2016 Annual Report UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE OF SCHOOL PITTSBURGH OF UNIVERSITY Adaptation University of Pittsburgh School of Medicine

2016 ANNUAL REPORT

Adaptation

1 Message from the Dean

4 News & Achievements

18 Education & Training

32 Research Grants of Note, 35 Publications of Note, 42

56 Community

65 Donors

76 Administration, Departments, Institutes, & Leadership IT’S IN OUR DNA daptablity is the gift that life’s genetic machinery gives to all living things. We can marvel at it in the natural world, and we can study it in the lab. We can decipher its mechanisms to understand and improve our own health. Finally, we would be wise to design and run our own institutions to be just as doggedly resilient and adaptive, especially at this moment in history. We’re in a time of unprecedented upheaval in science and medi- cine. Scientific advances are transforming the practice of medicine at a dizzying pace. APhysicians enter the profession today knowing that they will offer their patients treatments and diagnostics that were scarcely dreamt of just 20 years ago. As scien- tists, we now have scientific and computational tools to investigate basic biological processes and human health to an extent that was only hinted at with the sequencing of the first human genome in 2003. Even as we embrace these opportunities in science and medicine, we are faced with daunting challenges. Our nation’s much-needed health care reform initiatives are rightfully forcing us to address health care quality, cost, and access. But such reforms limit the ability of academic health centers to support research to the extent that they traditionally have. Meanwhile, federal support of research through the National Institutes of Health (NIH) has, in purchasing power, been stagnant for several years. The most recent NIH data show that the University of Pittsburgh’s NIH funding is on the rise, but it is clear to me that our institution must nonetheless adapt to changing realities.

“ The art of life is a constant readjustment to our surroundings.” KAKUZO OKAKURA

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 1 MESSAGE FROM THE DEAN

In the pages of this report, you’ll learn how we at the University of Pittsburgh School of Medicine remain inventive, innovative, and entrepreneurial in the face of these challenges. We do this through strategic partnerships and through well-­structured, institutional support for developing physicians and scientists. We commit our resources to emerging areas of biomedical research, and we focus on the translation of basic science discoveries to clinical care. To give just a few examples:

• Pitt’s new Center for Medicine and the Microbiome earned top billing at a March 2016 White House event announcing the launch of the National Microbiome ­Initiative. This important project aims to improve our understanding of the t­rillions of microbes that exist throughout the human body and make major contributions to our health and physiology. These insights hold tantalizing promise for improving human health.

• In July 2016, Pitt’s Clinical and Translational Science Institute was awarded a trans- formative $53 million grant under the NIH’s Precision Medicine Initiative Cohort Program. One of the first such awards in the nation, it makes Pitt a key player in the nationwide effort to enroll and sequence the genomes of 1 million volunteers to dramatically expand the base of knowledge that allows us to personalize medical treatments based on genomic information.

In the educational arena, our medical students learn in year one that our cur­ riculum is, by necessity, supremely adaptive. They are invited to participate as faculty, staff, and students evaluate the curriculum in light of our evolving understanding of science and the changing practice of medicine. By the time they graduate, our students have witnessed and helped to guide important changes in the teaching of certain subjects as our knowledge grows deeper and more nuanced. What never changes is that we are fully committed to preparing our students to be skilled, science-based, compassionate clinicians and innovative biomedical scientists. Those are the qualities that enable us to adapt to any state of affairs. I invite you to discover for yourself how the University of Pittsburgh School of Medicine fulfills that commitment on the pages of this report.

ARTHUR S. LEVINE, MD Senior Vice Chancellor for the Health Sciences and John and Gertrude Petersen Dean of Medicine

2 Our Shared Ancestry

“UPMC was created out of the University of Pittsburgh (and) the two have risen together in national and international prestige,” Pittsburgh-area historian and NIH author Mary Brignano notes in Beyond the Bounds: A History of UPMC. “UPMC’s RANKING founders followed one core principle: In the only truly objective metric Research and clinical success are synergistic and inter­dependent. What by which the overall stature of is good for one is good for both.” research-focused institutions The visionary spirit of those early can be assessed in a nationally leaders has continued through to today, competitive context, the Univer- more than 40 years after the great sity of Pittsburgh moved into “Pittsburgh experiment” began. Much the TOP 10 list of recipients of about the region’s landscape has changed National Institutes of Health over the decades, with education and (NIH) funding in 1998. In recent health care assuming the economic decades, there have been very pride-of-place once reserved for heavy few newcomers among this elite industry. Together, the University group of institutions; Pitt not only and UPMC have grown into one of the cracked the top 10 but steadily nation’s leading academic medical rose over the ensuing years to centers, medical schools, and training the extent that it is now firmly grounds for physicians, scientists, anchored in the heart of this and other health care professionals. enviable echelon that comprises We proudly continue to serve the people the nation’s leading research of our community—delivering superb institutions. In fiscal year 2015, care to neighborhoods throughout the Pitt faculty received more than region and across the country. $475 million in total funding, with Today, Pitt and UPMC’s vital the lion’s share of that funding collaboration still drives a circular bond going to the School of Medicine. from research to clinical care, and back to research—but now, it’s moved forward from transforming Pittsburgh to transforming health sciences education and clinical care across the globe.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 3 NEWS & ACHIEVEMENTS MAJOR INITIATIVES

NEWS & ACHIEVEMENTS

Research Partici­pant Registry of more than 103,000 participants as well Pitt Is Key Player in NIH-Funded Million-Person as an additional 165,000 individuals over the five-year award period. Precision Medicine Study “This project is a testament to the strength and value of the integrated research resources and expertise we’ve been able to build through CTSI over the past 10 years at Pitt,” said principal investigator Steven E. Reis, FIVE-YEAR PITT AWARD EXPECTED TO TOTAL $46 MILLION MD, associate vice chancellor for clinical research, health sciences, Distinguished Service Professor of Medicine, and CTSI director. “The n early July 2016, the National Institutes of Health (NIH) released PMI Cohort Program will provide individuals from across the region, $55 million, with $4.2 million of that awarded to the University of and the nation, with an unprecedented opportunity to contribute to the Pittsburgh, to build the foundational partnerships and infrastructure development of individualized approaches to prevent and treat disease. needed to launch the Cohort Program of President Obama’s Preci- What we learn now by working together will benefit ourc­ hildren, grand- Ision Medicine Initiative (PMI). The PMI Cohort Program is a landmark children, and generations to come.” longitudinal research effort announced in the 2015 State of the Union “Every patient is different; every patient has a unique story. This address that aims to engage 1 million or more research participants comprehensive massive collection of patient information, combined across the country to revolutionize how disease is prevented and treated with our advanced analytics approach eventually will enable us to treat based on individual differences in lifestyle, environment, and genetics. each patient in a personalized way to produce the best possible results,” Over five years, the total amount awarded to Pitt is expected to top said Steven D. Shapiro, MD, UPMC’s chief medical and scientific officer. $46 million, pending progress and availability of funds. Pitt is one of PMI Cohort Program volunteers will be asked to contribute a wide four organizations receiving awards to support a network of Healthcare range of health, environment, and lifestyle information. They also will Provider Organizations (HPO)—the others being Columbia University be invited to answer questions about their health history and status, Health Sciences, Northwestern University, and the University of Arizona. share their genomic and other biological information through simple The awards set the NIH on course to begin initial enrollment into the blood and urine tests, and grant access to their clinical data from elec- PMI Cohort Program during 2016, with the aim of meeting its 1 million tronic health records. person enrollment goal by 2020. In addition, mobile health devices and apps will provide lifestyle data “As an HPO, the University of Pittsburgh, in collaboration with UPMC and environmental exposures in real time. All of this data acquisition (University of Pittsburgh Medical Center), has an essential role in the PMI Cohort Program, one of the National Institutes of Health’s most ambi- tious research efforts since the Human Genome Project,” noted med school dean Arthur S. Levine, MD. “We are on the cusp of a new era in medicine in which we can apply knowledge in genetics and genomics, combined with lifestyle and environmental data and other disciplines, to improve disease prevention strategies and tailor treatment options for everyone,” he added. Led by Pitt’s Clinical and Translational Science Institute (CTSI)—a collaboration of the University of Pittsburgh Schools of the Health Sciences and UPMC—the Pitt PMI project, called the Precision Approach to healthCARE (PA CARES), is being launched at 11 enrollment sites across the western half of Pennsyl­vania and neighboring states. In its first year,PA CARES aims to recruit and enroll 10,000 volunteer participants, primarily from CTSI’s

4 will be accomplished with essential privacy and security safeguards. trained 850 investigators and supported more than 2,000 investigators As partners in the research, participants will have ongoing input into who have conducted more than 4,000 research studies. study design and implementation, as well as access to a wide range of “Among our most important goals for the next five years is engag- their individual and aggregated study results. ing a broader range of people and communities in research,” said CTSI Nearly 50 jobs will be created across Pennsylvania as a result director Steven E. Reis, who is also associate vice chancellor for ­clinical of this grant, in patient recruitment, data collection, and process- research, health sciences, and a professor of medicine. “We will also ing. Indi­viduals wishing to enroll in the CTSI registry may do so at expand CTSI’s reach by launching several new programs, including a www.researchregistry.pitt.edu. focus on entrepreneurship in research and in translating discoveries to practice.”

New initiatives during the upcoming grant period include: • Innovation as a Discipline Pitt Receives $62.3 Million, Five-Year NIH Award • Biomedical Modeling To Accelerate Translational Scientific Research into • Integrating Special Populations Implementable Solutions • Clinical Trial Recruitment and Efficiency • Clinical Trial Innovation • Multidisciplinary Team Science he University of Pittsburgh Clinical and Translational Science Institute (CTSI) will receive nearly $62.3 million over five years Funding is being provided through NIH’s National Center for Advancing from the National Institutes of Health (NIH) to broaden its Translational Sciences. mission of speeding translation of scientific research into real- Tistic treatments for the people who need them. In 2006, CTSI was among the first12 recipients of NIH’s Clinical and Translational Science Awards (CTSA). Since then, Pitt’s CTSA funding has totaled more than $221 million. Including the recently announced fund- Welcome to the West Wing ing for Pitt’s participation in NIH’s Precision Medicine Initiative Cohort SEE THE FUTURE OF PITT MED Program, CTSI-supported programs have been awarded approximately $108 million in research funding over the next five years. ince the 1950s, Scaife Hall has served as the hub of medical “This award is emblematic of the significant contribution that Univer- education on Pitt’s campus. Directly connected to UPMC Presby­ sity of Pittsburgh researchers and physicians are continuing to make to terian and Montefiore Hospitals, not to mention research facil- advance our understanding of biomedical science and improve clinical ities in Biomedical Science Tower 3 and the Thomas E. Starzl care,” said Arthur S. Levine, MD, Pitt’s senior vice chancellor for the Biomedical Science Tower, Scaife Hall’s educational and research health sciences and John and Gertrude Petersen Dean of Medicine. Sfacilities have been modernized many times over the years. But those Over the past 10 years, CTSI has built an infrastructure of program- improvements don’t even come close to the blockbuster expansion ming to support all avenues of scientific investigation, from guidance in that planners and architects now envision for the School of Medicine. regulatory requirements and study design to career/workforce devel- While the plans are still in development and have hurdles to clear opment, education and training, community engagement, biomedical before the first med student crosses the threshold, the School of informatics, pilot funding of early-stage research, and innovation. It has Medicine envisions a new west wing with more than 200,000 square feet dedicated to medical education. Students would be the chief benefi- ciaries of the seven-story expansion. The glass entry, high ceilings, lime- stone and wood surfaces, and open spaces will make for a welcoming atmosphere filled with natural light. New learning environments will be state of the art, with technology fully integrated into the design. These include a top-floor anatomy lab, a team-based learning room, and a dividable lecture hall that reuses the original wood from Scaife’s stately lecture rooms. This major, multiphase project is expected to create an unparal- leled destination for medical education. While planners wait for the word “Go!“ on the major expansion, a $4.5 million renovation centered on the fifth floor of Scaife Hall is already approved. It, too, is focused on improving student services and student facilities, and it will pave the way for the complete west wing overhaul to come.

A FUTURISTIC VIEW OF SCAIFE HALL

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 5 NEWS & ACHIEVEMENTS LEADERSHIP

New Chairs Named for Departments of Ophthalmology, Physical Medicine and Rehabilitation, and Pediatrics

as founding director of Paris’ Vision Institute, a translational research Pitt Recruits Prominent Physician-Scientists center housing 320 investigators and staff focused on understand- ing vision and finding therapies for currently untreatable genetic and age-related eye diseases. Areas of research interest for Sahel include investigations of the he School of Medicine has been able to tempt top cellular and molecular mechanisms associated with retinal degeneration biomedical scientists to call Pittsburgh home more (particularly genetic rod-cone dystrophies), as well as developing and than once over its 130-year history. Now, 2016 brings evaluating innovative treatments for retinal diseases using pharmacologic a trifecta of exceptionally stellar talent to Pitt — both approaches, prosthetics, optogenetics, gene therapy, and stem cells. homegrown and recruited. In milestone work, Sahel and his collaborators discovered rod-derived One of the world’s foremost clinician-scientists cone viability factor (RdCVF), a protein secreted in the normal retina in vision research, José-Alain Sahel, MD, joined that protects cone photoreceptors. This finding provided the biological the faculty on July 1 as Eye and Ear Foundation Professor and chair of basis for paracrine interactions between rods and cones, which, the Sahel Tophthalmology. team demonstrated, play a critical role in maintaining photo­receptor cell “José-Alain Sahel is a gifted scientist whose transcendent goal is viability. RdCVF has been shown to preserve central vision in several to apply the results of research to patient care with immediacy,” said models of genetic human diseases causing blindness. His laboratory has dean Arthur S. Levine, MD. “I believe his influence here will have great also conducted research on the development of high-resolution in vivo institutional impact.” cellular imaging, relevant biomarkers, and disease models. Sahel has been recruited to the University from Paris, where he served In addition, he is a co-inventor on more than 20 patents, several of as professor of ophthalmology at the Université Pierre-et-Marie-Curie, which formed the basis of start-up companies, including the Sahel- the medical school of the Sorbonne. He is also chair of departments founded Fovéa Pharmaceuticals, which later became an ophthalmo- of ophthalmology in the largest eye hospitals in the country, as well logic division of Sanofi-Aventis. He is also scientific cofounder of several

6 companies, including GenSight Biologics S.A., a company focusing on gene therapy-based approaches to treat mitochondrial and neuro­ degenerative diseases of the eye and central nervous system, and Pixium Vision, which develops innovative bionic vision restoration systems. Gwendolyn Sowa, MD, PhD, newly named Physical Medicine and Rehabilitation Professor and department chair, formerly served as associ- ate professor of physical medicine and rehabilitation and of orthopaedic surgery (School of Medicine) and of bioengineering (Swanson School of Engineering). She succeeds Michael L. Boninger, MD, who has taken on an administrative role as vice president for medical affairs forUPMC ’s Division of Community Provider Services, the umbrella organization that manages all community-based and post-acute clinical programs. Sowa also serves as associate dean for medical student research, ­codirector of the Ferguson Laboratory for Orthopaedic and Spine Research, and medical director of UPMC Total Care — Musculoskeletal Health. She is also an associate editor for PM&R, the official journal of the American Academy of Physical Medicine and Rehabilitation, and serves on the board of trustees of the Association of Academic Physiatrists. Sowa completed her PhD in biochemistry and MD at the University of Wisconsin–Madison, and her physical medicine and rehabilitation (PM&R) residency at the Rehabilitation Institute of Chicago, North- western University. A PM&R clinician-scientist for more than 10 years, she has been active in developing new models of care, assessment of patient-reported outcomes, and interdisciplinary work groups to improve care quality. In particular, she has encouraged multidisciplinary collab- oration to enhance treatment for patients with low back pain. Sowa is also a noted educator, mentoring more than 65 trainees— more than half of whom have received awards for their research. Her research interests have focused on the effects of mechanical loading on musculoskeletal tissues and targeted biomarker discovery to inform the development of individualized treatment programs for low back pain — the most common cause of global disability. “Dr. Sowa’s many accomplishments demonstrate her ability to cross specialties and to collaborate effectively in the clinical, research, and educational arenas. She is the definition of a committed teacher and mentor,” said Levine. Terence S. Dermody, MD, has been appointed the Vira I. Heinz Professor and chair of pediatrics, physician-in-chief at Children’s ­Hospital of Pittsburgh of UPMC, and scientific director of the Rangos Research Center. He was recruited from Vanderbilt University School of ­Medicine, where he served as the Dorothy Overall Wells Professor of Pediatrics and director of both the Division of Pediatric Infectious Diseases and the Medical Scientist Training Program. Dermody is a virologist with interests in viral pathogenesis and vaccine development. He has focused mainly on reovirus, an ­important experimental model for studies of viral encephalitis in infants, and on chikungunya virus, an arthropod-borne virus that causes epidemics of febrile arthritis. He received his MD from Columbia University, interned at New York-Presbyterian Hospital, and completed infectious diseases and molecular virology fellowships at Brigham and Women’s Hospital and Harvard Medical School. “His academic interests, which included running Vanderbilt’s­ MD/PhD training program, are unusually broad,” noted Levine. “An exceptional physician and scientist, he will be an asset to our faculty, residents, and students.” In addition to his own NIH-supported virology research, Dermody’s priorities at Children’s include addressing autism, childhood cancers, and the so-called “social determinants” of health — the many socio­economic and related factors that influence diet, lifestyle, and quality of life.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 7 NEWS & ACHIEVEMENTS FRIENDS IN HIGH PLACES

Innovative Pitt Projects Funded by Pittsburgh Health Data Alliance New Faces

mong the first projects to be funded by the Pittsburgh Health Data Alliance are several Pitt-led innovations developed through Welcome to Your New Faculty Orientation the University’s Center for Commercial Applications of Health- care Data (CCA), an initiative led by Michael J. Becich, MD, PhD, ADistinguished Professor and chair of biomedical informatics. Launched in March 2015, the Pittsburgh Health Data Alliance is a ew faces bring a special energy to the School of unique collaboration involving UPMC, the University of Pittsburgh, and Medicine, which, according to recent data, tallies Carnegie Mellon University with a focus on building new companies 31 departments and more than 4,700 full-time that create data-intensive software and services to potentially revolu- and volunteer faculty members. Among notable tionize health care and wellness. Nnew faculty members recruited to the School of Medicine With this infusion of funding, four teams of University of Pittsburgh during the past year are: researchers now have the resources to advance their technologies aimed at reducing patient falls, preventing and monitoring pressure ulcers, improving the accuracy of cancer diagnoses, and providing Nathan Urban, PhD, is professor and personalized treatment recommendations. UPMC’s funding for these vice chair of neurobiology, vice provost innovations is expected to total more than $3 million as the commer- for special projects, associate director of cial potential of these products is further explored. the University of Pittsburgh Brain Institute, and codirector of the joint Pitt-Carnegie FUNDED CCA PROJECTS ARE: Mellon University Center for the Neural The Tumor-Specific Driver Identification (TDI) System is a software Basis of Cognition. Urban received a PhD in package that will provide personalized genomic information to cancer neuroscience from the University of Pitts- clinicians about the genetic drivers of an individual patient’s tumors. burgh and completed a postdoctoral fellowship at the Max The TDI algorithm will be used for real-time mining of genetic “big data” Planck Institute for Medical Research in Germany, where that will enable personalized treatments for cancer patients. TDI also his mentor was Nobel Laureate Bert Sakmann, PhD. Among is expected to lead to the discovery of new cancer drivers and may be his research interests are physiological and computational used by pharmaceutical companies to identify novel drugs. Investiga- analyses of neural circuit function and the development tors on this project are Xinghua Lu, MD, PhD, professor, and Gregory F. and application of physiological and optical techniques to Cooper, MD, PhD, professor and vice chair, both of the Department of facilitate studies, including of the olfactory bulb. In his role Biomedical Informatics. in the provost’s office, Urban will be involved in supporting the development and promotion of University-wide strategic Fall Sentinel, led by Richard D. Boyce, PhD, assistant professor of initiatives in neuroscience research and education. biomedical informatics, is an automated system that will make it possi- ble for clinical pharmacists to continuously monitor patients in nursing homes, especially for potential multidrug interactions that might lead to Don Taylor, PhD, MBA, is assistant vice falls. Nursing home falls are one of the most common and dangerous chancellor for commercial translation in events for patients, with treatment costing the nation’s health system the health visiting sciences; visiting asso- more than $4 billion each year. ciate professor of biomedical informatics The Pressure Ulcer Monitoring Program is an approach to reducing and of plastic surgery, School of Medicine; hospital-acquired pressure ulcers, a condition that affects an estimated and associate professor of bioengineer- 3 million patients annually. The monitoring and alert solutions, using ing, Swanson School of Engineering. Taylor wearable devices and hospital bed sensors, will provide real-time docu- received his PhD in bioengineering from mentation of patient repositioning and a process to improve compliance the Swanson School of Engineering at the University of with these preventive measures. J. Peter Rubin, MD, UPMC Professor Pittsburgh and an MBA from the Joseph M. Katz Graduate and chair of plastic surgery, is spearheading this effort. School of Business. A longtime life sciences entrep­ reneur, Taylor recently served as CEO of health­Stratica LLC and as SPDx (Spatial Pathology Powers Cancer Diagnosis) is a software program an executive-in-residence at the Pittsburgh Life Sciences that will aid pathologists in delivering more accurate diagnoses from Greenhouse. His responsibilities include working across the complex tumor images. Initially, the focus is on breast cancers, in which six health sciences schools to accelerate commercial trans- misdiagnosis can have deadly consequences. The principal investigators lation of Pitt’s discoveries and inventions, in concert with are Chakra Chennubhotla, PhD, associate professor of computational the Innovation Institute, Clinical and Translational Science and systems biology, and D. Lansing Taylor, PhD, Allegheny F­ oundation Institute, and University administration. Taylor also ­codirects Professor of Computational and Systems Biology and director of the the Center for Commercial Applications of Healthcare Data University of Pittsburgh Drug Discovery Institute. under the Pittsburgh Health Data Alliance Initiative and is associate director of the Center for Medical Innovation at the University of Pittsburgh.

