulated robotic medical probe for epicardial atrial radiofrequency ablation in humans. David A. Geller, M.D., and colleagues

are studying whether a genetically engineered herpes simplex virus (HSV), the same virus that produces cold sores, can kill liver cancer without harming healthy tissue. The genetically engineered HSV harbors an inactive version of the gene that normally enables the virus to multiply. The gene only becomes active when inside tumor cells, where it causes them to die, thus sparing normal tissue. Geller and colleagues are involved in a clinical trial to test the efficacy of this treatment on colorectal cancer that has spread to the liver.

The gene therapy is designed to improve the response to second-line chemotherapy, which has a current success rate of only 15 to 20 percent. The best treatment for patients with liver cancer, overall, is surgical removal of the tumor tissue and possible transplant. However, in 75 percent of cases, the liver cancer is inoperable at the time of diagnosis. Geller and colleagues hope gene therapy will significantly improve treatment responses when combined with traditional chemotherapy. Because the intestine is especially prone to infection and rejection, patients are normally given several antirejection drugs following intestinal transplants. Kareem M. Abu-Elmagd, M.D., Ph.D., and colleagues have designed a protocol that reduces the amount of antirejection medication needed after intestinal transplant, thus improving quality of life for these patients. The protocol involves administering a one-time, pretransplant dose of either thymoglobulin, which kills and depletes T cells, or alemtuzumab, which depletes both T and B cells. In a trial of the protocol, all patients were given the standard antirejection drug tacrolimus following transplant, but none received steroid supplementation. At 120 days post-surgery, tacrolimus tapering was initiated. While 43 percent of patients exhibited some level of rejection before tacrolimus weaning, the rejection was not chronic. Patients who received alemtuzumab before surgery did slightly better than those treated with thymoglobulin; however, both drugs improved rejection outcomes. The ability to reduce antirejection drug use for intestinal transplants also provides evidence that a reduction protocol is feasible for other abdominal and thoracic transplant procedures.

Institute Thomas E. Starzl Transplantation Institute Amadeo Marcos, M.D. Clinical Director

Fadi G. Lakkis, M.D. Scientific Director

Dr. Samuel P. Harbison Assistant Professorship in Surgery (open) Dr. Mark M. Ravitch Chair in Surgery (open) Thomas E. Starzl Professorship in Transplantation Surgery (open) Charles Gray Watson Professorship in Surgical Education (open)

Regular Faculty Endowed Chairs David L. Bartlett, M.D. Dr. Bernard Fisher Professor

Timothy R. Billiar, M.D. George V. Foster Professor and Chair Harvey S. Borovetz, Ph.D. Robert L. Hardesty Professor and Professor and Chair of Bioengineering, School of Engineering David A. Geller, M.D. Richard L. Simmons Professor George K. Gittes, M.D. Benjamin R. Fisher Professor of Pediatric Surgery David J. Hackam, M.D., Ph.D. Roberta G. Simmons Assistant Professor Brack G. Hattler, M.D., Ph.D. Kathleen DuRoss Ford Professor of Cardiothoracic Transplantation Fadi G. Lakkis, M.D. Frank and Athena Sarris Professor of Transplantation Biology James D. Luketich, M.D. Sampson Family Professor of Thoracic Surgical Oncology George V. Mazariegos, M.D. Jamie Lee Curtis Professor of Pediatric Transplant Surgery Ron Shapiro, M.D. Robert J. Corry Professor of Transplantation Surgery Dr. Henry T. Bahnson Professorship in Cardiothoracic Surgery (open) John J. Fung /Astellas Pharma U.S. Inc. Assistant Professorship in Transplant Surgery (open)