8 University and his PhD in chemistry at Harvard Whitehead Institute. “His broad scientific University. “Effective communication of results, perspective and passionate advocacy for basic as well as key aspects of the scientific process research, combined with his interest in scien- and culture, has never been more important,” tific policy, makes him a superb spokesperson said Berg, who leads the author team for the for the scientific community.” textbook Biochemistry, first written by Lubert Berg’s research has focused on the relation- Stryer. ships between the structures and functions “Science magazine is a huge voice and plays an of biological molecules. More specifically, he outsized role in matters of policy and all things has made major contributions to understand- associated with the pursuit of new knowledge ing how zinc-containing proteins bind to DNA and scientific advances,” said Pitt Chancellor or RNA and regulate gene activity. His work, Patrick Gallagher. “We are proud of Jeremy, along with the contributions of others in the who has been a contributor at the national field, has led to the design of metal-contain- level for many years.” ing proteins that control the activity of specific Berg, a former president of the American genes. Berg has also made contributions to the Society for Biochemistry and Molecular Biology, understanding of systems that target proteins is widely regarded as an effective and accom- to specific compartments within cells, and to Pitt’s Jeremy Berg Named plished leader during his tenure as NIGMS direc- the use of sequence databases for predict- Top Editor at Science tor and his various University roles. Communi- ing aspects of protein structure and function. cations have always been a critical part of his Within the scientific community, he is perhaps JOURNAL LEADERSHIP IS AMONG leadership style, including scientific analysis most widely known for his work on zinc finger THE MOST PRESTIGIOUS EDITORIAL and viewpoints shared in his regular NIGMS proteins, including the successful prediction of POSTS IN THE FIELD / BONUS: director’s and Datahound blogs. the three-dimensional structure of TFIIIA-type BERG WILL REMAIN ON PITT FACULTY Berg will remain in his roles at Pitt, said zinc finger domains prior to the experimental Arthur S. Levine, MD, senior vice chancellor determination of their structures. Currently, he eremy M. Berg, PhD, associate senior for the health sciences and John and Gertrude is using computational methods to estimate vice chancellor for science strategy Petersen Dean of Medicine. binding free energies for peptides interacting and planning, health sciences, and a “Dr. Berg is one of the nation’s leading scien- with targeting receptors. former director of the National Insti- tists, with many landmark achievements in Founded in 1880 with seed money from tute of General Medical Sciences at biomedical research, a broad and deep sense Thomas A. Edison, Science has been the official the National Institutes of Health (NIH), of all of the sciences, and a profound interest in journal of the nonprofitAAAS since 1900. The has been named editor-in-chief of the science policy and the dynamics of the scientific Science family of journals includes Science, Science Science family of journals by the Board of community,” said Levine. “I am proud indeed Translational Medicine, Science Signaling, the JDirectors of the American Association for the that Dr. Berg has been given this rare recog- open-access journal Science Advances, Science Advancement of Science (AAAS). He officially nition, and especially proud that he is, and will Robotics, and Science Immunology. began the journals’ top editorship on July 1, 2016. remain, a member of our faculty.” Berg, professor of computational and Gerald R. Fink, PhD, immediate past presi- systems biology and professor of chemistry dent of AAAS and chair of the search committee at the University of Pittsburgh, becomes the that unanimously selected Berg, commended 20th editor in chief of Science since the journal’s the decision. “Our committee felt that Jeremy inception in 1880. He will serve a five-year term. Berg was a terrific choice among a group of “I am thrilled and humbled by the oppor- excellent candidates,” said Fink, who is the tunity to work with the team at Science and Margaret and Herman Sokol Professor and AAAS,” said Berg, who earned his bachelor’s American Cancer Society Professor of Genetics and master’s degrees in chemistry at S­ tanford at the Massachusetts Institute of Technology/

“Science magazine is a huge voice and plays an outsized role in matters of policy and all things associated with the pursuit of new knowledge and scientific advances.”

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 9 NEWS & ACHIEVEMENTS PROFESSIONAL AND SCIENTIFIC EXCELLENCE

AAP / ASCI

Prestigious Societies Elect Pitt Experts

ive School of Medicine faculty mem- bers have been tapped to join the prestigious Association of American Physicians (AAP) and the American FSociety for Clinical Investigation (ASCI). Induc- tion into these societies is considered among the h­ ighest honors in biomedical science. New AAP members are David Brent, MD, Professor of Suicide Studies, of psychiatry, and of pediatrics, School of Medicine, and professor of epidemiology, Graduate School of Public Health; Anne B. Newman, MD, MPH, ­Katherine M. Detre Professor of Population Health Sciences and professor and chair of epidemiology, Graduate School of Public Health, and professor of medicine and of clinical and translational science; and Brian Zuckerbraun, MD, Henry T. Bahnson Professor of Surgery. Founded in 1885, AAP is dedicated to the pursuit of medical knowledge, experimenta- tion and discovery in basic and clinical science, and the application of new findings to clinical medicine. Each year, 60 people are chosen for AAP membership. ASCI inductees are Stephen Chan, MD, PhD, visiting associate professor of medicine and director of the Center for Pulmonary Vascu- CLOCKWISE lar Biology and Medicine at Pitt’s Vascular FROM TOP LEFT: BRENT, NEWMAN, Medicine Institute; and Bernhard­ Kühn, MD, CHAN, KÜHN, AND associate professor of pediatrics and of cell ZUCKERBRAUN biology, Richard King Mellon Institute for Pedi- atric Research scholar, and director of research, Division of Pediatric Cardiology. The two join 51 other Pitt colleagues on the membership rolls of ASCI, an organization of more than 2,800 physician-scientists who have achieved notable success relatively early in their careers. Founded in 1908, ASCI is a medical honor society with a clear preference for ­celebrating up-and-coming scholarly achievement in biomedical research. New members must be 50 or younger at the time of their election.

10 Strick Joins PNAS Editorial Board Elite Journal Honors Pitt Partner in China

TSINGHUA UNIVERSITY’S YIGONG SHI, PHD, eter L. Strick, PhD, Thomas Detre Professor of Neurosci- RECOGNIZED FOR MENTORSHIP ence, Distinguished Professor and chair of the Department of Neurobiology, has been named to the systems neuroscience he School of Medicine congratulates a section of the Proceedings of the National Academy of Sciences key figure in its Pitt-Tsinghua University P(PNAS) editorial board. Strick, a leading expert on the neural basis of partnership, Yigong Shi, PhD, vice pres- movement and cognition, is director of Pitt’s Brain Institute and was ident of Tsinghua University and dean elected to membership in the National Academy of Sciences in 2012. Tof Tsinghua’s School of Life Sciences, who has He joins Angela M. Gronenborn, PhD, UPMC Rosalind Franklin received the 2015 Nature Award for ­Mentoring Professor, Distinguished Professor and chair of the Department of in Science. Held annually, each Nature-hosted Structural Biology, who is an editorial board member of the biophysics awards ceremony focuses on a specific country and computational biology section at PNAS. or countries and seeks to champion the impor- PNAS is one of the world’s most-cited and comprehensive multidisci- tance of mentor­ing and inspiring young scientists. plinary scientific journals, publishing more than3 ,800 research papers The 49-year-old Shi received the journal’s mid-career award in annually that span the biological, physical, and social sciences. Northern China, along with a prize of 50,000 yuan. Shi is a world leader in the structural biology of cell signaling and macromolecular assem- blies. He is known for demonstrating the first three-dimensional struc- ture of an intact yeast spliceosome at a resolution of 3.6 angstroms, a landmark achievement that increases the mechanistic understanding Center for Medicine and the Microbiome Launched of pre-messenger RNA splicing. His team uses the tools of structural biology to elucidate the functional mechanisms of several key classes PITT HEALTH SCIENCES AND UPMC ESTABLISH JOINT VENTURE of proteins that control apoptosis, or programmed cell death. Apoptosis plays essential roles in the development of multicellular organisms and ur bodies host a vast ecosystem, with microbes ­far outnumber­ in preventing diseases like cancer and autoimmune disorders. ing human cells. They assist in digestion, fight off disease, Beginning in 2012, medical and graduate students from Tsinghua produce vitamins, and otherwise partner with us in a ­symbiotic University have come to Pittsburgh to participate in a two-year training tango of life. Some, though, may increase our risk for diseases program in biomedical research. To date, 67 scholars have completed Oor flat out make us sick. their School of Medicine training and returned to Tsinghua University. Pitt’s new Center for Medicine and the Microbiome is bringing together scientists and clinicians to explore how the microbiome affects health and disease — and how it can be harnessed to develop new therapies to help patients. The initiative aims to advance the understanding of Honors for Burns, Tan microbiome behavior and enable protection and restoration of healthy microbiome function, including investigations of fundamental principles that govern microbiomes across diverse ecosystems and development of new tools to study microbiomes. imothy F. Burns, MD, PhD, assistant professor of ­medicine “The very nature of the microbiome involves many organs and affects in the Division of Hematology/Oncology, and Roderick many areas of medicine — from infectious disease, to cancer biology, J. Tan, MD, PhD, assistant professor of medicine in the to inflammatory bowel disease, to immunology — requiring collabora- ­Division of Renal-Electrolyte, have received the 2016 Young tion between the many disciplines of science and medicine, something T­Physician-Scientist Award from the American Society for Clinical UPMC and Pitt have a proven track record of achieving,” said Mark T. Investigation. Gladwin, MD, Jack D. Myers Professor, Distinguished Professor and Burns studies ways to develop therapies for non-small cell lung cancer chair of Pitt’s Department of Medicine. targeting the KRAS mutant oncogene, and Tan studies the molecular The center is being led by Alison Morris, MD, MS, UPMC Professor mechanisms underlying both acute kidney injury and chronic kidney of Translational Pulmonary and Critical Care Medicine in the Department disease and fibrosis. of Medicine, and Barbara Methé, PhD, visiting professor of medicine and former professor at the J. Craig Venter Institute. “There is a lot of enthusiasm on campus,” said Morris, adding that a project to analyze the oral microbiome is currently ongoing in collabora­ tion with Alexandre Vieira, DDS, MS, PhD, professor of oral biology and director of clinical research, School of Dental Medicine. Vieira is also principal investigator of the school’s Dental Registry and DNA ­Repository, a collection of some 3,500 saliva samples and dental pheno- types matched with DNA and clinical health data. Other collaborations include fecal transplant research with John Mellors, MD, professor of medicine, Global Elimination of HIV and AIDS professor, and chief, Division of Infectious Diseases, and Tatiana Bogdanovich, MD, PhD, MSc, clinical assistant professor of medicine in the infectious diseases division, as well as commercial application projects with UPMC Enterprises.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 11 NEWS & ACHIEVEMENTS WHITE HOUSE WELCOMES GOLDSTEIN

ABOVE, LEFT ARROW, TINA GOLDSTEIN, CENTER ARROW, PRESIDENT OBAMA

12 Goldstein Receives Presidential Honor

t isn’t every day you suit up for a photo op in the East Room of the White House with the leader of the free world and formal, full-length portraits of George Iand Martha Washington on the wall for company. But that’s just what happened to Tina ­Goldstein, PhD, associate professor of psychi- atry, in May, when she and other top talent in research gathered in the nation’s capital to receive 2016 Presidential Early Career Awards for Scientists and Engineers, the highest honor given by the U.S. government to science and engineering professionals who are in the initial stages of independent research careers. Goldstein joined the Pitt faculty in 2006 after completing a psychology internship and postdoctoral fellowship in child and adolescent psychiatry at Western Psychiat- ric Institute and Clinic of UPMC. She received her PhD in clinical psychology from the University of Colorado, Boulder. Goldstein’s work focuses on the assess- ment and psychosocial treatment of young people who have or are at risk for bipolar disorder, with a particular interest in suicide prevention. She aims to develop improved prevention and intervention strategies for young people informed by an enhanced understanding of the complex relationship between biological and psychosocial deter- minants of mood disorder and suicide. She is principal investigator for National Institute of Mental Health-funded grants to study early assessment and intervention and improving medication adherence among adolescents with bipolar disorder. Goldstein has widely disseminated her work, collaborating on more than 60 peer- review publications in high-impact journals, including The American Journal of Psychiatry, Journal of the American Academy of Child & Adolescent Psychiatry, and Archives of General Psychiatry, as well as numerous book chapters, and is coauthor of a book on the treatment of depressed and suicidal youth. Established by President Bill Clinton in 1996, the Presidential Early Career Award honorees are selected for their pursuit of studies at the frontiers of science and their commitment to community service through scientific leadership, public education, and outreach.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 13 NEWS & ACHIEVEMENTS HONORS AND CELEBRATIONS

A Commendation for Kochanek

atrick M. Kochanek, MD, Ake N. Grenvik Professor of C­ ritical Care Medicine, has been selected to receive a Lifetime Achieve- ment Award from the American College of Critical Care Medicine. The organization’s highest award, which recog- Pnizes “pioneering contributions to the field of critical care through the advancement of medical science, medical education, and medical care,” will be presented at the 46th Congress of the Society of Critical Care Medicine in January 2017. A 2014 special report by ScienceWatch called Kochanek “the most prolific of authors” on traumatic brain injury (TBI), noting that he had contributed to 300 reports, which had generated more than 3,800 citations. He has a long track-record of investigation in traumatic and ischemic brain injury and neurointensive care and is funded by the U.S. Army, National Institutes of Health, and the Laerdal Foundation. “This is a reflection of the hard work and dedication of the entire team involved in pediatric critical care,” said Kochanek, who is vice chair of critical care medicine, professor pediatrics and of clinical and translational science, and professor of bioengineering, Swanson School of Engineering. Kochanek received his MD from the University of Chicago, completed a pediatrics residency at the University of California, San Diego, and a pediatric critical care fellowship at Children’s National Medical Center in Washington, D.C. Kochanek has been a faculty member at the University of Pittsburgh since 1986 and director of the Safar Center for Resuscitation Research since 1994. His major research interest is in mechanisms of secondary damage after severe TBI. He is principal investigator of a $10.4 million multicenter preclinical drug screening consortium funded by the U.S. Army to identify new TBI therapies.

Pitt Med: Where the Deans Were In Praise of Diversity hare the love — and the expertise. In recent years, at least eight former School of Medicine faculty members have gone on to become deans at other schools across the country. Of late, such deanships are held by former chair of Pitt pedi- n a burgeoning annual tradition begun in 2015, Satrics David Perlmutter, MD, who now oversees the medical school and a diverse community of faculty, physicians, all health sciences at Washington University in St. Louis, Steven Kanter, students, and trainees from the medical school MD, former SOM vice dean, who’s running the show at the University gathered together with spouses and partners of Missouri-Kansas City med school, and John J. Reilly Jr., MD, former to socialize, to celebrate their accomplish- top doc in the Department of Medicine, now leading the med school Iments, and to envision ways this community and health affairs at the University of Colorado. might grow more diverse, vibrant, and powerful. Held each fall at the Senator John Heinz History Center, the most recent iteration of the Toast to Diversity and Call to Action attracted more than 200 attendees, especially those who self-identify

14 Coming together to celebrate a campus-wide commitment to diversity

as members of groups underr­ epresented in the special events like an evening reception at the medical profession. Carnegie Museum of Art exploring the exhibit It was just one of many recent University She Who Tells a Story: Women ­Photographers events celebrating diversity, as the 2016–17 from Iran and the Arab World, the work of academic year was officially declared the 12 photographers who are challenging repre­ Year of Diversity at Pitt by Provost ­Patricia sen ­tations and perceptions of Middle Eastern Beeson. The campus-wide focus gives a signif- identity. Dozens of attendees, including med icant boost to the many ongoing diversity students, enjoyed a presentation and discussion programs supported by the Office of Health with one of the featured artists. Sciences Diversity. In addition to academic talks and informal mentoring, these include

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 15 NEWS & ACHIEVEMENTS PARTNERSHIPS AND NCI HONORS

“These projects are now being fleshed out to define a three-year plan Pitt, Pharma Take On Rare Diseases in New Partnership to codevelop a new molecule and lead compound that demonstrates effectiveness in an animal model of disease,” said Dietrich Stephan, PhD, who is leading the collaboration for Pitt, and is professor and chair of the Department of Human Genetics at Pitt’s Graduate School of Public he University of Pittsburgh has begun a research collaboration Health. “In addition to our teams, we have access to all of Shire’s capa- with global biopharmaceutical company Shire plc (LSE: SHP, bilities and contract research organizations, which includes custom NASDAQ: SHPG) to advance potential treatments for rare chemistry on the molecules and preclinical work.” diseases, where sizable unmet need exists. According to patient advocacy organization Global Genes, rare TThe collaboration combines the expertise of Pitt’s top-ranked health diseases affect more than320 million people worldwide — 10 times the sciences schools, led by the School of Medicine, with Shire’s research, number affected by all cancers combined and approximately the same development, and commercialization experience. number who suffer from the global epidemic of diabetes.­ Scientists have “We’re very excited to enter into a partnership with Shire Pharma- identified thousands of rare diseases, often having origins in genetic ceuticals,” said Pitt Chancellor Patrick D. Gallagher. “For decades, Pitt mutations that can pass through generations. These diseases are usually has been a leading research university; and, as we move into our next extremely severe, cause significant suffering, and very often result in phase, finding external partnerships with companies like Shire is criti- early death. While each individual disease generally affects fewer than cal for our future and a priority for Pitt.” several hundred thousand people, they collectively account for a massive Pitt has an extensive legacy of delivering groundbreaking health global burden of underserved patients. ­solutions, such as creating the first safe, effective polio vaccine, pioneering organ transplantation, and developing imaging technology to identify the protein plaques characteristic of Alzheimer’s disease in the living brain. “This collaboration has enormous potential to take what our scientists have already learned and will discover about rare illnesses and apply PSC Welcomes New Supercomputer this new knowledge to improve the care of patients who have other- wise garnered little attention,” said Arthur S. Levine, MD, Pitt’s senior ‘BRIDGES’ AIDS BIG DATA STUDIES vice chancellor for the health sciences and Petersen Dean of Medicine. “We want to make a difference for these families.” uring 2016, the Pittsburgh Supercomputing Center (PSC) has This kind of partnership is relatively new for Pitt but is the type of been celebrating its 30th anniversary with expanded capabil- relationship the University has identified as a strategic priority. Under the ities and recognition from the high-performance computing agreement, Pitt and Shire have selected an initial three projects that will (HPC) world. A joint effort of the University of Pittsburgh be funded by Shire and could ultimately result in a licensing agreement. Dand Carnegie Mellon University, PSC began with a machine that could • Solomon Ofori-Acquah, PhD, associate professor of medicine, will perform up to 840 million arithmetic operations every second. Shortly be investigating a molecular pathway that may lead to drug targets thereafter, new acquisitions started getting Burgh-flavored nicknames against sickle cell anemia. like “Mario” and “Warhol.” The latest, “Bridges,” was developed with a $9.65 million grant from •  David Whitcomb, MD, PhD, Giant Eagle Foundation Professor of the National Science Foundation to support investigators working in a Cancer Genetics and professor of medicine and of cell biology, will wide range of fields, including genomics, physical sciences, engineer- be researching a molecular pathway relevant to pancreatitis. ing, neuroscience, and the social sciences. •  Peter Wipf, PhD, Distinguished University Professor of Chemistry, “First and foremost, Bridges is about enabling researchers who’ve Dietrich School of Arts and Sciences, and Stephen Meriney, PhD, outgrown their own computers and campus computing clusters to professor of neuroscience, Dietrich School, will be studying a newly graduate to supercomputing with a minimum of additional effort,” says identified molecule that may lead to drug targets against the auto- Ralph Roskies, PhD, PSC scientific director and professor of physics, immune disorder Lambert-Eaton myasthenic syndrome. University of Pittsburgh. Bridges and PSC’s other upgrades have not gone unnoticed. HPCwire, a leading trade publication, cited PSC’s work for “Best Use of HPC Applications in Life Sciences” and “Best Use of High Performance Data Analytics,” with a particular shout-out to the Pittsburgh Genome “ T his collaboration has Resource Repository (PGRR). enormous potential to take PGRR is a resource for storing, accessing, and analyzing large, ­de-identified national sets of data like The Cancer Genome Atlas (TCGA) what our scientists have already from the National Institutes of Health, which are important for personal- ized medicine. PGRR is funded by Pitt’s Institute for Precision ­Medicine learned and will discover about (IPM) and University of Pittsburgh Cancer Institute (UPCI) and includes collaboration of faculty and staff fromIPM , UPCI, the Department of rare illnesses and apply this new Biomedical Informatics, the University of Pittsburgh Center for Simula­ tion and Modeling, PSC, and UPMC. knowledge to improve the care PGRR facilitates the large-scale profiling of TCGA’s 1.1 petabytes of of patients who have otherwise data, consisting of data on tumor samples from 11,000 cancer patients, to better understand genetic pathways and eventually enable person- garnered little attention.” alized cancer treatments.

16 NCI Recognizes Pitt Cancer Researchers

ake way for the Outstanding Investigator Award, a National Institutes of Health funding mechanism that rewards preeminent researchers with significant fund- ing for seven years. The award, also known as an R35 grant, is intended to provide stable support for more adventurous research ideas. Although the awards are fairly new (the first class of recipients was announced in summer 2015), faculty associated with the Olivera Finn MUniversity of Pittsburgh Cancer Institute (UPCI) are already well repre- sented among National Cancer Institute (NCI) honorees — acknowledg- ment that their work has unusual potential to advance cancer research.

Olivera J. Finn, PhD, Distinguished Professor of Immunology, and director of UPCI’s Immunology Program, has received $6.3 million to continue her investigations into identifying specific mechanisms of human antitumor immunity and developing prophylactic cancer vaccines. In particular, her group has identified a novel immune response to a tumor-­associated antigen, MUC1, expressed on breast, pancreatic, colon, ovarian, and other carcinomas of epithelial cell origin. MUC1-based vaccines were tested in several clinical trials in patients with these cancers. Finn also received the American Association of Immunologists’ highest honor in 2016, the AAI Lifetime Achievement Award.

Thomas W. Kensler, PhD, professor of pharmacology and ­chemical ­biology and coleader of the Cancer Epidemiology and Prevention Program at UPCI, has been awarded $6.3 million to support his studies on dietary chemoprevention — foods that may be used to reduce the risk of devel- oping cancer caused by unavoidable environmental toxins. Studies done by Kensler’s team in China have examined the bioactive molecules in broccoli and how they may help people there detoxify air pollutants. Thomas Kensler Broccoli and other cruciferous vegetables contain a naturally occur- ring molecular compound, sulforaphane, which activates protective protein pathways in cells that dampen risk from exposure to carcinogens.

Patrick S. Moore, MD, MPH, Pittsburgh Foundation Professor of ­Innovative Cancer Research and Distinguished Professor of Micro­ biology and Molecular Genetics, has received $6.4 million to continue exploring links between viruses and cancer. Together with his research partner and wife, Yuan Chang, MD, Moore has identified two differ- ent viruses that cause Kaposi sarcoma and Merkel cell carcinoma. The award will fund investigations that help to elucidate the mechanisms by which these viruses lead to the development of cancer and identify new ways to find cancer-causing viruses. Recently, the Moore-Chang lab found a new mechanism that cancer viruses use to regulate how cells translate RNA into proteins and developed an assay to discover a class of viruses called polyomaviruses.

Patrick Moore

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 17

Our mission is to educate science-based, skilled, and compassionate clinicians, as well as scientists whose biomedical research will better the human condition and advance our funda­ mental understanding­ of medical science. EDUCATION & TRAINING

Twin Pillars

t the University of Pittsburgh School of who then refers him to a radiologist for imaging and then Medicine’s annual curriculum colloquium in sends the result back to the patient and the primary doctor. 2012, med school dean Arthur S. Levine, MD, Ultimately, as students grow in their medical knowledge, LAP proposed a new program to neatly comple- grows with them. ment the school’s basic science strengths. He By the end of that first year, Bruno was expected to under- suggested pairing students with a moderately stand the biology of his patient’s conditions. As a capstone, he complex case, a patient whom they would and the other students each gave a presentation to the small follow through the course of their education. The only other group on the medical science behind their patients’ health longitudinalA experience, after all, is the Scholarly Project — concerns and wrote reflective papers on their experience with the four-year research endeavor Pitt med students undertake. the patient and LAP. This was like adding another, very different pillar to support The learning that goes on in these group sessions, though the curriculum. difficult to quantify, is a huge part ofLAP ’s success, the students Robin Maier, MD, MA, assistant professor of family medicine say. The sheer breadth of conditions and individual circum- and director of medical student education in that department, stances each student encounters — and therefore shares with the attended that colloquium and thought the program sounded others in his group — range from children with Down syndrome interesting. What impressed her, she says, is that “there’s this to adults with cancer, from people on dialysis to those newly sense of seeing the medical system from the inside out, from the diagnosed as diabetic. When, as has happened twice, a patient patient perspective,” rather than the usual doctor-side perspec- in the program dies, the students grieve together. When another tive. After telling the dean as much, she was quickly asked to patient’s diabetes comes under control — because of a dental head the pilot program. procedure, of all things — they celebrate. Maier launched the Longitudinal Alliance Project (LAP) So far, only a half-dozen or so of the nearly 100 patients in 2013. Med student Mike Bruno, who was in the inaugural enlisted have left the program. The most recent LAP group class of 10, says that the program “flips our roles and lets us numbers nearly 60, and next year’s group is expected to be sit beside the patient. And it has a whole different tone to it. even bigger. “It’s giving students real insight into how it is to Because after the visit, we don’t just go and talk to the doctor deal with the medical system … which is something that makes and debrief with the doctor: So what do you think of this every kind of physician a more effective physician,” says Maier. lab value? Instead, we’re debriefing with the patient: So what At its best, the program helps med students learn what kind of do you think about what the doctor said? Did you get everything doctors they want to be. out of that? That is really what distinguishes this experience — and why I think it’s valuable.” Each year of LAP is loosely guided by a theme. Getting to know the patient is the bulk of year one. Getting to know the How do we produce doctors health care team and its interprofessional interactions makes who are both science based up year two. Maier arranges for other health professionals to join small-group discussions that year, starting the tilt toward and compassionate? medicine-as-team-sport thinking. In the third year, the focus is on the different specialties of medicine and how they interact — how a family doctor might refer her patient to a cardiologist,

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 19 EDUCATION & TRAINING FUTURE PHYSICIAN-SCIENTISTS

Bolstering Clinical Research Careers Preparing Medical Students for 21st-Century Medicine

he best physicians have a solid grounding in the scientific method. They don’t have to be scientists, but they understand how research works and how the latest scien- tific discoveries can lead to better health for their patients. At Pitt, we challenge medical students to contribute to ­scholarly research during their med school years. In each graduating Tclass, without fail, there are med students who seize this opportunity and produce extraordinary results. Pitt’s inno- Q&A with Wishwa Kapoor, MD, MPH vative Scholarly Project requirement was introduced more than a decade ago. At the time, some said it would drive away applicants (who didn’t want to do research, presum- Physician-scientists — docs who work in the clinic and also pursue research — are invaluable in translating insights from the bench to patient ably), but the opposite has proven true. Today, admission is care. Yet, physicians with this double expertise are an ­endangered more competitive than ever. Pitt graduates are increasingly species, says Wishwa Kapoor, MD, MPH, Distinguished Service Profes- sought after by top residency programs, partly because of their sor and Falk Professor of Medicine, chief of the Division of General research experience. Even more telling, some of the nation’s Internal Medicine, and director of Pitt’s Institute for Clinical Research other elite medical schools now emulate Pitt’s ­Scholarly ­Education. According to a comprehensive assessment by the National Project. A few key features developed over the years have Institutes of Health last year, the average age of physician-­scientists is rising, and pressures in today’s funding climate create additional chal- greatly enhanced the success of the program, according to lenges for young trainees. Kapoor notes that many programs at Pitt are Donald B. DeFranco, PhD, associate dean for medical student attempting to address the shortage — from summer institutes for kids research and professor and vice chair of pharmacology and to seminars on work-life balance for junior faculty. chemical biology. “What is unique to Pitt, I think, is the direct What are some of the factors contributing to the leaky pipeline? connection to preparatory coursework. Methods and Logic in Medicine is a small-group, mentor-led class that prepares Becoming a physician-scientist requires more training, and you often them to do research, and it happens in the fall and winter of start out with more debt; research salaries are also lower than clinical salaries at the start. Also, in my view, these careers are a lot harder their first year.” Following that course, every med student than being a physician in practice. Not that being a physician is easy, is invited to take part in summer research between the first but the path is relatively straightforward: You join a practice and, gener- and second years of med school. “We are close to an all-time ally, patients keep coming. As a physician-scientist, though, you have high,” DeFranco notes, “with about 85 percent of the class to take the reins and guide your career in a creative way — ask the right doing summer research.” For the S­ cholarly Project, students ­questions, develop your research program, get the grants. There’s a signif- are paired with established scientists, including some of Pitt’s icant degree of burnout because of the stress of trying to get funding. most accomplished faculty members. Program organizers How can institutions help trainees succeed? have created a culture in which there is a clear focus on We need to make this track more accessible to younger researchers and providing guidance and tools for mentors. The mentor-stu- to train and retain more women and minorities. There is no magic-­bullet dent relationship is structured and supported from beginning solution. The focus must be not just on recruitment but on ­sustaining and to end. Depending on their interests, med students delve into supporting these investigators. But I think the most important compo- everything from wet-bench laboratory research to compu- nent of success is mentorship. Young investigators need mentors who tational biology. Some formulate clinical research projects can devote time to them and who are committed to promoting their careers — both at the home institution and with outside colleagues. with clinician mentors; others explore the subtleties of the doctor-patient relationship or mine public health data for How has Pitt been a leader in efforts to recruit, train, new insights into disease trends. In these and scores of other and sustain the careers of physician-scientists? ways, med students build their own scientific knowledge The School of Medicine has developed programs for medical students and develop skills that will help them to become clinicians to do substantive research. These programs (described on pages 20–24 who can make difficult diagnoses and help patients make of this report) help spark interest and are the beginning of research decisions based on evidence. careers.

20 SCHOLARLY PROJECT BY THE NUMBERS CLASS OF 2016 Addiction Medicine and the Opiate Abuse Epidemic 121 257 medical students presentations at national and international meetings ealth professionals from all disci- 106 of whom participated in summer research plines are joining forces to address programs between their first and second years of med school back in 2013 substance abuse, with a particular focus on opiate abuse. Pitt medi- 45 cal students begin learning about national or state awards Hthese conditions early in the first year and 145 continue the process throughout the curric- peer-reviewed publications ulum during sessions that provide essential plus an additional 41 submitted and/or under review knowledge and patient-counseling skills 56 in pain management and addiction. New local awards Web-based instructional modules are being introduced to provide students with added exposure to patient cases in these areas. In spring 2015, Pitt’s Schools of the Health Sciences introduced a unique 2016 O’MALLEY AWARD WINNERS presentation that was delivered to every At Scholars Day 2016, four graduating MD students were individually honored for their Scholarly student graduating this year from Pitt’s Project efforts with a Bert and Sally O’Malley Award for Outstanding Medical Student Research. Schools of Medicine, Dental Medicine, Pharmacy, Nursing, Health and Rehabil- The best of the best from the Class of 2016: itation Sciences, and Public Health. The program, “A Man-Made Epidemic: Uses and Abuses of Opioids,” is the brainchild of med school dean Arthur S. Levine, MD, who is also senior vice chancellor for the health sciences, to convey the urgency and importance of the latest information on opioid addiction to students as they embark on their careers as health professionals. In addition, the med school joined more than 60 American medical schools in an BRIAN AHN, MD BHAVANA OLUBUSOLA ERIC ETCHILL, MD Association of American Medical Colleges– HDC Expression CHAPMAN, MD OLUWOLE, MD, MS Massive Transfusion organized pledge to, beginning in fall 2016, and Histamine in MicroRNA-363 Targets Practices in the Arterial Stiffness and require all medical students to undergo the Development of Myosin 1B To Reduce Non-Trauma Setting Cognitive Functioning Malignant Glioma Cellular Migration in in Individuals with prescriber education in line with the newly Head and Neck Cancer Residency Match: Sickle Cell Disease released Centers for Disease Control and Residency Match: General Surgery, Prevention Guidelines for Prescribing Residency Match: Residency Match: Internal Medicine, Johns Hopkins Opioids for Chronic Pain. UPMC Medical Education Preliminary Internal Hospital/Johns Internal Medicine/ Program/University Medicine, University Hopkins University, Global Health, UPMC of Pittsburgh of Texas MD Anderson Baltimore, Md. Medical Education Cancer Center, Program/University Mentor: Houston, Texas Mentor: of Pittsburgh Hideho Okada, MD, PhD Matthew Neal, MD Radiation Oncology, Professor of Neurological Assistant Professor Mentor: Baylor College of Surgery, University of of Surgery and of Enrico Novelli, MD, MS Medicine, Houston, Texas California, San Francisco Critical Care Medicine Assistant Professor of Medicine, Division of Mentors: Hematology/Oncology, Jennifer Grandis, MD and of Clinical and American Cancer Society Translational Science Professor, Associate Vice Chancellor for Clinical and Translational Research, and Professor of Otolaryngology, University of California, San Francisco

Saleem Khan, PhD Professor of Microbiology and Molecular Genetics

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 21 EDUCATION & TRAINING 5-YEAR MD PROGRAMS

In-Depth Study CSTP GRADUATES AND THEIR RESIDENCY PROGRAMS: for Med Students JULIE BOIKO, MD, MS JEE-HONG KIM, MD Residency Match: Residency Match: Pediatrics, University of California, Otolaryngology, University of San Francisco Southern California, Los Angeles

hrough a raft of specialized programs, Mentor: Mentor: diverse research opportunities, and areas Paul Szabolcs, MD, Professor of Cuneyt M. Alper, MD, Professor of concentration, med students at Pitt are Pediatrics and of Clinical and of Otolaryngology and of Clinical Translational Science; Chief, Division and Translational Science able to explore their interests in depth. Many of Blood and Marrow Transplantation will take a year off at some point to earn a and Cellular Therapies OLUBUSOLA OLUWOLE, MD, MS master’s degree in public health, biomedical Residency Match: ethics, or a related field; others will devote PHILLIP CHOI, MD Internal Medicine/Global Health, Residency Match: Neurological UPMC Medical Education Program/ a full year to research through either the Clinical Scientist Surgery, University of Texas Health University of Pittsburgh Training Program (CSTP) or the Physician Scientist Training Science Center at Houston T Mentor: Program (PSTP). Mentor: Enrico Novelli, MD, MS, Assistant David O. Okonkwo, MD, PhD, Professor of Medicine, Division of Associate Professor of Hematology/Oncology, and of Neurological Surgery and of Clinical and Translational Science CSTP Clinical and Translational Science

XIAORAN ZHANG, MD, MS DOUGLAS HOLT, MD The Clinical Scientist Training Program offers a leg up for Residency Match: medical students who show an interest in and a talent for Residency Match: Neurological Surgery, UPMC Medical Preliminary Internal Medicine, ­clinical research. Select students whose mentored scholarly Education Program/University of University of Utah Affiliated Pittsburgh projects meet the NIH definition of clinical research are invited Hospitals, Salt Lake City Mentors: Radiation Oncology, University to delve deeper into their research during a fifth year of training. Nduka Amankulor, MD, Assistant of Colorado School of Medicine, Interested students apply to CSTP in January of the year they Professor of Neurological Aurora, Colo. plan to commit to full-time research (typically between the Surgery and of Clinical and Mentors: Translational Science third and fourth years of medical school). Selected students Dwight E. Heron MD, Professor Michael T. Lotze, MD, Professor are appointed as research fellows for the research year, during of Radiation Oncology, of of Surgery and Vice Chair for Research, which they receive a living stipend, research funds, travel funds, Otolaryngology, and of Clinical Department of Surgery; Professor and Translational Science health insurance, and tuition toward the graduate certificate of Immunology and of Clinical and David A. Clump II, MD, PhD, Translational Science; Professor of in clinical research. Assistant Professor of Radiation Bioengineering, Swanson School After successful completion of the fellowship year, they receive Oncology and of Clinical and of Engineering a CSTP scholarship toward the final year of medical school. By Translational Science providing formal research training and partial tuition assistance, ALEXANDER KHALAF, MD CSTP seeks to increase the number of Pitt grad­uates who choose Residency Match: clinical research careers and contribute to the vital work of trans- Transitional Medicine, UPMC Medical lating biomedical science into clinical care. After leading the Education Program/University of program for 12 years, Amber E. Barnato, MD, MPH, MS, associate Pittsburgh Radiology-Diagnostic, Stanford University, Stanford, Calif. professor of medicine and of clinical and translational science, Mentor: stepped down as CSTP director in 2015. Margaret B. Conroy, MD, Howard Aizenstein, MD, PhD, MPH, associate professor of medicine, School of Medicine, and Professor of Psychiatry and of of epidemiology, Graduate School of Public Health, will lead the Clinical and Translational Science; Associate Professor of Bioengineering, program going forward. Conroy, who is also assistant dean for Swanson School of Engineering medical student research, plans to formalize a CSTP peer mento- ring program and further strengthen the continuity between the Scholarly Project and the research that CSTP students conduct during the research year. Several members of the Class of 2016 are products of Pitt’s CSTP, having previously completed the research year.

22 PSTP HHMI selected 66 top medical and veterinary students from 34 schools in the nation to conduct full-time biomedical research in its The Physician Scientist Training Program (PSTP) is a five-year Medical Research Fellows Program. The $3 million annual initiative is designed to develop the next generation of physician-scientists by giving program for exceptionally talented students who, in addition to the students a full year of mentored research training with some of the the regular curriculum, undertake two summers and a dedicated nation’s top biomedical scientists. The fellows put their medical school year of laboratory-based research training, as well as enrichment coursework on hold and spend a year immersed in basic, translational, courses, to prepare for careers in academic medicine. Those or applied biomedical research. selected for the program receive partial tuition assistance for “The HHMI Med Fellows Program is one of the few in the nation that enables MD and DVM students to engage in very high-quality research the four years of medical school plus a stipend during the two for an entire year,” said David J. Asai, senior director in science education research summers and the research year. The Class of 2016 at HHMI. “This engagement is perhaps the best way for talented students included three graduating PSTP students who matched to top at this stage in their training to understand the powerful opportunity residency programs in some of the most competitive medical that emerges at the intersection of medicine and laboratory research. specialties. Three members of the Class of 2016 are products We hope that each of the med fellows seriously considers pursuing a career as a physician-scientist.” of Pitt’s PSTP, having previously completed the research year. The fellowships permit the students to take a break from their ­medical school courses and spend the year conducting basic, translational, or PSTP GRADUATES AND THEIR RESIDENCY PROGRAMS: applied biomedical research at academic or nonprofit research institu­ tions anywhere in the United States. For 2016, 195 students from around the country applied to the program. MICHAEL BURROW, MD BHAVANA CHAPMAN, MD Each student applied with a mentor and submitted a research proposal. Residency Match: Residency Match: Each medical fellow receives $41,000 in grant support, and fellows are Ophthalmology, University of Utah, Preliminary Internal Medicine, Salt Lake City University of Texas MD Anderson eligible to apply for a second year in the program. (One Pitt awardee, Cancer Center, Houston Tolani Olonisakin, is among the 13 HHMI fellows from 2015 who will be Mentor: supported for an additional year.) James Funderburgh, PhD, Radiation Oncology, Baylor College Professor of Ophthalmology of Medicine, Houston THE AWARD-WINNING STUDENTS AND THEIR PROJECTS: and of Cell Biology Mentors: Jennifer Grandis, MD, American ERIN CUMMINGS, MD Cancer Society Professor, Associate POOJA KARUKONDA MONDIRA RAY Residency Match: Vice Chancellor for Clinical and Investigating the Role of Radiation Construction and Validation of Pediatrics, UPMC Medical Education Translational Research, and Professor Therapy in Promoting an Anti-Tumor Pathway-Oriented Features for Use in Program/University of Pittsburgh of Otolaryngology, University of California, San Francisco Response in the Host Machine Learning Programs To Predict Mentor: Breast and Lung Cancer Outcomes Saleem Khan, PhD, Professor Mentor: Gary Silverman, MD, PhD, Harriet B. of Microbiology and Molecular Christopher Bakkenist, PhD, Associate Mentors: Spoehrer Professor and Chair of Genetics Professor of Radiation Oncology Rebecca S. Jacobson, MD, MS, Pediatrics, Washington University Professor of Biomedical in St. Louis School of Medicine THIAGU MEYYAPPAN Informatics and of Clinical and Translational Science In Vivo Induction of Antigen Specific Tregs To Prevent the Ziv Bar-Joseph, PhD, Professor Onset of Type 1 Diabetes of Computational Biology, Carnegie Mellon University Mentor: Steven R. Little, PhD, William PSTP Students Win Prestigious Kepler Whiteford Professor and CYRUS TSANG Chair, Department of Chemical and The Role of Synaptic Zinc in HHMI Fellowships for 2016–17 Petroleum Engineering, Swanson Tinnitus-Related Hyperactivity School of Engineering Mentor: Thanos Tzounopoulos, PhD, ll three PSTP students graduating with the Class of 2016 shared TOLANI OLONISAKIN Professor of Auditory Physiology something in common: Each was awarded a highly coveted Investigating the Role of and Associate Professor of Platelet-Derived Thrombospondin-1 Otolaryngology research training fellowship through the Howard Hughes in Limiting Neutrophil Killing of Medical Institute (HHMI) Medical Research Fellows Program. Klebsiella pneumoniae Carrying on this distinguished tradition, five currentPSTP Astudents were also named HHMI fellows in 2016. The students will be Mentor: Janet S. Lee, MD, Associate Professor supported through a one-year leave of absence, during which they’ll of Medicine, Division of Pulmonary, dedicate themselves to their research projects and associated research Allergy, and Critical Care Medicine training. Pitt’s success in this prestigious arena stems in part from the specialized grant writing course offered toPSTP students between the first and second years of med school. In addition to learning widely applicable keys to successful grant writing, the course provides very specific feedback on each student’sHHMI proposal.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 23 EDUCATION & TRAINING MATCH DAY, PHD PROGRAMS