UPMC Pellegrini Chair in Cardiothoracic Surgery (open) University Professor Alan J. Russell, Ph.D. Distinguished Service Professors Bernard Fisher, M.D. Richard L. Simmons, M.D. Thomas E. Starzl, M.D., Ph.D. Distinguished Professor Angus W. Thomson, Ph.D., D.Sc. Professors Kareem M. Abu-Elmagd, M.D., Ph.D. Stephen F. Badylak, M.D., D.V.M., Ph.D. Sally E. Carty, M.D. David K.C. Cooper, M.B.B.S., Ph.D. Peter F. Ferson, M.D. Joerg C. Gerlach, M.D., Ph.D. Anthony M. Harrison, M.D. Robert L. Kormos, M.D. Rodney Jerome Landreneau, M.D. W.P. Andrew Lee, M.D. Yong Jun Lee, Ph.D. Michael T. Lotze, M.D. Michel S. Makaroun, M.D. Ernest K. Manders, M.D. Amadeo Marcos, M.D. J. Wallis Marsh Jr., M.D. Juan Ochoa, M.D. Andrew B. Peitzman, M.D. Wolfgang H. Schraut, M.D., Ph.D. Kenneth C. Shestak, M.D. David L. Steed, M.D. William R. Wagner, Ph.D. Marshall W. Webster, M.D. Norman Wolmark, M.D. Visiting Professors Gabriel Amitai, Ph.D. Mark A. Wilson, M.D., Ph.D. Kenton J. Zehr, M.D.

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Joel B. Nelson, M.D., Dr. Frederic N. Schwentker Professor of Urological Surgery and Chair

Research Professors Jorge A. Genovese, M.D. Marina V. Kameneva, Ph.D. Associate Professors Steven A. Ahrendt, M.D. Anita P. Courcoulas, M.D., M.P.H. Yifan Dai, M.D., Ph.D. Howard D. Edington, M.D. Jie Fan, M.D. Paulo A.C. Fontes, M.D. Chandrashekhar Gandhi, Ph.D. Kenneth K.W. Lee, M.D. Joseph E. Losee, M.D. James M. Lynch, M.D. Victor Onofre Morell, M.D. Noriko N. Murase, M.D. John F. Patzer II, Ph.D. Kun Y. Rhee, M.D. Joshua T. Rubin, M.D. Rakesh Sindhi, M.D. Henkie P. Tan, M.D. Samuel A. Tisherman, M.D. Edith Tzeng, M.D. Yoram Vodovotz, Ph.D. David A. Vorp, Ph.D. Marco A. Zenati, M.D. Visiting Associate Professors Gretchen McGuire Ahrendt, M.D. Robert C. Burns, M.D. Thomas G. Gleason, M.D. Michael Peter Siegenthaler, M.D. Yoshiya Toyoda, M.D., Ph.D. Lawrence Ming Wei, M.D. Research Associate Professors Igor Dvorchik, Ph.D. Rosemary A. Hoffman, Ph.D. Chihiro Koike, M.D., Ph.D. Hongmei Shen, Ph.D. Jennifer E. Woodward, Ph.D. Assistant Professors Miguel F. Alvelo, M.D. Kodi K. Azari, M.D. Amit Basu, M.B.B.S. Philip Michael Bauer Jr., Ph.D. Christian Andres Bermudez, M.D. Deanna Marie Blisard, M.D. Marguerite A. Bonaventura, M.D. Geoffrey J. Bond, M.B.B.S. Charles Kuang Ming Brown, M.D., Ph.D. Rabih Antoine Chaer, M.B.B.S. Sricharan Chalikonda, M.B.B.S. Jae Sung Cho, M.D. Neil A. Christie, M.D. Victoria Terri Lynne Collin, Ph.D. Gregory M. Cooper, Ph.D. Guilherme Costa, M.D.

Carolyn De La Cruz, M.D., M.P.H. Frederic White-Brown Deleyiannis, M.D. Michael T. DeVera, M.D. Ellen Deanne Dillavou, M.D. George Michel Eid, M.D. Farzad Esni, Ph.D. Linda M. Farkas-Pritchard, M.D. Julie Robin Fuchs, M.D. Barbara A. Gaines, M.D. Thomas Clark Gamblin, M.D. Andrea A. Gambotto, M.D. Sebastien Gilbert, M.D. Michael Lawrence Gimbel, M.D. Zong Sheng Guo, Ph.D. Nav-Yash Gupta, M.D. Daniel E. Hall, M.D. Ghassan S. Abu Hamad, M.D. Giselle G. Hamad, M.D. Maryam Feili Hariri, Ph.D. Matthew Holtzman, M.D. Steven J. Hughes, M.D. Shao Jiang, M.D. Ronald R. Johnson, M.D. Pawel Kalinski, M.D., Ph.D. Timothy D. Kane, M.D. Aviva L. Katz, M.D. James William Klena, M.D. Steven A. Leers, M.D. Roberto Carlos Lopez, M.D. Luke K. Marone, M.D. Kacey Gribbin Marra, Ph.D. Carol A. McCloskey, M.D. Kenneth R. McCurry, M.D. Diana M. Metes, M.D. Kelly A. Miller, M.D. Adrian E. Morelli, M.D., Ph.D. Arthur J. Moser, M.D. Jennifer Braemar Ogilvie, M.D. Amit Nikanthkumar Patel, M.D. Daniel P. Pellegrini, M.D. Arjun Pennathur, M.B.B.S. Douglas A. Potoka, M.D. Ramesh Chandran Ramanathan, M.B.B.S. David Anthony Rodeberg, M.D. Matthew R. Rosengart, M.D. Joseph Peter Rubin, M.D. Ulka Sachdev, M.D. Matthew J. Schuchert, M.D. Manisha R. Shende, M.B.B.S. Cynthia A. Smetanka, M.D. Kyle Ansel Soltys, M.D. Jason L. Sperry, M.D. Giovanni Speziali, M.D. Jennifer L. Steel, Ph.D. Detcho Anastassov Stoyanovsky, Ph.D. Vera Svobodova, Ph.D. Kusum Bhikhubhai Tom, M.D. Andrew Rose Watson, M.D.

Peter Drew Wearden, M.D., Ph.D. Ronit Wollstein, M.D. John H. Yim, M.D. Herbert J. Zeh III, M.D. Mazen Zenati, M.D. Brian Scott Zuckerbraun, M.D. Visiting Assistant Professor Raquel M. Forsythe, M.D. Research Assistant Professors Qiang Du, Ph.D. Talal El-Hefnawy, M.D., Ph.D. Nupur N. Gangopadhyay, Ph.D. Thomas W. Gilbert, Ph.D. Jianjun Guan, Ph.D. Ping Guo, M.S. Zhong Guo, M.D. Samuel B. Keeley, M.D. Xiaoyan Liang, M.D. Toshio Miki, M.D., Ph.D. Sanjay K. Mishra, Ph.D. Chandra P. Mullangi, M.B.B.S. Atsunori Nakao, M.D. Alejandro Nieponice, M.D., Ph.D. Julie Anne Phillippi, Ph.D. Petar Jasa Popovic, M.D., Ph.D. Krishna Prasadan, Ph.D. Stefan Schneeberger, M.D. Chiyo Shiota, Ph.D. Chhinder P. Sodhi, Ph.D. Jae Jin Song, Ph.D. Sidhartha S. Tulachan, M.B.B.S., Ph.D. Hiroaki Uchida, M.D., Ph.D. Zhi Liang Wang, M.D. Ziqiu S. Wang, M.D. Youzhong Yuan, M.D. Ruben Zamora, Ph.D. Instructor Douglas Chew, B.S. Research Instructors Pietro Bajona, M.D. Kazuro Lee Fujimoto, M.D. Archana Gangopadhyay, Ph.D. Hidetaka Hara, M.D., Ph.D. Xiaojun Huang, M.D. Qi Li, M.D. Patricia Anne Loughran, Ph.D. Iulia-Dana Popescu, Ph.D. Melanie Jane Scott, M.B.B.Ch., Ph.D. Richard A. Shapiro, B.S. Xiao Hua Shi, M.D. Stijn Vandenberghe, Ph.D.