On average over the past six years, MSTP students have ­coauthored six scientific publications (three as first author) by the time they graduate. Other MSTP bragging points include Pitt’s enviable success rate in winning F30 awards from the It’s an MSTP Match National Institutes of Health. Also known as Ruth L. Kirschstein National Research Service Awards, F30s are granted to MSTP students who demonstrate the potential to become highly atch Day is a big deal for all graduating trained, productive, and independent physician-scientists. NIH’s med students, but for those in the Medical ultimate goal with this program is to increase the number of Scientist Training Program (MSTP), future investigators with both clinical knowledge and skills in Pitt’s combined MD/PhD program, the basic, translational, or clinical research. In recent years, roughly anticipation has been building for an half of Pitt’s MSTP students have earned NIH grants. especially long time. Most classmates F30 AWARDS TO CURRENT MSTP STUDENTS: with whom they entered med school are long gone, because MSTP students begin with two years of MD training then break for a few years of PhD research before COLIN BECKWITT ANNIE LIU M Oxygen’s Impact on Tumor Organization and Plasticity of returning to complete the MD. While in the midst of their PhD Metastasis Dormancy and Therapy Post-Synaptic Targets of Individual research, they watch most of the MD students they entered National Cancer Institute Glomeruli in the Mammalian with celebrate graduation and move on to residency positions. Olfactory Bulb Mentor: Match Day for MSTP students typically arrives about seven National Institute on Deafness and Alan H. Wells, MD, DMS, Thomas J. Other Communication Disorders years after they begin medical school. In 2016, Pitt said fare- Gill III Professor of Clinical Pathology well to four of these budding physician-scientists. “In 2016, and Executive Vice Chair for Clinical Mentor: our graduating students matched into top-tier programs,” said Pathology, Department of Pathology; Nathan Urban, PhD, Professor Professor of Computational and and Vice Chair of Neurobiology Richard Steinman, MD, PhD, associate dean for MSTP and asso- Systems Biology; Professor of ciate professor of medicine and of pharmacology and chemical Bioengineering, Swanson School J. RANDALL McAULEY biology. “More notably, the academic programs that they chose of Bioengineering The Carma3/Bcl10/Malt1 for residency training have a tradition of supporting physi- Signalosome in Osteosarcoma SOMA JOBBAGY Metastasis cian-researchers. Across the board, our graduates will continue Protective Effects of Nitro-Oleic National Cancer Institute both their clinical and scientific training with guidance from Acid in Hypertensive Chronic Kidney Injury Mentor: outstanding role models at their new institutions.” Peter Lucas, MD, PhD, Associate National Institute of Diabetes and Professor of Pathology and of Digestive and Kidney Diseases PITT’S 2016 MSTP GRADUATES AND THEIR RESIDENCY MATCHES: Pediatrics Mentor:

Bruce Freeman, PhD, UPMC Irwin ERIC ZIMMERMAN KAREN CHIU, MD, PHD NIYATHI HEGDE SHAH, MD, PHD Fridovich Professor and Chair of Nucleus Reuniens Regulation of Pharmacology and Chemical Biology Residency Match: Residency Match: Ventral Tegmental Area Dopamine Internal Medicine, Weill Cornell Internal Medicine, UPMC Medical Neuron Activity: Relevance to Medical College, New York, NY Education Program/University JOHANNES KUTTEN Psychosis of Pittsburgh Tsp1-Cd47 Signaling Limits National Institute of Mental Health Mentor: Restoration of Decellularized and Michael J. Palladino, PhD, Associate Mentor: Synthetic Tracheal Transplants Mentor: Professor of Pharmacology and Elias Aizenman, PhD, Anthony A. Grace, PhD, National Institute of Biomedical Chemical Biology Professor of Neurobiology Distinguished Professor of Imaging and Bioengineering Neuroscience and Professor ANDREY FINEGERSH, MD, PHD JEFFREY WALCH, MD, PHD Mentor: of Psychology, Dietrich School Jeffrey S. Isenberg,MD , MPH, of Arts and Sciences Residency Match: Residency Match: Associate Professor of Medicine; Otolaryngology, University of Preliminary Surgery, University Associate Professor of Bioengineering, California, San Diego of Maryland, Baltimore Swanson School of Engineering Mentor: Mentor: Gregg Homanics, PhD, Professor of Fadi Lakkis, MD, Frank and Athena Anesthesiology and of Pharmacology Sarris Professor of Transplantation Pitt’s MSTP has 80 students currently — big enough to maintain and Chemical Biology Biology, Department of Surgery; a lively and diverse group dynamic. In the 2016–17 academic Professor of Immunology and year, MSTP boasts its highest level of NIH support since its of Medicine founding 30 years ago, with 20 Pitt MD/PhD students funded by NIH per year. As usual, students in the program welcomed an influx of fresh faces at the start of the academic year. The research interests of the incoming class reflect a few of the many research strengths

24 of the University, ranging from molecular Class of 2016 Remakes pharmacology to epidemiology, with indi- vidual students focusing on immunology, Match Day Experience clinical and translational science, neuro- science, structural biology, and molecular biophysics. n Match Day 2016, Pitt med’s senior class scored a record number of residency placements in 30 states and the nation’s capital, with 38 “The 14 new students who make up ­graduating students continuing their medical training right here in the this year’s incoming class stood out for City of Champions. Match Day is a familiar annual ritual, but while the their research accomplishments and residency assignments of the 141 individuals in the Class of 2016 were their smart plans for how they would still sealed up in neat stacks of envelopes, the grand spectacle of Match use our program to further develop Day 2016 was — dare we say it — divergent. their already outstanding skills,” said Seniors elected to forgo the lively, one-by-one chaos of “hear the dean call your Oname, get an envelope,” in favor of a mass opening of match letters. The tearing of Steinman. “They were drawn to Pitts- envelopes was quickly followed by group rejoicing and opportunities for students burgh by specific faculty members and to grab a microphone and share their results from the stage. research programs that buoy our national “I liked the format change, because there was less pressure for students to open reputation in biomedical science.” their envelopes in front of everyone,” said Jacqueline Birkness, now a pathology intern at Johns Hopkins Hospital. “I matched into my top choice!” she said. “I was happy to have my parents and closest friends there to share the moment of me opening my envelope,” said Debra Okafor, former president of the Student National Medical Association at Pitt. “My friends and I did a countdown together. Medical School I was overjoyed and cried as soon as I saw my results.” Okafor is now a pediatrics resident at Yale-New Haven Hospital. While at Pitt, Isn’t Just for MDs she assisted in neonatology and gastroenterology research studies at Magee-­ Womens Hospital of UPMC and Children’s Hospital of Pittsburgh of UPMC. “You should be applauded and celebrated,” said Joan Harvey, MD, associate dean for student affairs. “You should know how proud of each and every one of n addition to the approximately 600 students you we are.” in the four-year MD program, there are Malcolm Dombrowski was quick to return Harvey’s praise, saying he “couldn’t nearly 300 students pursuing PhD degrees be happier” with his med-school experience. He described the med school as in 12 programs that include neuroscience, bio­ a “strong collegial and academic environment” with a diverse student body that medical informatics, computational ­biology, shares common goals. In fact, he holds the Pitt environment in such high esteem Imolecular biophysics and structural biology, that it was his first choice for residency. He was pleased to open his envelope and and clinical and translational science. The find that he’ll remain here for the next six years as an orthopaedic surgery resident. breadth and depth of research activity at the “Pitt’s clinical teaching is definitely among the top in the nation,” Dombrowski University are extensive enough that graduate added. “And based on the reactions and immediate respect I was given when students in a wide range of disciplines receive interviewing, you could tell that faculty across the country know what type of training that allows them to conduct research training happens at Pitt.” at the cutting edge of biomedical science. In addition to those in Pitt’s residency programs, large cohorts of 2016 Pitt med Of note in 2016, Tianyu (Emma) He, a fifth- graduates are also training at Harvard, Johns Hopkins, and Case Western Reserve year PhD student in the Cellular and M­ olecular Universities, among many others. Pathology program, was awarded a Young Investigator Prize at the 21st International AIDS Conference in Durban, South Africa, for her abstract presentation of a new strategy for reac- tivating HIV from reservoirs. The $2,000 prize is a means of supporting young researchers who demonstrate innovation, originality, ratio- nale, and quality in HIV research. Her thesis advisor is Ivona Pandrea, MD, PhD, professor of pathology, School of Medicine, and of infec- tious diseases and microbiology, Graduate School of Public Health.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 25

ANDY SAYS, “WELCOME PITT MED!”

A new med-school rite of passage was introduced in August 2015, and now two entering classes have enjoyed a fun and funky evening to celebrate their first week of med school.

THE PLACE: The Andy Warhol Museum on Pittsburgh’s North Side

THE VIBE: From Warhol Hipster/Chic to Business Casual

THE SCENE: Music, silk-screening, scavenger hunt, and more, all kicked off by the sorting of students into “houses,” which are led by their advisory deans.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 27 EDUCATION & TRAINING CLASS OF 2020 WARHOL WELCOME

28 UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 29 EDUCATION & TRAINING BOUNDLESS HORIZONS

Med Student Turns Entrepreneur

n any given year, a number of Pitt medical students will take a temporary leave of absence to pursue opportunities related to their medical education. In addition to the formal med-school programs like the MSTP, PSTP, and CSTP, students might accept a year-long research opportunity at another institution or complete a master’s Idegree in a health-related field. Matt Kesinger’s current leave of absence is a bit unusual. As a CSTP student entering his final year of med school, he had already taken some time to immerse himself in clinical research. Then, he found an idea so compelling that he felt he had to put med school on hold to launch a medical device company, Forest Devices. The fledgling company’s product is AlphaStroke, a portable device that uses electrodes placed on the forehead to quickly diagnose stroke, enabling first responders to save precious time and send stroke victims to the nearest hospital equipped to treat their condition. “We all go into medicine for different reasons, but one is universal, Med Student Named and that’s the potential positive impact we can have on others,” says Kesinger, who had long been drawn to the ways in which tinkerers Tillman Scholar and engineers developed medical devices to improve health care. He had even developed a new design for a chest tube and run some experiments using it. That experience was interesting, but the idea behind AlphaStroke was absolutely compelling, he says. “When econd-year med student Sangki Oak has been I realized I could take existing technology and refit it for stroke named a Tillman Scholar by the Pat Tillman ­identification, I saw that all the key pieces for successful commer- Foundation. This prestigious honor is reserved cialization were there, and I said, ‘I have to do this.’” for a small number of post-9/11 military Kesinger worked as a paramedic before med school, and he recalls veterans (or their spouses) who demonstrate being called to a home where a 60-year-old woman had suddenly become weak and confused. Kesinger and his colleagues followed strength in character, academic excellence, protocol. They took her to the nearest hospital to get a CT scan. and extraordinary potential in the fields of “She was diagnosed with a stroke. Unfortunately, this was not medicine, law, business, education, and the arts. Founded a hospital that could treat stroke, so she had to be transported by in 2004, the foundation honors the memory of Pat Tillman, helicopter to one that could,” he says. “That delay cost her two hours S who passed on a lucrative professional football contract to of brain. That’s the difference between being able to walk out of the hospital and go home or never walking again and living in a nursing enlist in the U.S. Army and was killed in action in 2004. home. That’s the difference between a single hospital bill and requir- Tillman Scholars receive academic scholarships and support ing expensive medical care every single day for the rest of her life.” for study-related expenses. Kesinger says this is not an uncommon story. Half of all stroke A veteran of the U.S. Navy, Oak served as senior medic for a patients — hundreds of thousands of people a year — go to the wrong team of Marines deployed to Afghanistan in 2009 and in 2010. hospital first. With AlphaStroke, first responders would diagnose In addition to providing medical care to their Marines, Oak stroke in the field and take patients straight to the hospital that can best treat them. Forest Devices began its first clinical trial in2016 , and his team worked on improving public health and health with the pivotal trial tentatively scheduled for early 2017. Kesinger infrastructure for the local population. In A­ fghanistan, Oak predicts that, if the pivotal trial demonstrates that AlphaStroke can developed a passion for helping those in medically under- both identify stroke and differentiate between the biggest, most seri- served communities worldwide. His position as a medic, as ous strokes and the smaller ones, FDA approval will result. well as the team member in charge of aid and development Kesinger’s ongoing entrepreneurial work is allowing him to complete a master’s degree in health care management at ­Carnegie efforts for the local population, familiarized him with the Mellon University — a two-year program for which he has a full needs and struggles of those in remote parts of the world scholarship. And med school? Don’t worry, he says, he’ll be back and those caught in the crossfire of armed conflict. for that final year. With any luck, he and AlphaStroke will be grad- Since leaving the military, Oak’s passion for medicine uating into the larger world of medicine around the same time. has been reinforced by visits with Syrian refugees in camps near the Iraq border and through providing medical care to those affected by the earthquake in Nepal. He credits the military with providing him the temperament and skills to operate in these harsh and remote places and the aptitude to develop solutions with limited resources.

30 Global Partnerships Alumnus Ryan McGarry Returns for Graduation Keynote Expanding and Maturing

he Class of 2016 — and all those in attendance for the awarding THE SCHOOL OF MEDICINE OPERATES ON A GLOBAL STAGE, WITH of diplomas — were treated to an engaging keynote address by Pitt med alumnus Ryan McGarry, MD, emergency medicine ACTIVE COLLABORATIONS CONNECTING PITTSBURGH WITH AFRICA, physician at NewYork-Presbyterian Hospital and a clinical ASIA, EUROPE, AND SOUTH AMERICA. OF PARTICULAR NOTE OVER instructor in emergency medicine at Weill Medical College THE PAST FIVE YEARS, PROGRAMS LINKING US WITH CHINA AND ofT Cornell University. KAZAKHSTAN HAVE MATURED INTO THRIVING PARTNERSHIPS. McGarry has had a lifelong interest in filmmaking, which he explored while a med student at Pitt. During his emergency medi- Through the School of Medicine’s partnership with Tsinghua ­University cine clerkship at Los Angeles County General Hospital, he began School of Medicine in Beijing, medical students at this most filming the daily events in the hospital’s emergency department. This prestigious of Chinese scientific institutions undergo a rigorous, two-year project eventually became the riveting and poignant documentary biomedical research training program in Pittsburgh. Initiated in 2012, filmCode Black, which received critical acclaim and was named Best the historic agreement was recently renewed for a second five-year Documentary at the 2013 Los Angeles Film Festival. term. As of August 2016, Pitt’s Tsinghua Scholars program has 67 alumni It captured the interest of CBS, too, and the television network and 25 active scholars on premiered the scripted series Code Black on its Wednesday-night campus, working in the lineup in September 2015, with McGarry as an executive producer. labs of some of Pitt’s most After a very successful first season, Code Black was renewed for a accomplished biomedical second season with CBS, beginning in fall 2016. researchers. While in Pittsburgh for the Class of 2016’s graduation ceremony, The 2016 edition of the McGarry took in the full Pittsburgh nostalgia experience, including a annual Pitt-Tsinghua Joint visit to Primanti’s for a sandwich with the works. He also d­ elivered a Symposium was held in special presentation, “Code Black and the Television Doctor ­Paradox: Beijing. Eight Pitt faculty Popular and Powerless in the 21st Century,” sponsored by Pitt’s Center members made the jour- for Research on Media, Technology, and Health. ney from Pittsburgh and took part in scientific presentations alongside their peers from Tsinghua University. Cutting-edge topics included Med Student is One of Forbes Top 30 under 30 cryo-electron microscopy and viral protein assembly, computational modeling, the use of advanced quantitative methods to improve bedside care, advances in precision medicine, Big Data and computational model- ing to counter epidemics, and advanced clinical decision analysis. The fter a baseball injury during high school, Christopher 2017 joint symposium will be held in Pittsburgh. Murawski showed such an interest in the treatment plan for his damaged ankle ligament that he was invited to shadow The School of Medicine initiated a collaboration with China’s renowned his orthopaedic surgeon on rounds — once his ankle was Central South University Xiangya School of Medicine in 2012, as healed. Murawski studied neuroscience as a Pitt undergrad, well. Under the five-year agreement, Pitt provides two years of rigor- Abut he never strayed far from his interest in orthopaedics. In fact, his ous biomedical research training to medical students, most of whom keen interest led to an invitation to work in the lab of Freddie Fu, MD, have already undergone six years of medical school, including clinical Distinguished Service Professor, David Silver Professor and chair of clerkships. As of September 2016, 24 of these medical students are on the Department of Orthopaedic Surgery. Murawski helped Fu’s team campus, and 10 have recently returned to Changsha to graduate from with sophisticated anatomical explorations of normal and damaged medical school after their two years in Pittsburgh. In 2014, spurred on anterior cruciate ligaments, and he evaluated the effectiveness of by the success of this global collaboration between universities, Xiangya different types of surgical reconstructions — all as an undergrad. Hospital formed a partnership with UPMC to establish an international Since beginning med school in 2014, he’s continued to work on medical center that will improve access to high-quality care for patients research projects through the Department of Orthopaedic Surgery. within the region. The third-year medical student’s research portfolio has grown to more than 55 peer-reviewed publications, and he’s participated in In 2012, the School of Medicine was selected to guide the Republic of more than 60 conference presentations. Kazakhstan’s Nazarbayev University (NU) as it establishes its own In January 2016, Murawski was named one of Forbes magazine’s medical school, which aims to educate physician-scientists to become Top 30 under 30 in health care. The magazine describes this group this Central Asian nation’s next leaders in health care, medical education, as “the brightest young entrepreneurs, breakout talents, and change and biomedical research. Pitt has partnered with NU to institute a U.S.- agents” worldwide. style curriculum; design and develop teaching facilities; recruit and train school leadership and faculty; plan organizational and administrative structures, policies, and procedures; and develop courses, syllabi, and clinical experiences with the participation of physician-educators from Kazakhstan and around the globe. In August 2015, the NU School of Medicine welcomed its first class of 20 students, followed by a second class of 32 students in August 2016.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 31

We aim to bring about transformational changes in American medicine by exploring the most fundamental and important areas in biological science and clinical care. RESEARCH

Linked Genes Provide Novel Insight on Disease PITT-DEVELOPED WEBSITE PROVES BOON TO EVOLUTIONARY BIOLOGY RESEARCHERS

NA travels its own peculiar path over time supported results that are easy to interpret, he says, adding that to ensure that we come out on the right side as of the 12 months ending in July 2016, more than 3,000 unique of the “adapt or die” equation. And at the users representing “all inhabited continents” had used the portal. genetic level, we share the dance floor with Clark’s lab recently used a modifiedERC method to correlate creatures great and small whose response to evolutionary patterns of genes with environmental influences evolutionary pressures can bring new clarity in marine mammals compared to their terrestrial compatriots. to the cellular functions, proteins, and other These analyses traced molecular-level contributions to morpho- regulatory molecules linked with human disease. logical and physiological adaptations necessary to support D Developed by Nathan Clark, PhD, assistant professor of species transition from landlubber to sea dweller. computational and systems biology, and colleagues, this bio-­ Published in the July 2016 issue of Molecular Biology and informatics approach—known as evolutionary rate covariation Evolution, the Clark team reported on accelerated changes in (ERC)—correlates branch-specific evolutionary rates of a chosen genes affecting muscle formation, lipid metabolism, sensory pair of genes. The fundamental concept behind ERC is that systems, skin, lung, and connective tissue — broadly recognized functionally related genes should respond similarly to evolutionary functional adaptations for which underlying mechanisms are pressures and, therefore, be easier to track and characterize. not well understood. By parsing such genetic “guilt by association” in Drosophila “We’re advancing this work now to look at subterranean and other species, Clark and colleagues have been able to iden- mammals and the changes going on in these animals that are tify new protein networks that influence reproduction PLOS( essentially blind,” Clark says of an ongoing collaboration with Genetics, 2014), amino acid transporters that affect signal trans- Kanwal Nischal, MD, professor of ophthalmology and chief of mission in the glutamatergic neuromuscular junction (Nature the Division of Pediatric Ophthalmology, Children’s Hospital of Scientific Reports, 2016), and key evolutionary signatures among Pittsburgh of UPMC. “We’re looking to see what new eye genes a variety of disease genes that could help to untangle previ- we might uncover.” ously unknown relationships between clinically distinct disease Visit the ERC website: csb.pitt.edu/erc_analysis/index.php. processes (PLOS Genetics, 2015). Over the past year, the Clark team has built a publicly acces- sible Internet portal to assist researchers at Pitt and elsewhere with ERC-based investigations. A kidney disease researcher “Imagine you’re a kidney disease researcher interested in a pathway that leads to sodium permeability on the cell surface. interested in sodium permeability Take a gene that you know influences that pathway, put it into the on the cell surface can select a gene portal, and it will serve you up genes that are highly correlated with your gene,” says Clark. “We’ve shown now through a known to influence that pathway, number of published studies that this works.” put it into the portal, and receive Portal structure is described in the August 2015 issue of the journal Bioinformatics. It contains data on three taxonomic a list of other, highly correlated genes, groups —33 mammal species, 12 Drosophila species, and 18 kinds including some surprises. of yeasts. Website analyses are designed to provide statistically

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 33 RESEARCH FUNDING AND SUPPORT

To Infinity and Beyond PITT RESEARCH STUDY TO LAUNCH INTO SPACE

ocky S. Tuan, PhD, Arthur J. Rooney Sr. Professor of Sports Medicine and Distin- guished Professor of Orthopaedic Surgery, has received a $500,000 grant from the Center for the Advancement of Science in Space (CASIS) to support experiments on a 3D micro­physiological system (MPS) that will be implemented on board the Inter ­national Space Station (ISS) to evaluate the accelerated aging and degeneration processes of bones that occurs under microgravity conditions during space travel. The award, announced at the White House Organ Summit in June 2016, is part of the 3D Microphysiological Systems for Organs-on-Chips Grand Challenge by CASIS, which Rwas chosen by the U.S. National Aeronautics and Space Administration (NASA) to manage the ISS U.S. National Laboratory in 2011. “Studying such rapid “Studying such rapid progression of the disease offers great advantages to developing progression of the treatments for osteoporosis faster and more effectively, in ways that are not possible on Earth,” said Tuan. “Our research will benefit not only the health of astronauts who may face disease offers great long stays in space on the ISS or a future journey to Mars but also will help people on Earth, providing capabilities for the screening of drug therapies, enhancing personalized medicine, advantages to devel- and developing bioreactor technologies for tissue engineering.” Tuan is internationally known for his research in stem cell biology, musculoskeletal tissue oping treatments for engineering, and regenerative medicine and for innovative leadership in biomedical education. He is also associate director of the joint Pitt/UPMC McGowan Institute for Regenerative osteoporosis faster Medicine, director of the Center for Military Medicine Research, and director of the Center and more effectively, for Cellular and Molecular Engineering. Under Tuan, Pitt’s Center for Cellular and Molecular Engineering focuses on the science of in ways that are not treating injuries and diseases of the musculoskeletal system, using stem cells and biomateri- als in combination with bioreactor and biofabrication technologies, including 3-dimensional possible on Earth.” printing, for functional skeletal tissue engineering and regeneration. The MPS project has also been partially funded by the Ri.MED Foundation, a collaborative effort of Italy’s government, the University of Pittsburgh, andUPMC . The foundation, based in Palermo, Italy, promotes, supports, and leads biomedical and biotechnological research projects, with an emphasis on the translation of innovative results into clinical practice.

34 diseases is relatively small, the severity of disease NEW METHODS TO TRACK and their potential emergence in larger popula- PLACENTAL HEALTH tions or for use as bioweapons drive the necessity for development of countermeasures,” he said. The trophoblast — the outermost layer of the Klimstra is principal investigator on two National placenta — regulates maternal-fetal gas exchange, Institutes of Health grants to research eastern nutrient delivery, waste removal, immunological­­ Grants equine encephalitis virus (EEEV), a rare but deadly defense, and production of hormones. Recently, disease of the Atlantic and Gulf states. He is scientists discovered that this layer also secretes of Note also principal investigator on a $1.2 million U.S. tiny, bubble-like vesicles containing RNA into the Department of Defense (DOD) grant to develop a mother’s bloodstream. By analyzing this RNA, novel, inactivated vaccine to counter three strains researchers hope to better monitor placental of alphavirus, which comprise about 30 different health. A team including Pitt and Magee-Womens mosquito-transmitted viruses. Klimstr­ a will work Research Institute (MWRI) researchers are with investigators at Washington University in collaborating with researchers at Carnegie Mellon St. Louis and Oregon Health and Science Univer- University, Penn State University, and Massa- sity. An additional grant from the DOD is being chusetts Institute of Technology in developing used to investigate how mosquito-borne viruses “acoustic tweezers” that use sound waves to gain entry into the brain, while another was used separate placental vesicles based on their size to explore harnessing anti-EEEV antibodies and other properties. The research project is from cows that have been genetically altered to one of the 19 selected by the Eunice Kennedy produce human antibodies. Shriver National Institute of Child Health and Human Development (NICHD), National Insti- tutes of Health, that comprise the five-year Human Placenta Project. For the fiscal year,NICHD UPCI’S COMPREHENSIVE CANCER CENTER com­mitted approximately $46 million to the DESIGNATION RENEWED effort, with Pitt receiving more than$3.5 million. Placental function is key to fetal development and The National Cancer Institute (NCI) renewed the maintaining­ the health of the mother and baby. University of Pittsburgh Cancer Institute’s (UPCI) Monitoring for signs of dysfunction can indicate accreditation as a Comprehensive Cancer Center common pregnancy complications, said principal and one of just 45 NCI-designated Comprehen- investigator , Distinguished Yoel Sadovsky, MD sive Cancer Centers in the United States. The Professor of Obstetrics, G­ ynecology, and Repro- renewal comes with a Cancer Center Support ductive Sciences, Elsie Hilliard Hillman Professor Grant Parent Award totaling $25.6 million. “The of Women’s and Infants’ Health Research, and award recognizes our strength in basic, clinical, MWRI director. “A fundamental challenge in peri- and population research; education; and commu- natal medicine arises from our limited ability nity outreach and reflects the dedication of to diagnose placental disorders in real time everyone here who is working toward a future throughout the pregnancy.” Researchers hope without cancer,” said Nancy E. Davidson, MD, the new technique will help track placental health Distinguished Professor of Medicine, Hillman in real time and shed more light on placental func- Professor of Oncology, professor of pharma- tion and its effect on mothers’ and babies’ health. cology and chemical biology and of clinical and translational science, and UPCI director. In 2015, UPCI received $68 million in funding from NCI to support cancer research. Since the last renewal, CENTER FOR VACCINE RESEARCH UPCI program members, including the 337 Pitt RECEIVES FEDERAL GRANTS FOR faculty members, have collectively published MOSQUITO-BORNE VIRUSES RESEARCH more than 6,000 articles in peer-­reviewed jour- nals. UPCI was established in 1985, received Researchers at Pitt’s Center for Vaccine Research NCI-designated Comprehensive Cancer Center (CVR) received nearly through five $4 million status in 1990, and has retained it since. federal grants to study a variety of ­mosquito-borne viruses and further develop vaccines to fight their associated diseases. The research will be conducted in Pitt’s Regional Biocontainment Laboratory, a high-securit­ y facility that can safely contain and handle dangerous pathogens. Inci- dence of the related diseases remains small, yet they’re a significant threat, saidWilliam B. ­Klimstra, PhD, associate professor of micro­ biology and molecular genetics at the CVR. “While the number of people who get these

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 35 RESEARCH FUNDING AND SUPPORT, RESEARCH SPOTLIGHT

development, and academic achievement; and PITT INFECTIOUS DISEASE RESEARCHERS GRANT SUPPORTS DEVELOPMENT OF DRUGS factors that influence substance use. The Pitt HELP GUIDE HIV DRUG ROLLOUT IN AFRICA TO COUNTERACT RADIATION EXPOSURE team also includes David A. Lewis, MD, Thomas Detre Professor of Academic Psychiatry and chair Around 25 million people in sub-Saharan Africa Pitt’s multidisciplinary Center for Medical of psychiatry, School of Medicine, and profes- have HIV, representing nearly 70 percent of the Countermeasur­ es against Radiation has previ- sor of neuroscienc­ e, Dietrich School of Arts global total. As part of a plan for a large-scale ously developed and patented two drugs to miti- and Sciences;­ Rolf Loeber, PhD, Distinguished rollout of drugs and microbicides in that region gate the effects of radiation on the body. Now, Emeritus Professor of Psychiatry, School of to prevent HIV infection, Pitt infectious disease researchers are working to develop new drugs Medicine; and Beatriz Luna, PhD, Staunton researchers have been tasked with monitoring and are exploring methods to administer drugs Professor of Pediatrics and Psychiatry, School of for drug resistance. With a agreement individually or in combination using microneedle $5 million Medicine, and professor of psychology, Dietrich from the U.S. Agency for International Devel- arrays. These new efforts are propelled by a five- School of Arts and Sciences. “This will be the first opment, researchers from the Department of year grant from the National Insti- $18.7 million research project to study such a large group of Medicine’s Division of Infectious Diseases— tute of Allergy and Infectious Diseases (NIAID) individuals from early in development, when most including project director , to the School of Medicine, the University of Pitts- John W. Mellors, MD would not have used drugs, to possibly peak use Global Elimination of HIV and AIDS Professor, burgh Cancer Institute, and Pitt’s Graduate School in adolescence and to explore different pathways professor of medicine and of pathology, chief of Public Health to develop drugs that can protect that contribute to decreases in substance use of the Division of Infectious Diseases, School of against radiation from deliberate attacks or acci- with maturation,” Luna said. Medicine; professor of infectious diseases and dental exposure. It marks the third renewal of microbiology, Graduate School of Public Health; the grant for Joel S. Greenberger, MD, Claude and Urvi M. Parikh, PhD, assistant professor Worthington Benedum Foundation Professor and of medicine — will conduct research to develop chair of the Department of Radiation­ Oncology. RESEARCH ON HIV AND ACCELERATED AGING evidence-based policies for monitoring drug “Patients suffering from radiation disease may HIGHLIGHTED BY TWO GRANTS resistance during HIV-drug distribution. Pre-­ be too sick to take an oral therapy, and ­deliver­ing exposure prophylaxis (PrEP) and antiretroviral drugs intra­venously would be too impractical People with HIV can live for decades thanks (ARV)-based microbicides will be provided via and costly. We need a safe and effective way to to medication, yet they’re more likely to have daily pills or a monthly vaginal ring that releases make sure these drugs are given appropriately,” cardiovascular, lung, kidney, and liver diseases, medication. Should someone become infected Green ­berger said. The researchers are also inves- osteoporosis, and other conditions compared with HIV while on PrEP or an ARV-based micro- tigat­ing molecular mechanisms behind radiation to healthy peers; their bodies often resemble bicide, a drug-resistant strain could arise and disease. In addition to emergency preparedness, someone years or even decades older. A spread. The project will assess the frequency of such drugs might be used to lessen side effects $3 million grant from the National Heart, Lung, drug resistance and develop strategies to reduce of radiation therapy for head and neck cancer and Blood Institute will permit investigators at it. The researchers are also developing models patients. Pitt’s Center for Vaccine Research to study the and simulations to analyze the costs, frequency, accelerated-aging characteristics and processes and effectiveness of regularHIV testing for popu- linked to HIV infection. Ivona Pandrea, MD, PhD, lations at risk. They will later advise the World professor of pathology, School of Medicine, and Health Organization and the Joint United Nations LONG-TERM STUDY TO TRACE IMPACT OF of infectious diseases and microbiology, Gr­ aduate Programme on HIV/AIDS on PrEP and microbicide SUBSTANCE USE ON BRAIN DEVELOPMENT School of Public Health, and grant principal inves- prevention initiatives. tigator, and colleagues will research the relation- Pitt Department of Psychiatry investigators are ship between excessive blood clo­ tting — which is joining the multi-site Adolescent Brain ­Cognitive common and often deadly for HIV patients — and Development (ABCD) Study that plans to follow accelerated aging. Cristian Apetrei, MD, PhD, SPORE GRANT RENEWAL EXPANDS HEAD more than 10,000 9- and 10-year-old children for professor of microbiology and molecular genetics, AND NECK CANCER RESEARCH 10 years to study the developing brain — from School of Medicine, and of infectious diseases early years, through adolescence, and into young and microbiology, ­Graduate School of Public Incidence of differentiated thyroid cancer is rising adulthood— and how it’s affected by marijuana, Health, is principal investigator on another at a faster rate than all cancers in the United alcohol, and other drugs. Due to inconsistent $3.3 million National Institute of Allergy and States and worldwide. With a findings in smaller studies, the NIH provided $10.9 million Infectious Diseases grant to explore reacti- grant renewal from the National Cancer I­nstitute’s $30 million per year for the ABCD Study to vating cellular reservoirs for HIV in the body. Specialized Program of Research Excellence comprehensively investigate brain changes, said Reactivating the virus could reduce the size of (SPORE), Pitt researchers will continue to explore ­ , professor of psychi- Duncan B. Clark, MD, PhD the reservoir and lead to virus eradication from differentiated thyroid cancer and other head and atry, School of Medicine, and leader of the local the infected individuals. neck cancers. The thyroid cancer project will use research site, where more than 500 Pittsburgh next-generation sequencing to reduce unneces- children are expected to participate. The funding sary surgeries for less aggressive tumors while will support 19 research sites across the United helping identify patients with more aggressive States, with Pitt receiving $5 million total, and the disease. Three of the four projects outlined by this study will address the effects of regular­ versus SPORE grant focus on head and neck squamous occasional substance use on brain development;­ cell carcinoma, an often deadly cancer with few substance use and mental illness, physical health, drug ­therapies. The award is one of four SPORE grants active at Pitt. The others support mela- noma, lung, and ovarian cancer research.

36 PITT TO COORDINATE, MANAGE A NUMBER OF CLINICAL TRIALS TARGETING Pitt-Developed Test Has Potential To Diagnose BREATHING DISORDERS Myriad Conditions with Drop of Blood The University of Pittsburgh’s School of ­Medicine and Graduate School of Public Health are leading a $16.8 million, five-year federal initiative to oversee national clinical trials to develop new unique way of detecting antibodies in blood introduces the possibility of treatments for a variety of breathing disor­ ders. new diagnostic test development for autoimmune diseases, cancers, and With funding from the National Heart, Lung, and other conditions for which causes are elusive, according to U­ niversity Blood Institute, National Institutes of Health, of Pittsburgh research. researchers will conduct clinical studies on As reported in the August 2016 edition of the Journal of Immunological chronic lung conditions such as interstitial lung Methods, the proof-of-principle study demonstrates the first evidence disease, chronic obstructive pulmonary disease on which to base development of a potential blood test for any infec- (COPD), pulmonary hypertension, and obstruc- tious disease by screening random libraries of non-biological molecular shapes. tive sleep apnea. Chronic lung diseases comprise A“The method does not rely on starting with known viral components,” said some of the most common medical conditions senior author Donald S. Burke, MD, Graduate School of Public Health dean and worldwide, and more than 15 million people in the Distinguished University Professor of Health Science and Policy. “This is important United States alone suffer fromCOPD . A Network because there are conditions for which there isn’t a known antigen, such as newly Management Core headed by Pitt will coordinate emerged epidemics, auto­immune diseases, or even responses to traumatic injury.” and support trials carried out by the Pulmonary When confronting antigens caused by infectious disease or injury, the immune Trials Cooperative, which includes lung disease system produces antibodies which, like puzzle pieces, can fit themselves to mole- researchers from across the nation. cules on the invader or damaged tissue by shape. Pitt researchers used a technique pioneered by coauthor Thomas Kodadek, PhD, of the Scripps Research Institute, that can synthesize differing molecular shapes (called “peptoids”) that are then attached to microscopic plastic beads. These U.S. DEPARTMENT OF DEFENSE peptoids are not organic, but if they match to the corresponding shape on an anti- PROMPTS ALPHAVIRUS BIOTERRORISM body, that antibody will connect to them, allowing the scientist to pull out each bead COUNTERMEASURES and examine the peptoids and their corresponding antibodies. Burke’s team chemically generated a huge library of random molecular shapes. The U.S. Department of Defense (DOD) has Researchers then used blood from HIV-infected and uninfected people to screen consistently funded a range of research initia- 1 million candidate shapes to identify those binding to antibodies present in the blood tives under way at Pitt’s Center for Vaccine of HIV-infected patients but not the healthy controls. Despite the fact that no HIV Research (CVR). With a recently awarded proteins or structures were used to construct or select the peptoids, the approach $7.6 million grant to explore countermeasures successfully detected the best molecular shapes to use in screening for HIV antibodies. against bioterrorism attacks, CVR investigators The team subsequently synthesized mass quantities of the HIV-antibody-targeting aim to home in on developing drugs and vaccines peptoid and tested it by screening hundreds of samples from the Multicenter AIDS to counter alphaviruses, which comprise about Cohort Study (MACS), a confidential research study of the natural history of treated 30 mostly mosquito-transmitted viruses. The and untreated HIV/AIDS in men who have sex with men. Study coauthor Charles group includes eastern, western, and V­ enezuelan Rinaldo, PhD, chair of Pitt Public Health’s Department of Infectious Diseases and equine encephalitis viruses, which are rare yet Microbiology, and director of the Pittsburgh arm of the MACS, selected the samples highly deadly and cause natural outbreaks in but blinded the testers to which samples were positive or negative for HIV. The test the Americas. The alphaviruses’ potential use distinguished between the samples of HIV-positive blood and HIV-negative blood as bio­weapons has prompted the researchers with a high degree of accuracy. to better understand the biological mechanisms “This technology means that we may be able to take a single drop of blood from through which the viruses harm people upon a patient and detect antibodies to all manner of infections, cancers, or other condi- inhalation. They’re also working to determine tions to which they’ve been exposed. We hope that this is the first step toward devel- the best timing for providing antiviral medications opment of an ‘Epi-chip’ that can be used to reconstruct a person’s entire exposure and are exploring therapies that could be tested in history,” said Burke, who is also UPMC Jonas Salk Professor of Global Health. human clinical trials, said ­coprincipal investigator Amy L. Hartman, PhD, assistant professor of infectious diseases and micro­biology, Graduate School of Public Health, and grant principal inves- “We hope that this is the first step tigator. She’ll work alongside colleagues, including coprincipal investigator William B. Klimstra, toward development of an ‘Epi-chip’ PhD, associate professor of microbiology and that can be used to reconstruct molecular genetics. a person’s entire exposure history.”

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 37 RESEARCH INNOVATIVE THINKING, FUNDING AND SUPPORT

When It All Goes Wrong: Surgical Rescue as a Discipline

n call one Saturday a little more than two years ago, surgeon Andrew B. Peitzman, MD, had an epiphany. Peitzman spent that whole Saturday in surgical suites at UPMC Presbyterian Hospital attending to complications of operations or procedures done previously at Presby and at facilities throughout the region. While unexpected and serious compli- Ocations can arise during or after any surgery, risks are greater for patients undergoing emergency operations. “It struck me that this was probably the most vulnerable population for whom we provide care,” says Peitzman, Mark M. Ravitch Professor of Surgery and Distinguished Professor of Surgery, School of Medicine. Fully two-thirds of UPMC Presbyterian patients arrive as trans- fers from other facilities that initiated emergency or other surgical care, he explains. “What we’re doing is trying to identify who these patients are and what to do to get them out of trouble.” In two recent publications, Peitzman describes these cases in terms of “surgical rescue,” requiring immediate intervention — and, in the majority of cases, additional surgery. Saving these critically ill patients requires a skilled team with access to resources that include immediate availability “Almost any patient will tolerate of operating rooms, intensive care expertise, surgeons prac- a well-thought-out, well-done ticed in treating complicated, “reoperative” surgery, and broad surgical subspecialty support, Peitzman and colleagues write operation. What they don’t tolerate in the September 2015 Scandinavian Journal of Surgery. is that first complication.” “As acute-care surgeons, we’ve taken care of patients with these complications, but nobody has focused on it as a unique problem,” he says, explaining that medical or surgical compli- cations account for more than 1 million hospitalizations a year in the United States. Although diagnoses that require surgery vary, these most fragile of patients are more likely to be older with underlying health issues. “Almost any patient will tolerate a well-thought-out, well-done operation. What they don’t tolerate is that first complication,” Peitzman continues, quoting Richard L. Simmons MD, Distin- guished Professor of Surgery and emeritus department chair. Effective surgical rescue requires vigilance for symptoms like elevated white count or generalized decline and early recogni- tion that additional surgery is mandatory to save these patients. “There should be no delaying and hoping these issues won’t turn into a more serious problem,” he says.

38 in blood and cerebrospinal fluid, structural and NARSAD GRANTS FURTHER BIPOLAR DISORDER BIG DATA ANALYSIS A TOOL FOR PREDICTING functional MRI scans, and cognitive and func- AND MENTAL HEALTH RESEARCH CANCER METASTASIS AND DEVELOPMENT tional measures in 180 individuals with Down syndrome and 40 without. Individuals with Down The Brain and Behavior Research Foundation Researchers can analyze a set of mutated genes syndrome have three copies of chromosome 21, provided two National Association in a cancerous tumor and use the raw data as $100,000 each of which contains a copy of the gene linked for Research on Schizophrenia and Depression predictors of cancer outcomes, such as recur- to the precursor protein for beta-am­ yloid, which (NARSAD) Independent Investigator Grants to rence and metastasis. However, with devel- is heavily present in the brains of Alzheimer’s Pitt Department of Psychiatry faculty members opments in data analysis based on machine patients. “It’s apparent from Down syndrome who will use the awards to further research on learning, an alternative approach involves find- patients that amyloid deposition is not suffi- molecular rhythms and psychiatric disorders and ing patterns in the data that represent biological cient to produce dementia,” Handen said. “These on sleep disturbance in adolescents with bipolar processes, such as aberrant cell signaling path- individuals have these deposits for more than disorder. Studies have revealed that bipolar ways, and using those ­patterns to predict cancer a decade before cognitive decline is apparent. disorder, major depression, and schizophrenia are outcomes. Moreover, the combined use of bio- Understanding the relationships between Down associated with significant disruptions to circa- logical patterns and clinical data holds promise syndrome, disease biomarkers, and cognitive dian rhythms. Disruptions to normal circadian to further improve such predictions, which can decline is critically important to help us design rhythms have also been known to trigger mood affect clinical care. To advance this work, Big Data better therapies for all people with Alzheimer’s.” changes and psychotic episodes. Pitt researchers, researchers at Pitt received a $5 million, three- led by Colleen A. McClung, PhD, associate year grant to develop better methods to ana- professor of psychiatry, will explore whether lyze and model large amounts of cancer-patient­ such alterations are present at the molecular data. Pennsylvania’s Department of Health pro- HEART ASSOCIATION GRANT SPURS level in human brain regions that regulate mood vided this Commonwealth Universal Research INVESTIGATION OF LATER-LIFE and cognition. They will investigate if stabilizing Enhancement, or CURE, grant as part of the Big CARDIO ­VASCULAR DISEASE IN WOMEN rhythms can lead to therapeutic advancements. Data for Better Health (BD4BH) project, which The research will also help investigators to deter- also includes UPMC, Carnegie Mellon University, During pregnancy, women normally undergo mine the importance of molecular rhythmicity the Pittsburgh Supercomputing Center, and striking metabolic and cardiovascular adaptive in the primary pathology of psychiatric disor- Lincoln University. While the investigators will changes that help to ensure that their babies ders. , assistant professor focus on breast and lung cancers to develop Peter L. Franzen, PhD develop and grow normally and are carried of psychiatry, will use support from the award analytical software and tools, their methods can to term. Magee-Womens Research Institute to lead research on the neural mechanisms by apply to other diseases, said Gregory F. Cooper, (MWRI) researchers study these pregnancy which sleep disturbance ­influences suicide risk , professor of biomedical informatics, MD, PhD changes to look for abnormalities that may and treatment response to adjunctive dialec- of computational and systems biology, School of signal a predisposition­ to later-life cardio­ tical behavioral therapy (DBT) in youths with Medicine, and of clinical and translational science. vascular disease (CVD) in women. With a four- bipolar disorder. DBT is hypothesized to signifi- “The basic approach is to process raw ­molecular year $3.7 million grant from the American Heart cantly improve suicidality and mood symptoms data, such as gene sequence and expression data, ­Asso­ciation, the MWRI researchers will investi- by enhancing emotion regulatory capabilities; to derive highly informative biological patterns gate whether certain blood vessel changes that sleep disturbance is hypothesized to disrupt this in the data that are then used along with clinical occur during pregnancy can point to mechanisms activity. The research also builds on Franzen’s data to predict patient outcomes. We are evaluat- behind CVD in women. They hope to also help collaboration with , asso- ing the hypothesis that this approach will predict Tina R. Golds­ tein, PhD develop treatments for and better identify women ciate professor of psychiatry, to examine the cancer outcomes significantly better than current at risk for CVD. Heart disease can damage the neural circuitry underlying emotion regulation methods,” Cooper said. inner walls of blood vessels and lead to spasms and cognitive control via functional magnetic and decreased blood flow to the heart muscle, ­resonance imaging (fMRI) in bipolar participants which is known as microvascular dysfunction, a at baseline and mid-treatment. potentially u­ ndetected condition. “Micro­vascular PROGRESSION OF ALZHEIMER’S DISEASE dysfunction is a devastating public health chal- IN INDIVIDUALS WITH DOWN SYNDROME lenge, because almost two-thirds of women who EXPLORED IN MULTI-SITE STUDY die suddenly of coronary heart disease have had no previous symptoms. We hope to build Adults with Down syndrome typically show on the research of our previous studies by iden- symptoms of Alzheimer’s by their 40s and have tifying mechanisms of CVD in women that are a 70 to 80 percent chance of developing clinical unmasked or perhaps affected by adverse preg- dementia by their 60s, said Benjamin L. Handen, nancy outcomes,” said Carl Hubel, PhD, MWRI , professor of psychiatry and coprincipal PhD investigator and associate professor of obstetrics, investigator on a , five-year grant $12.5 million gynecology, and reproductive sciences. from the National Institute on Aging, National Institutes of Health. The grant will enable Alzhei- mer’s disease research experts to better explore Alzheimer’s biomarkers and cognitive function in people with Down syndrome. Pitt is one of four sites in the United States and the United Kingdom taking part in the Neurodegeneration in Aging Down Syndrome study funded by the grant. The study will monitor and track amyloid