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DEPARTMENT PROFILE

Zhou Wang, Ph.D., is characterizing

The Department of Urology aims to become a premier center for urologic care and research through outstanding patient care, scientific inquiry, and discovery. Clinical faculty members specialize in prostate cancer, benign prostatic hyperplasia, renal cancer, female urology, and kidney stones. Members of the department also collaborate with colleagues at the University of Pittsburgh Cancer Institute to develop innovative protocols for cancer management. The department’s state-of-the-art research facility at Shadyside Hospital houses research laboratories for neurourology, oncology, transgenic mouse models, tumor biomarkers, gene therapy, and tissue engineering.

androgen receptor (AR) intracellular trafficking in androgen-refractory prostate cancer cells, which are classified by ligand-independent AR internalization. Initial prostate cancer development is dependent on androgens; however, following androgen ablation therapy, androgen-refractory prostate cancer cells remain active, necessitating alternate therapeutic interventions. Because AR nuclear localization is a prerequisite for transcriptional activation, Wang, in collaboration with researchers at the Feinberg School of Medicine at Northwestern University, examined this mechanism in androgenrefractory prostate cancer. The researchers used a green fluorescent protein (GFP)-tagged AR to first confirm that AR internalization in these cells is truly androgen-independent. Then, they observed that the heat shock protein 90 (hsp90) inhibitor, 17-allylamino-17demethoxygeldanamycin (17-AAG), inhibited basal prostate specific antigen expression and disrupted ligandindependent AR nuclear localization. These findings demonstrate that hsp90 is a key regulator of ligandindependent nuclear localization and may provide an appropriate therapeutic target for androgen-refractory prostate cancer cells.

Residency and Fellowship Training

Residencies are available in all aspects of adult and pediatric urology, including urologic oncology, general urology, urodynamics, female urology, reconstructive surgery, endourology, laparoscopy, stone disease, and sexual dysfunction. The department also has a training program for physicians, residents, and scientists in applied basic science research relevant to urologic disease. The overall focus of the training program is on the molecular biology of neuroepithelial function, cancer, and inflammation. Selected Research Highlights

Benign prostatic hyperplasia (BHP), also known as enlarged prostate, affects more than half of men older than 60 and 80 percent of men older than 80. Fifty percent of those with BHP exhibit symptoms, including frequent urination, urinary tract infections, inability to fully empty the bladder, and, in some cases, bladder and kidney damage. Traditional therapies are limited and can cause side effects like impotence. Michael B. Chancellor, M.D., and colleagues have shown that injections of Botox (botulinum toxin A) into the prostate gland of men with BPH relaxes the prostate, thus easing symptoms and improving quality of life. The study, conducted in collaboration with researchers at Chang Gung University College of Medicine in Taiwan, enrolled patients with BPH who did

not respond to traditional therapies. Three-quarters of the patients experienced at least a 30 percent improvement in urinary tract symptoms following Botox injections, with improvements lasting up to one year in some patients; 80 percent of the patients were able to completely empty their bladders within one month after the injection. Dean J. Bacich, Ph.D., and colleagues

study the effect of prostate specific membrane antigen (PSMA), a folate hydrolase, on the stage and grade of prostate cancer. PSMA, which is highly expressed in the normal human prostate, is upregulated in more than 95 percent of prostate cancers. The researchers determined that tumor cells expressing PMSA (LNCaP) experience a growth advantage when cultured in a low folate environment with polyglutamated folates. No such advantage was observed in non-PMSA tumor cells (DU-145). In addition, the PSMAspecific folate hydrolase inhibitor 2-(phosphonomethyl)-pentanedioic acid (2-PMPA) attenuated the increased growth in LNCaP cells but had no effect on DU-145 cells. Bacich and colleagues plan to extend their studies to investigate the role of folate consumption in prostate cancer. Because folate fortification in food has led to a three-fold increase in serum folate levels in the United States since 1998, the researchers wish to confirm whether increased consumption elevates risk.