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 39 RESEARCH FUNDING AND SUPPORT

NIH Director’s New Innovator Award Funds Study of Physician Decision-Making “I ARGUE THAT INTUITION OFTEN FORMS THE BASIS OF PHYSICIAN DECISION- n critical care medicine, the difference between life and death can often be measured in the treating physicians’ MAKING—PARTICULARLY split-second decisions. For Deepika Mohan, MD, MPH, IN CRITICAL CASES LIKE assistant professor of critical care medicine and of surgery, TRAUMA TRIAGE, SEPSIS, the most important question isn’t which decisions are AND STROKE. PEOPLE made — but why. “Most efforts to reduce physician error begin with the REMEMBER STORIES— idea that decisions reflect knowledge, attitudes, and external IF A VIDEOGAME CAN Iconstraints,” she says. “I argue that intuition often forms the ALLOW US TO RECALI- basis of physician decision-making — particularly in critical cases like trauma triage, sepsis, and stroke.” BRATE INTUITION, IT CAN Mohan is studying ways to possibly improve the decision- BE A NEW TOOL TO HELP making process with funding from a five-year, $2.3 million PEOPLE MAKE THE RIGHT National Institutes of Health Director’s New Innovator Award, one of 41 awarded by NIH in 2015 to fund “unusually creative DECISIONS FASTER.” new investigators with highly innovative research ideas” early DEEPIKA MOHAN, MD, MPH in their careers when supportive data for an R01 application may be scarce. Her study, “A Novel Intervention To Make Heuristics a Source of Power for Physicians,” uses game technology to translate behavioral science principles about how people learn into a new method of modifying physician judgment. A videogame, called “Night Shift,” has been developed by Pittsburgh-based Schell Games for use in a random- ized, controlled trial during a 2016 American College of Emergency Physicians conference. Players will be asked to play the game or an educational control followed by a virtual simulation, to see which intervention has an effect on choices made during the simulation. “People remember stories,” says Mohan. “If a videogame can allow us to recalibrate intuition, it can be a new tool to help people make the right decisions faster.”

40 reveal novel biomarkers that will be useful for HARRINGTON SCHOLAR AWARD STAND UP TO CANCER AWARDS predicting which DCIS are likely to progress. We SUPPORTS LUNG TRANSPLANTATION TWO PITT INVESTIGATORS can then offer personalized therapy to those who RESEARCH require intervention while reducing the overtreat- Two Pitt investigators each received $750,000 ment of DCIS in those who don’t,” said Adrian Every year, the Harrington Scholar-Innovator Innovative Research Grants in April from Stand Lee, PhD, professor of pharmacology and chem- Program of the Harrington Discovery Institute Up to Cancer, which funds scientists and clin- ical biology, School of Medicine,­ and of human selects up to 10 physician-scientists to receive ical trials engaged with cancer research, among genetics, Graduate School of Public Health. Harrington Scholar-Innovator awards, which other initiatives. Greg M. Delgoffe, PhD, assis- provide funding to help researchers bridge tant professor of immunology, will continue basic discoveries into clinical practice. Rama K. research on immunotherapy techniques that ­Mallampalli, MD, UPMC Professor of Acute Lung alter the tumor microenvironment. He will explore ST. BALDRICK’S FOUNDATION FUNDS Injury; chief of the Division of Pulmonary, Allergy, cancer-fighting measures that employ oncolytic CHILDHOOD LIVER CANCER RESEARCH and Critical Care Medicine, Department of Medi- viruses, which are re-engineered to alter the cine; and professor of medicine and of cell biology, immunosuppr­ essive nature of the tumor micro- Cancer cells alter their metabolism to provide was named a 2016 Scholar­ -Innovator. With up to environment and can infect and destroy tumor the energy and metabolic building blocks needed $700,000 in support, Mallampalli will continue to cells. By improving and evaluating simultaneous to support their rapid division, said Edward V. advance his research surrounding lung transplan­ use of two effective types of immunotherapies, Prochownik, MD, PhD, professor of pediatrics tation. He aims to assess the efficacy of a lead Delgoffe and colleagues hope for a more potent and director of oncology research at Children’s compound that inhibits a protein involved with immune response when testing them against Hospital of Pittsburgh of UPMC. By observing how acute cellular rejection during lung transplanta- melanoma in laboratory mice and, hopefully, these cells generate their energy, Prochownik tion. Acute cellular rejection is strongly associated in patients. , assistant Kara A. ­Bernstein, PhD hopes to advance new ways of mitigating tumor with chronic allograft rejection, which can impede professor of microbiology and molecular genetics, growth. He is the recipient of a $100,000 research long-term success after lung transplantation and will further her research on double-strand break grant from the St. Baldrick’s ­Foundation, a charity lead to allograft loss and death. repair proteins, which are vital for fixing DNA dedicated to raising money for ­pediatric oncology damage and preventing cancer. Her research research and clinical trials. The award is one of focuses on double-strand break repair proteins 70 grants distributed nationally and internation- known as RAD51 paralogs and their function. She ally by St. Baldrick’s. Prochownik and colleagues RESEARCHERS TO PINPOINT HOW will continue to explore how mutations in the have identified some of the key mechanisms and THE ANIMAL NOSE LOCALIZES SMELL RAD51 paralogs may lead to cancer development processes that enable cancer cells to change their and assess new methods for treating patients metabolism. He and his research team developed The animal nose and brain can detect the smell of harboring RAD51 paralog mutant tumors. a model of hepatoblastoma, the most common mates and food. It enables bloodhounds to track childhood liver cancer. They found that the mito- the scent of a missing person or rats to find land- chondria of the hepatoblastoma cells appear to be mines in Angola. Yet we don’t fully understand reprogrammed to operate at maximum capacity, the olfactory system, said coprincipal investi- 3D BIOPRINTED BREAST DUCT MODEL providing significant resources for cells to rapidly gator , professor of neuro- AIMS TO LIMIT OVERTREATMENT Nathan Urban, PhD grow and divide. These metabolic changes biology, and doing so could enable the creation OF NONINVASIVE BREAST CANCER correlate with loss of expression of the mitochon- of artificial chemical detection systems and a drial sirtuins, SIRT3 and SIRT4. By finding ways better understanding of other sensory systems. Improvements in mammography screening have to re-express SIRT3 and SIRT4, the researchers To investigate how the animal nose can localize resulted in better detection of invasive breast hope tumor growth and toxicity from currently smells, Pitt researchers received a cancer but have also meant increased detection $6.4 million used therapies can be suppressed. three-year National Science Foundation grant of noninvasive breast cancer, such as ductal carci- as part of a multi-institutional project to explore noma in situ, or DCIS, the earliest form of breast sense of smell. Localizing where a smell is coming cancer, in which the cancer is still contained from is challenging, because it requires sampling in the milk duct. With a two-year, $800,000 odors that waft through turbulent air a distance grant from the U.S. ­Congressionally Directed away from their origin. Thus, the multidisciplinary Medical Research Program of the Depart­ment research team includes experts in mathematics, of Defense, University of ­Pittsburgh Cancer Insti- airflow physics, neuroscience, and evolutionary tute researchers and Carnegie­ Mellon University biology who are constructing models to quan- biomedical engineers are creating a 3D bioprinted tify odors and are using algorithms to model breast ductal structure to advance identification their dispersal. The researchers believe these of low-risk lesions that may not require invasive models could be useful for national security and treatment. The researchers are growing DCIS cells law enforcement by helping to improve methods in a printed mouse-replica breast ductal system for detecting explosives and could also advance and exploring why some DCIS cases progress to the development of technologies that inhibit the invasion while others remain static. More than flight navigation of disease-carrying mosquitos 60,000 women are diagnosed with DCIS each and crop pests. year in the United States, and the majority of cases will not progress to invasive diseases even if left untreated. However, many such women receive unnecessary surgeries, treatments, and therapies. “Our hope is that our research will

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 41 RESEARCH INVESTIGATIONS AND REVELATIONS

SCIENCE TRANSLATIONAL MEDICINE

AUG 2015 \ VOL 7 \ ISSUE 299 DIGITAL SIGNATURE OF CILIA MOVEMENT MAY HELP Publications DIAGNOSE CILIARY DISORDERS of Note Cilia, the tiny, hair-like projections on cells that line nasal passages, the lungs, and other tissues can experience improper, irregular motion. Such ciliary motion (CM) defects can result in respiratory airway issues and even congenital heart disease. Doctors currently identify CM defects using video-microscopy or electron microscopy. “Visual reviews like these can be subjective, time consuming, and error prone,” said senior investigator Chakra Chennubhotla, PhD, associate professor of computational and systems biology. He and colleagues developed a system to computationally quantify and create a digital signature of cilia movement, from beat pattern to rotational breadth to synchronicity. The research team used data from UPMC ANGEWANDTE CHEMIE Children’s Hospital of Pittsburgh of and from Children’s National Medical Center in Washington, D.C., to quantify cilia from patients with

JAN 2016 \ VOL 55 \ ISSUE 1 congenital heart disease or primary ciliary dyskinesia (PCD), as well as from healthy individuals. To test effectiveness, researchers screened “HOT PAPER” DESCRIBES NEW PROCESS FOR random samples for PCD; their computational tool correctly identified more DISTANCE MEASUREMENT IN PROTEINS than 90 percent of the PCD cases. It’s hoped that a clinical trial can allow researchers to upload videos of patients’ nasal linings for assessment by The editors of the journal of the German Chemical Society, Angewandte this technique, said Cecilia Lo, PhD, Dr. F. Sargent Cheever Professor and Chemie, designate “hot papers” to highlight important findings in rapidly chair of developmental biology and professor of pediatrics and of clinical evolving fields of high interest. In early 2016, the journal selected a paper and translational science. “This approach may, in the future, serve as a by Angela M. Gronenborn, PhD, Distinguished Professor of Structural rapid first-tier screen to identify at-risk patients,” Lo said. Biology, UPMC Rosalind Franklin Professor and chair of the Department of Structural Biology in the School of Medicine. Structural biology is a field at the intersection of molecular biology, biochemistry, and biophysics, where scientists like Gronenborn, who is TRENDS IN BIOCHEMICAL SCIENCES also a professor of bioengineering, explore the molecular structure of biological macromolecules, especially proteins and nucleic acids. She MAY 2016 \ VOL 41 \ ISSUE 5 and her colleagues seek to understand how these molecules acquire the OVERVIEW OF RETROVIRUS CAPSID RESEARCH LAYS structures they have and how changes in structure affect function. This PATH FOR CONTINUED INVESTIGATION information is of great importance to biologists, because proteins and nucleic acids carry out most cellular functions. One important element of Gronenborn’s work involves obtaining precise In retroviruses, the capsid is involved with almost all stages of the life distance measurements in proteins. In her recent publication with research cycle, from early stages of post-entry to maturation of the viral particle. associate Elena Matei, PhD, Gronenborn describes using fluorine NMR Capsid cores self assemble and house the viral genome, as well as several paramagnetic relaxation enhancement as a technique to extract distance proteins that drive infection. The cores protect the viral genes so that they information in F-labeled proteins. The researchers found that the process can enter the host’s nucleus. Angela M. Gronenborn, PhD, Distinguished provides a superior alternative to more traditional methods of distance Professor of Structural Biology and UPMC Rosalind Franklin Professor extraction since it is not hampered by background noise. Therefore, it is and chair of structural biology, recently provided an overview of findings particularly well-suited to large proteins, protein complexes, and membrane surrounding the retroviral capsid cores and how their structure and prop- proteins — making it a useful tool that could lead Gronenborn and her erties contribute to viral infection. Capsid cores follow defined geometric colleagues to new insights into HIV pathogenesis. rules; and understanding their precise shape and molecular structure, particularly at assembly interfaces, opens new possibilities for drug devel- opment. Further, elucidating the interactions and relationships between structure, dynamics, and function of capsid assemblies — studies that are under way in the Pittsburgh Center for HIV Protein Interactions — requires deciphering the interfaces between subcomponents and building blocks in order to map out detailed atomic models of the core, both alone and with interacting cellular components. It is anticipated that the results of such studies will yield new understanding that may advance targeted therapies.

42 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES

AUG 2016 \ VOL 113 \ NO 35 NEURAL CONNECTIONS MAY HELP EXPLAIN PSYCHOSOMATIC ILLNESS

Imagine that moment when you take your seat on a roller coaster — the big one with the agonizingly slow climb to the top and the terrifying plunge that follows. As the seatbelt clicks into place and you grip the bar in front of you, you will experience a rush of physiological responses to this situation. Roller coaster aficionado or not, everyone has experienced the adrenaline rush that is our natural response to fear or stress. Elevated heart rate, sweating, and pupillary dilation occur when our adrenal glands, which are right above the kidneys, are triggered by sympathetic neurons in the spinal cord to secrete hormones. Though it’s often called our “fight or flight” response, most of us in line at Kennywood will do neither. We try to breathe normally and think positive thoughts. Clearly, our individual response to stress is subject to extensive “top-down” or cognitive control. Yet scientists have never been able to point to any neural networks that would permit the “mind,” generally associated with the cerebral cortex, to influence the involuntary endocrine responses that control internal organs — until now, that is. In a groundbreaking study published in Proceedings of the National Academy of Sciences, researchers from Pitt’s Brain Institute, Department of Neuro­biology, Systems Neuroscience Institute, and Center for the Neural Basis of Cognition used an experimental strain of rabies virus, which infects neurons and can be used to trace neural networks, to identify the areas of the primate cerebral cortex that communicate through multi-syn- aptic connections with the adrenal medulla, the inner part of the adrenal gland. Led by Peter L. Strick, PhD, Thomas Detre Professor of Neuro­science, Distinguished Professor and chair of neuro ­biology, professor of neurological surgery and of psychiatry, the team showed that two broad networks in the cerebral cortex have access to the adrenal medulla. One is an area involved in all aspects of skele­tomotor control, including the selection of a physical response to a situation, preparation to act, and move­ ment execution. Another is involved in higher order aspects of thinking and experiencing emotion. These results indicate that specific circuits exist to link movement, cognition, and affect to the function of the adrenal medulla. This circuitry may help explain the effects of internal states like chronic stress and depression on organ function and thus provide a concrete neural substrate for unexplained phenomena such as psychosomatic illness, which scientists have long viewed with suspicion.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 43 RESEARCH INVESTIGATIONS AND REVELATIONS

JAMA PEDIATRICS

NOV 2015 \ VOL 169 \ ISSUE 11 E-CIGARETTE USE IS A GATEWAY TO TRADITIONAL SMOKING AMONG YOUNG ADULTS

Compared with those who do not use e-cigarettes, young people who use e-cigarettes are significantly more likely to start smoking actual cigarettes within a year, according to a study led by the University of Pittsburgh Center for Research on Media, Technology, and Health (CRMTH) and the Dart- mouth-Hitchcock Norris Cotton Cancer Center. The research team analyzed data from a national sample of about 700 nonsmoking 16- to 26-year-old e-cigarette users and nonusers. At baseline, the participants all answered with “definitely no” after being asked in a 2012 survey if they would try a cigarette offered by a friend or if they believed they would smoke a cigarette within the next year. However, in a follow-up 2013 survey, 38 percent of the e-cigarette users had started smoking traditional cigarettes compared with only 10 percent of the nonusers. “These differences remained statistically significant and robust even when we controlled for multiple known risk factors for initiating cigarette smoking, such as age, sex, race, ethnicity, NATURE COMMUNICATIONS socioeconomic status, sensation seeking, parental smoking, and friend smoking,” said Brian A. Primack, MD, PhD, professor of medicine and of JUL 2015 pediatrics, director of CRMTH, and assistant vice chancellor for research on health and society, health sciences. The study was the first to examine this STUDY EXAMINES PROTEIN IN YEAST TO ELUCIDATE association in a national sample of young people and to include people older DNA REPAIR PROCESSES SURROUNDING CANCER than 18. The researchers plan to continue monitoring usage of e-cigarettes and cigarettes so that policymakers can create research-based regulations Protein mutations in the RAD51 paralogues are associated with to mitigate e-cigarettes’ gateway potential. breast and ovarian tumors, according to Kara A. Bernstein, PhD, assistant professor of microbiology and molecular genetics. ­Bernstein was senior investigator on a study exploring how RAD51 paralogs function with other proteins to repair breaks in the DNA MOLECULAR PHARMACOLOGY strands. RAD51 paralogs were too complex to study in animal cells, so Bernstein and colleagues studied them in yeast. By studying the JUN 2016 \ VOL 89 \ ISSUE 6 yeast Shu complex, which contains RAD51 paralogs, the researchers NEWLY DEVELOPED COMPOUND COULD SPELL BETTER uncovered their function during repair of DNA strand breaks. The TREATMENT FOR EPILEPSY, TINNITUS RAD51 paralogs work with the Shu complex to find homologous DNA regions in which both strands of the twisting DNA ladder are broken due to toxins, radiation, or other influences, which can result Retigabine, a drug that has been used to treat epilepsy, can lead to side in missing chunks of genetic code. The proteins work together to effects like retinal abnormalities, urinary retention, and skin discoloration. repair the damage and fill in the pieces of missing genetic code In response, Pitt researchers have redesigned retigabine to effectively treat through a process called homologous recombination. “Now that epilepsy and deliver fewer potential side effects. The drug might also treat we understand what the proteins do, we can now design tailored tinnitus and other disorders associated with erratic and volatile neural therapies for patients who have cancer and mutations in these signaling, which characterizes epilepsy. Epilepsy drugs typically operate by repair genes,” said Bernstein. influencing the transport of sodium, potassium, and chloride ions across the nerve cell membrane to reduce brain cell excitability. “We have been able to refine an existing medication so that it acts selectively on certain nerve cell membrane transport channels, which should make it more effective,” said Thanos Tzounopoulos, PhD, Professor of Auditory Physiology and associate professor of otolaryngology. Retigabine activates four out of the five types of potassium channels in theKCNQ category. However, only two of the channels, KCNQ2/3, are critical for stabilizing the membranes of brain cells involved in hyperexcitability-related disorders, such as epilepsy and tinnitus, Tzounopoulos said. The newly developed compound, RL648_81 (RL-81), targets only those two channels. Researchers found that RL-81 is 15 times more potent than retigabine and should have fewer side effects. The compound might help reduce tinnitus by preventing hyperexcitation of nerve cells in auditory pathways, Tzounopoulos said.

44 JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY PLOS ONE

NOV 2015 \ VOL 73 \ ISSUE 5 NOV 2015 \ VOL 10 \ ISSUE 11 COMPUTER PROGRAM COMPARES SKIN LESION TEXT MESSAGE INTERVENTION PROGRAM SUSTAINS IMAGES TO DETECT MELANOMA REDUCED BINGE DRINKING BY YOUNG ADULTS

Each year in the United States, 76,000 people are diagnosed with mela­ In a first-of-its-kind program, text-message interventions have successfully noma, and 10,000 die from it. Since early detection is key to combating this reduced episodes of binge drinking in young adults, as demonstrated by a deadliest form of skin cancer, Pitt researchers partnered with UPMC and Pitt trial designed by lead author Brian Suffoletto, MD, assistant professor Carnegie Mellon University to create a computer program that compares of emergency medicine. After recruiting 18- to 25-year-olds discharged the image of a suspected spot on a patient’s skin against images of benign from several emergency departments across Western Pennsylvania who and malignant lesions. The program behind this noninvasive technique can had a history of hazardous drinking, the intervention program separated be run on a smartphone or tablet device and can help physicians determine them into three groups. The first group received text messages for 12 the lesion’s severity and whether a biopsy is needed. Researchers, as well weeks every Thursday inquiring about and prompting commitment to as dermatologists, calculated and assessed the severity of 173 dermoscopic limit weekend drinking plans, followed by texts on Sunday asking about images of skin lesions that had already been diagnosed. Of these, 39 were actual consumption and providing tailored feedback for self-reflection. melanomas, 14 were non-melanoma skin cancers, and 120 were benign. A separate self-monitoring group received texts each Sunday asking The computer program correctly detected melanoma in 97 percent of the participants to share how much they drank but received no feedback. cases, with specificity at 44 percent. Compared to evaluation by clinicians, A final control group received no texts. Nine months after enrollment, the program had a slightly higher rate of melanoma detection. The tool’s those who received text interventions reported one fewer drinking day per specificity, or ability to identify a harmless lesion as benign, was slightly month on average and a 12 percent reduction in binge drinking episodes lower than that of the clinicians. “Nothing is better than a board-certified overall compared to no reductions in the control and self-monitoring dermatologist evaluating your skin, but this study indicates that a computer groups. Alcohol-related injuries also declined in the intervention group. program … could be a valuable tool for physicians when deciding what to By incorporating automated communication and mobile technology, the do with a suspicious mark on the skin,” said Laura Korb Ferris, MD, PhD, study supports new low-cost, low-barrier, and uniform evidence-based associate professor and director of clinical trials in the Department of methods of alcohol-use prevention, compared to potentially stigmatizing, Dermatology and associate professor of clinical and translational science. highly variable, and costly in-person interventions. “Text messaging for alcohol use prevention is just one example of how public health providers can leverage technology to help people in ways we were not able to before,” Suffoletto said. STEM CELLS

NOV 2015 \ VOL 34 \ ISSUE 3 ARSENIC IMPAIRS STEM CELLS, AFFECTING MUSCLE MENOPAUSE REGENERATION AND HEALING JAN 2016 \ VOL 23 \ ISSUE 1 FREQUENT NIGHTTIME HOT FLASHES DURING MENOPAUSE Chronic arsenic exposure can cause stem cell dysfunction, leading to MAY BE LINKED TO MARKERS OF CEREBROVASCULAR DISEASE impaired muscle healing and regeneration, Pitt researchers found. More than 4 million Americans chronically ingest arsenic in their drinking water, as arsenic is one of the most abundant metals in the earth’s crust. “Whereas Most menopausal women experience hot flashes, a number of which previous research has examined the impact of arsenic and other envi- occur during sleep. Hot flashes are traditionally believed to affect quality ronmental contaminants on stem cell function critical for fetal and child of life for women but to have few health implications. Pitt researchers have development, there is very little information about how such exposures may explored hot flashes and links to heart disease, and, in a new study, they affect stem cells and their function in adulthood,” said senior investigator investigated a possible connection between hot flashes and brain health. Fabrisia Ambrosio, PhD, MPT, associate professor of physical medicine The investigators recorded the frequency of hot flashes using biological hot and rehabilitation. In the study, mice drank water containing 10 times the flash monitors in 20 women. They also used MRI brain imaging to detect federally safe arsenic level for humans, concentra­tions commonly encoun- white matter hyper­intensities, markers of potential disease in the brain’s tered by more than 140 million individuals world­wide. After five weeks of small blood vessels. The device recorded eight hot flashes per day on exposure, mice were subjected to muscle injury. Compared to mice given average. The women who had more hot flashes during sleep also showed clean drinking water, the exposed mice had significantly decreased ability more white matter hyperintensities on brain scans. Such women could be at to regenerate and recover strength after injury. Arsenic-exposed mice also higher risk for cerebrovascular disease. “Other factors, like age and cardio­ showed structural deficits throughout their muscle tissue’s extracellular vascular risk factors, did not explain this effect, so these findings suggest matrix. Researchers learned that arsenic caused heightened biochemical there is a relationship between menopausal hot flashes and blood vessel signals from protein complex NF-kB, which relates to matrix remodeling changes in the brain,” said principal investigator Rebecca Thurston, PhD, and tissue repair. They also revealed that, after blocking activation of NF-kB, professor of psychiatry. “Further work is needed to understand whether the exposed mice recovered normally. The researchers believe it could be one causes the other, or if hot flashes are a signal of some other vascular important to pay greater attention to environmental factors when assessing process that affects brain health.” tissue recovery and hope to explore the possibility of reversing the impact of chronic arsenic exposure in humans.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 45 RESEARCH INVESTIGATIONS AND REVELATIONS

CELL CANCER RESEARCH

OCT 2015 \ VOL 163 \ ISSUE 2 DEC 2015 \ VOL 75 \ ISSUE 24 IMMUNOLOGICAL SCARRING’S LINK TO DISEASE, SHARING CANCER RESEARCH DATA BETWEEN HOSPITALS CHRONIC INFLAMMATION EXPLORED PROMOTES FASTER TRANSLATION, ADVANCEMENTS

Infections have been linked to causing inflammatory disorders, yet With the proliferation of personalized therapies and precision m­ edicine, researchers have not been able to clearly identify the mechanistic asso- hospitals and research centers need more sophisticated systems to share ciations between defined infectious agents and the onset of chronic disease. data and even tissue samples. Pitt investigators and other researchers It’s a compelling question, given the prevalence of inflammatory disorders developed a system known as the TIES Cancer Research Network (TCRN) like inflammatory bowel disease, psoriasis, asthma, and others affecting to facilitate data and biospecimen sharing amid a network of cancer barrier tissue. Timothy W. Hand, PhD, assistant professor of pediatrics research institutes in order to hasten translation of research develop- and of immunology, and investigators from other institutions explored how a ments into patient care. The federated network uses advanced text single acute infection can have dramatic and longstanding consequences for processing of medical reports to openly share information across the tissue-specific immunity. The research team exposed mice to ab ­ acterium, UPMC CancerCenter; the University of Pittsburgh Cancer Institute; Georgia Yersinia pseudotuberculosis, which causes gastrointestinal infection. After Cancer Center, Augusta University; Roswell Park Cancer Institute; and the pathogen had been cleared, “immuno­logical scarring” remained: the Abramson Cancer Center of the University of Pennsylvania, which all Microbiota-dependent inflammation in fat tissue, coupled with damage collaborated to develop TCRN. The system is a useful model for promoting to the lymphatic system, disrupted communication between the immune translational research, especially for rare diseases and behaviors, said system and the tissue. Homeostasis was compromised long-term, and lead researcher Rebecca S. Jacobson, MD, MS, professor of biomedical the microbiota also perpetuated immune dysfunction post-infection. The informatics and of clinical and translational science. “With the TCRN, we researchers believe the study could provide a framework to understand how can study rare diseases and rare behaviors of common diseases much previous infections can induce breakdown of tissue immune homeostasis more effectively. Investigators may not have enough cases at a single and contribute to disease and chronic inflammation later in life. institution to support a compelling study, but they can now aggregate and access data and biomaterials across multiple institutions.” Jacobson and colleagues previously developed the language processing system TIES (Text I­nformation Extraction System), from which TCRN developed. SCIENCE

NOV 2015 \ VOL 350 \ ISSUE 6261 CORTICOMOTONEURONAL CELLS MAY BE FUNCTIONALLY PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES TUNED TO GOVERN OPPOSING MUSCLE MOVEMENTS JAN 2016 \ VOL 113 \ ISSUE 1 AGING AFFECTS CIRCADIAN RHYTHM OF Even the simplest body movements are generated by complex patterns of GENES IN BRAIN CELLS muscle activity. A team of University of Pittsburgh Brain Institute (UPBI) researchers, including Peter L. Strick, PhD, Thomas Detre Professor of Neuroscience, Distinguished Professor and chair of neurobiology, Our 24-hour circadian rhythm cycle controls nearly all of our brain and professor of neurological surgery, and scientific director ofUPBI , explored physical processes, from sleep-wake times to metabolism and cognition. how the central nervous system creates these patterns of motor output. Certain genes within almost all cells govern daily activity processes, They recorded neuronal activity in the primary motor cortex as a monkey yet these genes have rarely been studied in the human brain, especially made 24 different movements. They studied the activity of a special set with regard to how aging affects them, said study author Colleen A. of cortical neurons that have direct connections with motoneurons that McClung, PhD, associate professor of psychiatry. Pitt investigators exam- control muscles. These neurons are termed corticomotoneuronal (CM) ined thousands of genes from nearly 150 human cadaver brains to reveal cells. Strick and his colleagues found that CM cells are “functionally tuned.” that the circadian rhythms of gene activity change with aging. Along Some CM cells are active when the muscle they control functions as an with investigators at the University of Toronto, the researchers looked at agonist (generated force), whereas other CM cells are active when the samples from persons aged under 40 and over 60 to explore the effects same muscle functions as an antagonist (braked movement). Different of normal aging on molecular rhythms in the prefrontal cortex, a region populations of CM cells govern the separate functional uses of a muscle. involved with learning, memory, and general cognitive performance. They These results, and the concept of functional tuning, provide new insight identified 235 core genes that make up the molecular clock and saw that into how the primary motor cortex generates the patterns of muscle activity younger people exhibited signs of daily rhythm in their genes but that older that are so critical for dexterous movement. people experienced loss of rhythm. They also found one set of genes that surprisingly gained rhythmicity in older individuals. The researchers hope the findings can ultimately help develop treatments for cognitive and sleep problems that occur with aging and plan to examine the workings of brain circadian-rhythm genes in lab and animal models.

46 JOURNAL OF PAIN AND SYMPTOM MANAGEMENT

JAN 2016 \ VOL 51 \ ISSUE 1 RACIALLY INFLUENCED NONVERBAL COMMUNICATION COULD AFFECT PATIENT DECISION-MAKING AND TRUST

A small Pitt trial revealed that physicians give less compassionate nonverbal cues when treating terminally ill black patients compared to white patients — the first study to critically examine such interactions in a pressured, end-of-life scenario. The study analyzed nonverbal cues such as eye contact, body positioning, and touch, said senior author Amber E. Barnato, MD, MPH, associate professor of medicine and of clinical and translational science. Thirty-three ­hospital-based emergency medicine physicians, hospitalists, and intensivists agreed to participate in a simu- lation involving white and black actors portraying dying cancer patients and their family members. The doctors were unaware of the trial’s intent. Upon evaluation, the physicians averaged 7 percent lower scores for their nonverbal interactions with the black patients than the white ones. Doctors were more likely to stand bedside and sympathetically touch a white patient, Barnato said, while actions such as remaining near the SCIENCE ADVANCES doorway and holding a binder in front of them could signal defensive or disengaged behavior. The study could help explain why black patients and MAR 2016 \ VOL 2 \ ISSUE 3 their families are far more likely to request extraordinary life-sustaining PLACENTA MODEL EFFECTIVE FOR measures and report discrimination and worse communication with TESTING INFECTIOUS AGENTS their physicians. “Body language is a significant tool in building trust — or mistrust,” Barnato said. “To help black patients and their families feel welcome and encouraged to be partners in medical decision-making, it is The placenta anchors the developing fetus in the uterus, ­nourishes critical that doctors be aware of their verbal and nonverbal communication it, and provides a barrier against infectious agents from the and unintentional biases.” mother — yet it is one of the least well-understood human organs. Researchers at Pitt and Magee-Womens Research Institute (MWRI) constructed a cell-based model of the human placenta to inves- tigate how pathogens that cause birth defects cross from mother to fetus. While researchers have studied placental cell lines and PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES human trophoblasts isolated from full-term placentas, they sought FEB 2016 \ VOL 113 \ ISSUE 6 to overcome some shortcomings of these placental models by culturing a human placental trophoblast cell line in a microgravity STRUCTURE OF PROTEIN CLUMPS CHARACTERISTIC OF bioreactor system to construct a new type of model. The tropho- HUNTINGTON’S DISEASE DEFINED blasts were spun in a vessel to reproduce shear stress and rotational forces that better replicate the maternal-fetal micro­environment. The gene associated with Huntington’s disease makes a mutated protein The resulting cells fused to form syncytiotrophoblasts, which that carries a repetitive sequence called polyglutamine. In Huntington’s resemble the outermost layer of cells of the villous structure of patients, the sequence is too long, yet it had been unclear how the mutation human placenta. The researchers then exposed the model to a causes the protein to clump and cause the disease. Researchers at Pitt’s virus and to three different strains of Toxoplasma gondii, a parasite School of Medicine showed that the proteins in such clumps have a distinc- found in cat feces that can cause fetal infection resulting in mis­ tive structure that could provide insight into the molecular mechanisms carriage or congenital disease or disability. The three-dimensional behind the neuro­degenerative disorder. “Despite decades of research, model successfully replicated the barrier properties of the actual the nature of the protein deposition has been unclear, which makes it placenta and resisted infection, revealing its ability to further test difficult to design drugs that affect the process,” said senior investigator various infectious agents like Zika virus to see if, and how, they Patrick C.A. van der Wel, PhD, assistant professor of structural biology. can penetrate the placenta. “With our new model in the research “Using advanced nuclear magnetic resonance spectroscopy, we were toolkit, we and other scientists hope to advance our knowledge able to provide an unprecedented view of the internal structure of the of the placenta, examine its function, and learn how it can prevent protein clumps that form in the disease, which we hope will one day lead most, but not all, maternal infections from causing problems for the to new therapies.” He added that Huntington’s is one of many incurable baby,” said corresponding author Carolyn Coyne, PhD, associate neurodegenerative diseases that exhibit protein depositions in the brain. professor of microbiology and molecular genetics and of obstetrics, So insights from this research could advance understanding of similar gynecology, and reproductive sciences. Contributors included Yoel diseases and the mechanisms behind protein aggregation. Sadovsky, MD, Distinguished Professor of Obstetrics, Gynecology, and Reproductive Sciences, Elsie Hilliard Hillman Professor of Women’s and Infants’ Health Research, and MWRI director.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 47 RESEARCH INVESTIGATIONS AND REVELATIONS

ALZHEIMER’S DISEASE AND ASSOCIATED DISORDERS

JUL 2016 \ VOL 30 \ ISSUE 3 AGE-RELATED COGNITIVE DECLINE COULD BE INFLUENCED BY CHRONIC VIRAL INFECTIONS

Certain chronic viral infections may add to cognitive deterioration in other- wise healthy older adults, researchers at Pitt and Johns Hopkins University found. Previous studies have suggested a link between decreased cognitive function and exposure to cytomegalovirus, herpes simplex viruses 1 and 2, or the protozoan Toxoplasma gondii. However, these studies have assessed people at a single point in time, whereas the Pitt study examined blood samples from more than 1,000 participants age 65 and older who were annually evaluated for five years during a previous study on cognitive change. “Our study is one of the few to assess viral exposure and cognitive functioning measures over a period of time in a group of older adults,” said lead investigator Vishwajit Nimgaonkar, MD, PhD, professor of psychiatry, School of Medicine, and of human genetics, Graduate School of Public Health. “It’s possible that these viruses, which can linger in the body one’s entire life after infection, are triggering some neuro­toxic effects.” IMMUNITY The researchers saw that the viral infections influenced different aspects of cognitive deterioration often seen as age-related decline, and they are JAN 2016 \ VOL 44 \ ISSUE 1 working to determine whether certain people could be predisposed to GERMINAL CENTER RESPONSE GOVERNS MEMORY B-CELL greater decline based on more fine-grained analyses of viral infections. AND PLASMA CELL DIFFERENTIATION

Understanding how memory B cells and long-lived plasma cells develop is crucial for advancing vaccine design and for under- JOURNAL OF CLINICAL ONCOLOGY standing autoimmunity and pathogen persistence. Researchers from Pitt, including Mark J. Shlomchik, MD, PhD, UPMC Professor APR 2016 \ VOL 34 \ ISSUE 11 and chair of immunology, and Florian J. Weisel, PhD, research SYMPTOMS OF DEPRESSION COULD SIGNIFY GREATER LIKELIHOOD assistant professor of immunology, and other institutions found OF POSTSURGICAL COMPLICATIONS, HOSPITAL READMISSION that, during a germinal center response, memory B cells form before long-lived plasma cells take shape. The germinal center Patients reporting significant symptoms of depression before certain response, which produces memory B cells and long-lived plasma complex cancer operations could be at increased risk for postoperative cells, follows the generation of short-lived plasmablasts, but the complications and unplanned hospital readmissions, University of Pitts- signals that cause the response to make memory cells or plasma burgh Cancer Institute (UPCI) researchers found. Their study looked at cells — two mutually exclusive alternatives — have remained a patients planning to receive hyperthermic intraperitoneal chemotherapy mystery. Using mouse models, the investigators were able to tag with cytoreductive surgery (HIPEC+CS), a complex procedure to remove long-lived B cells at the time of their generation during synchronized abdominal tumors. Researchers evaluated 98 patients for depressive germinal center response. This process allowed them to determine symptoms prior to HIPEC+CS and found that 28 percent exhibited clini- the timing of the cells’ origin. They learned that the germinal center cally significant symptoms of depression. Within 30 days of leaving the response experiences a temporal switch in its output as time hospital after surgery, 22 percent of these patients were readmitted to progresses, revealing that the reaction first focuses on memory the hospital, and 31 percent experienced a complication such as infection. and only later on plasma cells. The study also revealed that the The researchers statistically adjusted for effects of demographic and heterogeneity within the memory B-cell pool is reflected in their disease-specific risk factors to conclude that patients with significant temporal generation, and that early and late germinal center B cells depressive symptoms were more than five times more likely than non­ have unique transcription profiles. This finding will enable future depressed patients to have a complication or hospital readmission within work to determine how the germinal center changes its output 30 days of discharge. “Postoperative complications and readmissions can and function with time. be very stressful for cancer patients and their families, not to mention very costly,” said lead author Carissa Low, PhD, assistant professor of medicine and of psychology with UPCI’s Biobehavioral Oncology Program. “We don’t yet know the mechanisms responsible for these effects. In addition to psycho­logical sources of depressive symptoms, there is evidence that the cancer itself may release factors that trigger some types of depressive symptoms, such as fatigue.”

48 JOURNAL OF ALZHEIMER’S DISEASE IMMUNITY

MAR 2016 \ VOL 52 \ ISSUE 2 MAR 2016 \ VOL 44 \ ISSUE 3 PHYSICAL ACTIVITY AND HIGH CALORIC BURN BALANCE BETWEEN GUT BACTERIA AND IMMUNE CELLS MAY REDUCE ALZHEIMER’S RISK CAN INFLUENCE AUTOIMMUNE INFLAMMATION

More and more studies indicate that physical activity can help protect the Scientists have long investigated how bacteria and other microorganisms brain from cognitive decline. Yet people tend to be more sedentary in old shape immune system development in the intestine, and Pitt researchers age, when the risk for developing Alzheimer’s disease and other demen- recently explored how common gut bacteria are controlled by the intestinal tias increases, said James T. Becker, PhD, professor of psychiatry and of immune system. If this control is not maintained, over-activated immune neurology, School of Medicine, and of psychology, Dietrich School of Arts cells can trigger autoimmune inflammation and other complications. and Sciences, and investigator on a Pitt and University of California, Los The researchers looked at the interaction of segmented filamentous Angeles, study that looked at physical activity and Alzheimer’s disease. bacteria (SFB) and the number of T-helper (Th) immune cells that make The researchers found that physically active older persons have larger gray inter ­leukin-17 in the gut. The latter is a signaling molecule that promotes matter volume in areas of the brain associated with memory and cognition. inflammation and has been connected to autoimmune diseases, including They also found that people with Alzheimer’s disease or mild cognitive arthritis, multiple sclerosis, and inflammatory bowel disease. Although it impairment who demonstrated high levels of exercise-associated calorie was previously known that SFB induces Th17 cells in the gut, disruption burn showed less gray matter volume reduction over time. The research of these cells’ function (by deleting the IL-17 receptor in gut epithelium) team examined data collected over five years from 876 people age 65 resulted in more SFB colonization. The absence of IL-17 signaling in the and older who received brain scans and periodic cognitive assessments. gut led to increased severity of autoimmune inflammation in a murine Participants also shared how often they walked, played tennis, golfed, model of multiple sclerosis. “Our study demonstrated these Th17 cells, in danced, or engaged in other physical activities to assess their caloric turn, control the gut’s SFB burden, and disruptions in the balance between expenditure per week. Using mathematical modeling, the researchers them can have important consequences,” said Jay Kolls, MD, Richard determined that participants who burned the most calories had larger King Mellon Foundation Professor of Pediatric Research and professor of gray matter volumes in the frontal, temporal, and parietal lobes of the pediatrics and of clinical and translational science. “These findings could brain, which are connected with memory, learning, and performance of have a tremendous impact on our understanding of how intestinal and complex cognitive tasks. Participants at the Pitt site with the highest energy autoimmune disorders develop.” expenditure showed larger gray matter volumes on initial brain scans, and larger volumes in these regions significantly reduced the likelihood of developing Alzheimer’s disease five years later. “Our current treatments for dementia are limited in their effectiveness, so developing approaches JOURNAL OF CLINICAL INVESTIGATION to prevent or slow these disorders is crucial,” said Becker. JUL 2015 \ VOL 125 \ ISSUE 7 STEM CELL GRAFTS WITH DEPLETED NAÏVE T CELLS CAN IMPROVE LEUKEMIA PATIENT OUTCOMES JOURNAL OF NEUROSCIENCE