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Regular Faculty Endowed Chairs Joel B. Nelson, M.D. Dr. Frederic N. Schwentker Professor of Urological Surgery and Chair

UPMC Chair in Urological Research (open) Professors Michael B. Chancellor, M.D. Steven G. Docimo, M.D. Visiting Professors Mark F. Bellinger, M.D. Zhou Wang, Ph.D. Associate Professors Timothy D. Averch, M.D. Ronald L. Hrebinko Jr., M.D. Wendy W. Leng, M.D. Naoki Yoshimura, M.D., Ph.D. Visiting Associate Professors Jeffrey Rae Gingrich, M.D. James R. Gnarra, Ph.D. Stephen V. Jackman, M.D. Francis X. Schneck Jr., M.D. Assistant Professors Dean J. Bacich, Ph.D. Ronald M. Benoit Jr., M.D. Denise Susan O’Keefe, Ph.D. Beth R. Pflug, Ph.D. Hsi-Yang Young Wu, M.D. Visiting Assistant Professors Thomas Michael Jaffe, M.D. Jodi Kathleen Maranchie, M.D. Michael C. Ost, M.D. Jan Pilch, M.D. Changfeng Tai, Ph.D. Pradeep Tyagi, Ph.D. Weihua Zhang, Ph.D. Research Assistant Professor Julie A. Brown, Ph.D.

University of Pittsburgh School of Medicine Administration (As of August 1, 2007)

Arthur S. Levine, M.D. Senior Vice Chancellor for the Health Sciences Dean, School of Medicine Steven L. Kanter, M.D. Vice Dean

Assistant Deans Paula K. Davis, M.A. Assistant Dean for Admissions, Financial Aid, and Diversity Allen L. Humphrey, Ph.D. Assistant Dean for Medical Student Research Rajiv Jain, M.D. Assistant Dean for Veterans Affairs

Charles F. Reynolds III, M.D. Senior Associate Dean

Frank J. Kroboth, M.D. Assistant Dean for Graduate Medical Education

Associate Deans

Cynthia Lance-Jones, Ph.D. Assistant Dean for Medical Student Research

Barbara E. Barnes, M.D., M.S. Associate Dean for Continuing Medical Education Michael L. Boninger, M.D. Associate Dean for Medical Student Research Joan Harvey, M.D. Associate Dean for Student Affairs John P. Horn, Ph.D. Associate Dean for Graduate Studies Joan M. Lakoski, Ph.D. Associate Dean for Postdoctoral Education John F. Mahoney, M.D. Associate Dean for Medical Education Rita M. Patel, M.D. Associate Dean for Graduate Medical Education Beth M. Piraino, M.D. Associate Dean for Admissions and Financial Aid Ann E. Thompson, M.D. Associate Dean for Faculty Affairs Clayton A. Wiley, M.D., Ph.D. Associate Dean for the Medical Scientist Training Program

J.B. McGee, M.D. Assistant Dean for Medical Education Technology Chenits Pettigrew Jr., Ph.D. Assistant Dean for Student Affairs Philip Troen, M.D. Assistant Dean for Medical Student Research

University of Pittsburgh School of Medicine Board of Visitors (As of August 1, 2007) Steven C. Beering, M.D. (Chairman) President Emeritus Purdue University G. Nicholas Beckwith III Chairman and Chief Executive Officer Arch Street Management, LLC Edward J. Benz Jr., M.D. President and Chief Executive Officer Dana Farber Cancer Institute Jordan J. Cohen, M.D. President Emeritus Association of American Medical Colleges Catherine D. DeAngelis, M.D., M.P.H. Editor-in-Chief Journal of the American Medical Association Jonathan D. Gitlin, M.D. Helene B. Roberson Professor of Pediatrics Washington University School of Medicine Antonio M. Gotto Jr., M.D., D.Phil. Stephen and Suzanne Weiss Dean Professor of Medicine Provost for Medical Affairs Joan and Sanford I. Weill Medical College of Cornell University

Michael M.E. Johns, M.D. Chancellor Emory University William K. Lieberman President Lieberman Companies James L. Madara, M.D. Chief Executive Officer University of Chicago Medical Center University Vice President for Medical Affairs Dean, Biological Sciences Division and Pritzker School of Medicine Henry J. Mankin, M.D. Edith M. Ashley Professor of Orthopaedic Surgery Emeritus Harvard Medical School Ross H. Musgrave, M.D. Distinguished Clinical Professor of Surgery University of Pittsburgh School of Medicine Richard E. Raizman, M.D. Clinical Associate Professor of Medicine University of Pittsburgh School of Medicine Medical Director, Specialist Health Care Clinic UPMC Outpatient Services Arthur H. Rubenstein, M.B.B.Ch. Executive Vice President of the University of Pennsylvania for the Health System Dean, School of Medicine Larry J. Shapiro, M.D. Executive Vice Chancellor for Medical Affairs and Dean Washington University School of Medicine Allen M. Spiegel, M.D. Marilyn and Stanley M. Katz Dean Albert Einstein College of Medicine of Yeshiva University Steven A. Wartman, M.D., Ph.D. President Association of Academic Health Centers Savio L.C. Woo, Ph.D. Professor and Chairman Department of Gene and Cell Medicine, Mount Sinai School of Medicine

DEPARTMENTS

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Credits Photographers and Illustrators Peter Arkle, pages 56 – 57 Nicholas Dewar, pages 32 – 33, 68 – 69, 102 – 103 Joshua Franzos, pages 1, 17 (top), 23 (bottom), 27, 37, 38, 40, 41, 72 (middle), 73 (top), 76 – 77 (bottom), 110, 113, 132, 137, 141, 144

Page 80 (bottom): Xenopus laevis oocytes courtesy of Raymond A. Frizzell, Ph.D.; photographed on dissecting microscope at CBI by Donna B. Stolz, Ph.D. Page 81 (top): Danio rerio courtesy of Michael Tsang, Ph.D.; SEM at CBI by Marc Rubin Page 81 (bottom): Caenorhabditis elegans courtesy of Cliff J. Luke, Ph.D.; SEM at CBI by Marc Rubin

DNA Molecules, page 30: “Unwound” by Joe Miksch, February 2006 Bubbles to the Rescue, page 31: “Tiny Bubbles” by Meghan Holohan, August 2005 Honing Skilled Sequential Movements, page 87: “Free-Will Hunting” by Joe Miksch, May 2006 Taming Schizophrenia, page 87: “A Chance for Normalcy? A New Schizophrenia Drug on the Horizon” by Joe Miksch, May 2006

Scott Goldsmith, pages 7, 11, 15

Page 83: Confocal immunofluorescence of actin and CFTR courtesy of Gerard L. Apodaca, Ph.D.

©Warren Jagger Photography, Inc., pages 75 (top and bottom), 76 (top), 78

Page 84: Computer-generated image of CsrA courtesy of Leo Koharudin, Ph.D.

Mechanisms of Memory and Learning, page 88: “Forget It? Timing is Everything When It Comes to Learning and Memory” by Joe Miksch, February 2006

Lynn Johnson, pages 46, 48 – 55

Page 85: Computer-generated image of membrane rotor of V-type ATPase courtesy of Zheng Yang

Responding to Emotional Stimuli, page 89: “Hariri’s Hammer” by Chuck Staresinic, August 2005

Page 87: Aleksey Zaitsev, Ph.D.

A Simultaneous Surprise, page 89: “Calm Down Hurry Up” by Erica Lloyd, August 2005

Jim Judkis, pages 22, 28 Timothy Kucynda, page 90 Cami Mesa, page 88 Annie O’Neill, pages 20 – 21, 30 – 31 (bottom), 39, 58, 60 – 61, 72 (top and bottom), 73 (middle and bottom), 127 Michael Ray, pages 94, 97 Peter Wilson, pages 74 – 75 (middle)

Page 89 (top-face): Ekman, P; Friesen, WV (1976) Page 89 (bottom): Karl Kandler, Ph.D. Page 93: UPMC Creative Services Page 98: UPMC Creative Services Page 101: UPMC Creative Services

Other Photo and Image Credits Page 116 –117: Vincent Lee Page 16 (top): ©2006 National Academy of Sciences, USA, courtesy Tallini, Y.N.; Ohkura, M.; Choi, B-R.; Ji, G.; Imoto, K.; Doran, R.; Lee, J.; Plan, P.; Wilson, J.; Xin, H-B.; Sanbe, A.; Gulick, J.; Mathai, J.; Robbins, J.; Salama, G.; Nakai, J.; Kotlikoff, M.I.; Proc. Natl. Acad. Sci. USA 103, 4753 – 4758. Page 16 (bottom): ©2007 National Academy of Sciences, USA, courtesy Poudyal, M.; Rosa, S.; Powell, A.E.; Moreno, M.; Dellaporta, S.L.; Buss, L.W.; Lakkis, F.G.; Proc. Natl. Acad. Sci. USA 104, 4559 – 4564. Page 17 (bottom): UPMC Creative Services Page 18 (top): Courtesy of Amin B. Kassam, M.D., and Carl H. Snyderman, M.D. Page 18 (bottom): Courtesy of S.C. Watkins and R.D. Salter Page 25 (bottom): Adrian E. Morelli, M.D., Ph.D. Page 29 (top): Association of American Medical Colleges Page 30 (top): Joel M. Harp, Ph.D., Vanderbilt University Page 31 (top): Dina Basalyga, Ph.D. Page 80 (top): Drosophila melanogaster courtesy of Michael J. Palladino, Ph.D.; confocal imaging by Palladino and Adam C. Frank; scanning electron microscopy (SEM) and confocal overlay at Center for Biologic Imaging (CBI) by Marc Rubin

Page 118: Copyright, Pittsburgh Post-Gazette, 2007, all rights reserved. Reprinted with permission.

This report was produced by the Office of Academic Affairs, Health Sciences Margaret C. McDonald, Ph.D. Associate Vice Chancellor for Academic Affairs Stephen J. Byers Director Staff

The information in the following items was abstracted from articles originally published in Pitt Med magazine: Dyeing to See How Hearts Beat, page 16: “To Live and Dye: A Peek at How an Arrhythmia is Wired” by Chuck Staresinic, Spring 2007 Obesity Researcher Looks to Leptin for Answers, page 22: “Gains in Weight Research” by Joe Miksch, May 2006 Potential Therapy for Rare Immunity Defect, page 23: “Bubbles Aside: How Gene Therapy Might Become a Viable Option for a Rare Immune Disease” by Kristin Ohlson, May 2005

Jacqueline Janos, Andrea Lively, Lisa Lorence, Maureen Passmore, Jennifer Petrie-Signore, Ph.D., Cathy Steinitz, and Carol Tatrai Reporting and writing assistance provided by Jim Swyers, UPMC Media Relations. Special production assistance provided by Theresa Ratti, Office of Faculty Affairs, and Tom A. Spanedda, University of Pittsburgh and UPMC Medical and Health Sciences Foundation. Designed by Landesberg Design, Pittsburgh, PA

Workings of the Teenage Brain, page 23: “FBI Calling” by Joe Miksch, Winter 2006 / 07 Exosomes Grab Attention, page 25: “Rodney and Me: Exosomes Get Respect” by Joe Miksch, February 2006 Working Together to Keep Proteins from Aggregating, page 28: “Peculiar Material: Disbanding Unruly Mobs of Proteins” by Jim Swyers, Spring 2007 Amphibian Tales, page 29: “Make Like a Salamander: Limbs on Demand?” by Joe Miksch, Fall 2006

University of Pittsburgh School of Medicine 401 Scaife Hall 3550 Terrace Street Pittsburgh, PA 15261 412-648-8975 www.health.pitt.edu The University of Pittsburgh is an affirmative action, equal opportunity institution.

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