OCT 2015 \ VOL 35 \ ISSUE 42 Graft-versus-host disease (GVHD) is a frequent cause of morbidity and INHIBITORY GRANULE CELLS SHED NEW LIGHT death following allogeneic hematopoietic stem cell transplantation (HCT). ON OLFACTORY BULB FUNCTION Warren D. Shlomchik, MD, visiting professor of medicine and of immu- nology, demonstrated in mice that naïve T cells cause more severe GVHD than memory T cells. Shlomchik explored whether depleting naïve T cells Pitt scientists are working to unravel the mechanisms behind the sense of from human transplanted peripheral blood stem cell grafts would reduce smell in mammals by focusing on the role of a specific type of inhibitory GVHD and lead to better outcomes following stem cell transplantation. In neuron known as granule cells. These inhibitory granule cells directly influ- the study, 35 patients with high-risk leukemia received allogeneic blood ence odor-evoked principal neuron activity in the olfactory bulb. However, stem cell grafts from which naïve T cells were depleted. The research it’s not well-known how sensory input recruits granule cells in olfaction. team — which included collaborators at the Fred Hutchinson Cancer The researchers, including Nathan Urban, PhD, professor of neurobiology, Research Center — also explored donor cell engraftment, acute and chronic investigated the synaptic basis of granule cell recruitment by using whole- GVHD, and immune reconstitution. All recipients of the naïve T cell-­ cell patch-clamp electrophysiology in acute mouse olfactory bulb samples. depleted transplants properly engrafted. While the incidence of acute They showed that sensory input to the olfactory bulb induces a barrage of GVHD was not reduced, the GVHD patients all responded to corticosteroids asynchronous synaptic excitation and highly reliable, short-latency synaptic without second-line agents. Additionally, chronic GVHD was dramatically inhibition onto granule cells via a disynaptic feedforward inhibitory circuit reduced, occurring in only 9 percent of cases, compared to approximately involving deep short-axon cells. The researchers successfully identified 50 percent following T cell-replete grafts that did not have naïve T cells feedforward inhibition onto granule cells as a core feature of olfactory bulb removed. The tested stem cell transplantation method also preserved the circuitry and established asynchronous excitation and feedforward inhibi- transfer of functional T cell memory. tion as critical regulators of granule activity. The results help scientists to understand how changes in synaptic input can significantly alter patterns of neural activity that drive olfactory-guided behavior.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 49 RESEARCH INVESTIGATIONS AND REVELATIONS

JOURNAL OF CLINICAL INVESTIGATION PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES AUG 2015 \ VOL 125 \ ISSUE 8 COMMON UTERINE TUMORS RESULT FROM MUTATION APR 2016 \ VOL 113 \ ISSUE 19 AND GENOMIC INSTABILITY EXPOSURE TO BLUE LIGHT REDUCES INFLAMMATION AND ORGAN DAMAGE IN POST-SURGERY MICE

Uterine leiomyomas are benign tumors arising from smooth muscle cells of the uterus. They are clinically diagnosed in 25 percent of women of repro- There’s long been evidence suggesting that light and ductive age and can cause bleeding, pain, and, in some women, infertility and ­circadian rhythms greatly influence our biology and physio­ miscarriages. They’re also the single largest cause of hysterectomy. Genomic logical responses to stress, said senior author Matthew R. sequencing showed that nucleotide variants in a gene called MED12 are Rosengart, MD, MPH, associate professor of surgery and associated with uterine leiomyomas, but their genetic influence and role in of critical care medicine. Pitt researchers explored this genomic instability are not well-understood. Researchers from Pitt’s School concept by exposing mice to either high-intensity blue, high-­ of Medicine and Magee-Womens Research Institute, including Aleksandar intensity red, or standard ambient white fluorescent light Rajkovic, MD, PhD, Marcus Allen Hogge Professor of Reproductive Genetics, for 24 hours before they underwent kidney or liver surgery Department of Obstetrics, Gynecology, and Reproductive Sciences, created that involved periods of blood restriction and restoration. a mouse model that expressed the most common MED12 variant and showed The high-intensity blue light revealed significant reductions that it stimulated uterine leiomyoma formation in both regular mice and in inflammation and organ-damage compared to the other in those harboring a uterine mesenchymal cell-specificMED 12 deletion. lights, the study found. The blue light exposure reduced Compared with regular mice, expression of the gene variant in MED12 the influx of neutrophils, a type of white blood cell related knockout mice resulted in earlier onset and larger leiomyoma lesions. The to inflammation, which can lead to organ damage. It also study concluded that this common human leiomyoma-as­ sociated MED12 inhibited dying cells from releasing the protein HMGB1, gene variant can cause leiomyomas and genomic instability in mice, which which triggers organ-damaging inflammation. Because is often observed in human leiomyomas. blind mice did not share similar results, the research team concluded that an optic pathway interprets the light, as opposed to the skin or another mechanism. The team also found that the blue light’s influence didn’t result from any

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES related disruption of sleep, activity, or circadian rhythms. Still, results of the study cannot be extended to humans,

MAY 2016 \ VOL 113 \ ISSUE 21 Rosengart says, without clinical trials. “While we were PHYSICS PRINCIPLE FURTHER EXPLAINS THE WORKINGS expecting to find some correlation with light spectrum and OF OUR SENSE OF SMELL the immune response, we were not expecting results quite so striking,” he said.

Researchers from Pitt and other institutions have found that the mechanism underlying our sense of smell follows a simple physics principle known as cooperativity. After odor molecules bind to specialized receptors located on millions of olfactory neurons, the receptors send signals from the neurons to the brain, where the scent is interpreted. While individual neurons have only one type of receptor, hundreds of different types of olfactory receptors are found, or expressed, in approximately equal numbers across the entire population of neurons, said senior investigator Jianhua Xing, PhD, associate professor of computational and systems biology. This diversity permits detection of a wide variety of smells. “Neuroscientists have been trying to uncover how nature accomplishes these two goals: selecting one, and only one, type of olfactory receptor for each neuron, while at the same time ensuring that all receptor types are represented in the whole population of neurons,” Xing said. The researchers used existing experimental data to create a computational model to show how olfactory receptor expression can be uniform across a single neuron yet diverse across the full population of neurons. They confirmed their model’s accuracy by correctly predicting findings from other research groups. The model exhibited a three-pronged regulation of olfactory receptor gene expression that conforms to the physics principle called cooperativity, which describes how elements of a system influence the behavior of each other rather than operate independently.

50 JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

FEB 2016 \ VOL 315 \ ISSUE 8 RESEARCHERS UPDATE SEPSIS, SEPTIC SHOCK DEFINITIONS AND TREATMENTS

Two years ago, the leading professional societies for critical care medicine appointed 19 critical care, surgical, infectious disease, and other doctors to revise the definitions of sepsis and septic shock to reflect advancements made in the pathophysiology, management, and epidemiology of sepsis. The new definition and updated treatment information were published through a series of Journal of the American Medical Association articles. The task force, which included Derek Angus, MD, MPH, Distinguished Professor and Mitchell P. Fink Professor and chair of critical care medicine, and Christopher W. Seymour, MD, MSc, assistant professor of critical care medicine and of emergency medicine, describes sepsis as a syndrome rather than a disease and calls for attention to early-stage sepsis symptoms like altered mental status, low blood pressure, and fast respiratory rate. Sepsis occurs when the body damages its tissues and organs in response to an infection, even a minor one. It is the number-one killer of hospital patients, yet does not exhibit identifiable biomarkers. The refined definition describes sepsis as a life-threatening organ dysfunction due to dysregulated immune system response to infection. Septic shock is now described as a subset of sepsis characterized by substantial and more deadly circulatory, cellular, and metabolic abnormalities.

JAMA CARDIOLOGY

JUL 2016 \ VOL 1 \ ISSUE 4 BLACKS WITH ATRIAL FIBRILLATION HAVE HIGHER RISK OF STROKE, HEART CONDITIONS COMPARED TO WHITES

Atrial fibrillation (AF) is the most common heart rhythm problem in the United States, affecting around 1 percent of the adult population and more than 5 percent of those 65 and older. AF is strongly associated with higher risk of stroke, heart failure, and mortality. According to research from Pitt’s School of Medicine, blacks with AF have nearly double the risk of stroke, heart failure, coronary heart disease, and mortality compared to their white counter ­parts. Researchers analyzed data from the Atherosclerosis Risk in Communities (ARIC) Study, which recruited more than 15,000 men and women from four states to investigate causes and track atherosclerosis and cardiovascular disease for more than 20 years. “We knew blacks were likely to have an increased risk of stroke, but the findings for heart failure, coronary heart disease (CHD), and mortality are novel and important,” said lead researcher Jared W. Magnani, MD, MSc, visiting associate professor of medicine. At the 20-year follow-up, incidence of stroke in black participants who developed AF was 21.4 per 1,000 person-years compared to 10.2 in whites. Rates of heart failure, CHD, and mortality were nearly double in blacks compared to whites. The researchers noted limitations to generalizability that included the geographic and biracial composition of the study.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 51 RESEARCH INVESTIGATIONS AND REVELATIONS

JAMA ONCOLOGY

AUG 2016 \ VOL 2 \ ISSUE 8 COMMON THYROID TUMOR RECLASSIFIED AS A NON-CANCER AFTER EXPERT REVIEW

Overdiagnosis surrounding thyroid cancer has been on the rise and can lead to costly, unnecessary treatment. However, some thyroid tumors are indolent, or nonprogressing, despite the presence of cellular abnor- malities that are usually deemed cancerous, said senior investigator Yuri E. Nikiforov, MD, PhD, professor of pathology and director of Pitt’s Division of Molecular and Genomic Pathology. Pitt researchers have used ThyroSeq v2.1, a next-generation sequencing test developed by Nikiforov and colleagues, to examine potentially cancerous cells. Recently, however, they explored reassessing the classification of a thyroid cancer. Incidence of a thyroid tumor known as encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) has doubled or tripled in the past 20–30 years and represents 10–20 percent of all thyroid cancer diagnoses in Europe and North America. Studies have shown that EFVPTC is not dangerous, yet it’s typically treated as aggressively as other thyroid cancers. Per recom- SCIENCE TRANSLATIONAL MEDICINE mendation from the National Cancer Institute, an international panel of pathologists and clinicians led by Pitt researchers reclassifiedEFVPTC as a JUN 2016 \ VOL 8 \ ISSUE 342 non-cancer to indicate that it’s noninvasive and has low recurrence risk, a KEY PARKINSON’S DISEASE PROTEIN’S TOXICITY move that should reduce the medical and psychological consequences of DUE TO MITOCHONDRIAL DISRUPTION receiving a cancer diagnosis. The pathologist panel, composed of experts from seven countries, examined 268 tumor samples to analyze cellular About 1 million Americans are affected by Parkinson’s disease features, tumor invasion, and other factors. “To my knowledge, this is (PD), characterized by tremors, slowness, balance difficulties, and the first time in the modern era a type of cancer is being reclassified as a abnormal gait. To slow or halt the disease, researchers need to non-cancer. I hope that it will set an example for other expert groups to understand what causes the degeneration and loss of neurons in the address nomenclature of various cancer types that have indolent behavior brain that govern movement and coordination. The protein alpha-­ to prevent inappropriate and costly treatment,” Nikiforov said. synuclein is a key component of Lewy bodies — the pathological hallmark of Parkinson’s — and Pitt researchers recently discovered that the protein disrupts mitochondrial activity, triggering toxicity. Lead investigator J. Timothy Greenamyre, MD, PhD, Love Family MSPHERE Professor of Neurology and professor of clinical and translational science, and colleagues used well-established rodent models to MAY 2016 \ VOL 1 \ ISSUE 3 show that the alpha-synuclein protein attaches to a mitochondrial eCAPS DEMONSTRATE TREATMENT POTENTIAL protein called TOM20 and prevents the mitochondria from prop- FOR RESPIRATORY CO-INFECTION erly functioning. The mitochondria, which generate power for the cell, operated suboptimally­­ , producing less energy and creating A new drug therapy developed by Pitt’s Center for Vaccine Research (CVR) excess cellular waste, which ultimately leads to neurodegeneration. targets bacterial biofilms and has proven to be effective against a deadly “The effects of alpha-synuclein on mitochondria are like making a respiratory virus, demonstrating an unprecedented ability to fight bacteria perfectly good coal-fueled power plant extremely inefficient, so it and a virus during a co-infection, said senior author Jennifer M. Bomberger, not only fails to make enough electricity but also creates too much PhD, assistant professor of microbiology­ and molecular genetics. The toxic pollution,” said Greenamyre. The team also explored methods research could advance treatments for drug-resistant bacteria, including to prevent alpha-synuclein’s toxicity. They employed gene therapy “superbugs,” which continue to proliferate alarmingly and remain resistant that forced the neurons to make more TOM20 protein, thereby to nearly all antibiotics. Chronic infections often resist the body’s efforts to protecting them from alpha-synuclein. An additional protein proved clear them from the lungs, sinuses, or other areas and lead to formation of able to prevent alpha-synuclein from sticking to TOM20, blocking biofilms, which are communities of surface-associated bacteria that can be harm to the mitochondria. The researchers are optimistic that these 400 times as resistant to antibiotics as a single bacterium. The researchers two nascent therapeutic methods can be tested in clinical trials. used an engineered cationic antimicrobial peptide, or eCAP, which has a structure similar to natural antimicrobial peptides, to rupture and destroy bacteria and viruses. The team grew biofilms of drug-resistantPseudomonas aeruginosa bacteria on airway-lining cells and then administered an eCAP.

52 The eCAP was 50 times more effective at fighting the biofilm than natural antimicrobial peptides and did not harm airway cells. When tested on airway cells infected only with respiratory syncytial virus (RSV), the eCAP reduced the number of viable virus particles by more than 150-fold. On cells subjected to RSV coupled with biofilm formation (the two frequently coincide in patients), the eCAP was 10 times more effective at fighting the biofilm in the co-infection state than traditional therapy. “Again and again, eCAPs are performing well in laboratory tests and mouse models. They’re an exciting possibility to help solve the antimicrobial-resistant superbug crisis that our world increasingly faces,” said coauthor Ronald C. Montelaro, PhD, emeritus professor of microbiology and molecular genetics, School of Medicine, and of infectious diseases and microbiology, Graduate School of Public Health.

JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

MAY 2016 \ VOL 315 \ ISSUE 19 FAMILY AND FRIENDS OF CRITICALLY ILL PATIENTS ARE OFTEN MORE OPTIMISTIC OF PATIENT OUTCOMES THAN DOCTORS PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES

When family and friends make decisions for critically ill patients, Pitt MAR 2016 \ VOL 113 \ ISSUE 11 researchers found that most of them harbor different beliefs about patients’ CAPSAICIN INHIBITS SENSORY NEURONS LINKED survival likeli­hood than doctors did. Decision makers were typically more TO PANCREATIC CANCER optimistic about a patient’s prognosis than doctors in a 2005 and 2009 survey of 229 surrogate decision makers who were family members or friends of intensive care patients at the University of California, San The destruction of certain sensory neurons could prevent onset of ­Francisco Medical Center. The survey asked both surrogates and doctors the most common and lethal form of pancreatic cancer, according to to estimate the likelihood that the patient would survive the hospitalization new research from Pitt and other institutions. Sensory neurons play from 0 (no chance of survival) to 100 (definite survival). In 53 percent of a significant role in pancreatitis, or inflammation of the pancreas, cases, the answers differed by more than 20 percent between surrogates which is a pancreatic cancer risk factor. The researchers believe and doctors, with doctors being less optimistic of the patient’s prognosis that sensory neurons may harbor key proinflammatory inputs that yet ultimately far more accurate. Participants were then asked to guess can lead to early stages of pancreatic ductal adenocarcinoma. the doctor’s patient survival estimate. Generally, they guessed somewhere The team injected capsaicin, the active agent in chili peppers, into between their estimate and the doctor’s actual estimate, indicating that newborn mice that had the most common genetic defects found they under­stood they were being more optimistic in spite of what they heard in humans with pancreatic cancer. Whereas these at-risk mice from the physician. Surrogates commonly explained that maintaining hope typically develop pancreatic cancer within six months, the capsaicin spurred the belief that the patient would do better than expected or that repressed sensory neurons that communicate with the pancreas. the patient had strengths unbeknown to the doctor, as well as support from The mice injected with the chemical that experienced the most religious beliefs. “It isn’t a bad thing for a patient’s family and friends to sensory neuron loss were cancer free after 18 months, the study’s have hope that they will recover,” said lead author Douglas B. White, MD, end. More than 90 percent of those that received no capsaicin died MAS, UPMC Professor of Ethics in Critical Care Medicine and professor of within six months. Capsaicin reduced inflammation and neuronal critical care medicine and of clinical and translational science. “However, damage to the peripheral and central nervous system and helped it is problematic when those overly optimistic expectations result in more to stop pancreatic cells from invading the spinal cord through invasive treatments in dying patients and delayed integration of palliative sensory neurons. By preventing migration of pancreatic cells, care that can alleviate suffering.” cancer development slowed or was prevented, said study leader Brian M. Davis, PhD, professor of neurobiology and of medicine.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 53 RESEARCH INVESTIGATIONS AND REVELATIONS

CANCER PREVENTION RESEARCH NATURE STRUCTURAL AND MOLECULAR BIOLOGY

JUL 2016 \ VOL 9 \ ISSUE 7 JUN 2016 \ VOL 23 \ ISSUE 6 BROCCOLI SPROUT EXTRACT PROTECTS AGAINST ORAL CANCER RESEARCHERS ELUCIDATE STRUCTURAL COMPONENTS AND MAY IMPEDE CANCER RECURRENCE OF HERPESVIRUS CAPSID

Cruciferous vegetables like broccoli, cabbage, and garden cress have a high Cryo-electron microscopy (cryo-EM) provides the necessary resolution concentration of sulforaphane, a potent compound that has been shown and maintains the natural environment needed to study the mechanisms to protect against carcinogens. University of Pittsburgh Cancer Institute and interactions that govern the assembly and function of functional researchers demonstrated that sulforaphane protected laboratory mice complexes like the protein shell of a virus. Pitt researchers, including against oral cancer — an unprecedented finding. Moreover, a low-cost, James F. Conway, PhD, associate professor of structural biology, employed easily distributed broccoli sprout extract that harnesses sulforaphane was cryo-EM to study the herpesvirus capsid, a complex protein assembly that shown to activate the same “detoxification” gene in the mouths of human includes hundreds of copies of four major subunits and smaller collections volunteers and, thus, could prevent cancer recurrence in survivors of head of several essential minor proteins, which, combined, enable infectivity. The and neck cancer, the researchers believe. Lead author Julie E. Bauman, team solved two high-quality capsid structures, one from human herpes MD, MPH, associate professor of medicine, Yan Zang, PhD, a postdoctoral simplex virus type 1 and the other from animal pseudorabies virus. Based researcher, and colleagues treated human head and neck cancer cells, as on their observations, the researchers developed a model to illustrate well as healthy mouth cells, with sulforaphane in the lab. In both cell types, subunit and domain organization. They found extensive networks of subunit the levels of a protein that activates genes that promote detoxification of contacts that support capsid stability. The networks form a pathway, the carcinogens increased. In a small clinical trial, healthy volunteers drank researchers observed, that may indicate the completion of DNA packaging a broccoli sprout and fruit juice beverage for several days, activating the from the capsid interior to the outer surface, which would initiate a key same protective genetic pathway in their mouths that was activated in the part of the infection process called nuclear egress. The subunit domain’s lab. In a separate study, mice predisposed to head and neck cancer that variances in orientation and folding between capsids suggest that the received sulforaphane developed far fewer tumors than their untreated common elements have been altered to carry out specific functions. Better counterparts. “With head and neck cancer, we often clear patients of their understanding of the structure and function of these capsids could lead first cancer, only to see them develop a second cancer with deadly conse- to improved therapies and vaccines. quences,” said Bauman, who has now launched a clinical trial involving cancer patients cleared of head and neck cancer. These participants take capsules containing broccoli seed powder in hopes of warding off a second head and neck cancer occurrence. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES

FEB 2016 \ VOL 113 \ ISSUE 8 PITT RESEARCHERS SHED NEW LIGHT ON REGULATION OF IMMUNITY CELL SIGNALING PROCESSES BY ENDOCYTOSIS

FEB 2016 \ VOL 44 \ ISSUE 2 INTERLEUKIN-35 LIMITS ANTI-TUMOR IMMUNITY AND PROMOTES Endocytosis, or active transportation of molecules into cells, governs T-CELL DYSFUNCTION IN THE TUMOR MICROENVIRONMENT intracellular signaling. Exactly how the process regulates signaling is largely unknown, however. Researchers from Pitt’s Department of Cell Biology, including Alexander Sorkin, PhD, Richard Beatty Mellon Professor of One of the goals of immunotherapy is to inhibit regulatory T cells, known Physiology and chair of cell biology, use the Ras protein to study signaling. as “Tregs,” and enhance the capabilities of tumor-specific T cells without In this study, Ras, which is central to normal and oncogenic signaling, causing inflammation, autoimmune complications, or other adverse was labeled with a fluorescent protein via gene editing so that it could be outcomes. Although Tregs impede autoimmunity, they also restrain tracked in living cells stimulated with epidermal growth factor (EGF). The critical tumor-specific T-cell responses. While Treg depletion improves team observed that the activated EGF receptors are rapidly internalized tumor rejection, the resulting adverse autoimmune conditions highlight the deeper into the cell via endosomes. Ras, however, was not internalized need to restrict Treg-targeted therapies to the tumor micro­environment. and remained within the plasma membrane, which indicates that EGF Researchers at Pitt, including Dario A. Vignali, PhD, professor of immu- receptors signal mitogen-activated protein kinases — which help govern nology, and other institutions explored Interleukin-35 (IL-35), a Treg-­ cellular responses to stimuli and regulate cell functions — exclusively from secreted cytokine, and its ability to limit anti-tumor immunity by inhibiting the plasma membrane. Sorkin and colleagues believe this is the first time T-cell proliferation and function. The researchers manipulated IL-35 in scientists have reported examining the localization of endogenous Ras in mice by applying an IL-35-specific antibody or by inducing Treg-­restricted living cells stimulated with EGF. ­deletion of IL-35 production that resulted in limited tumor growth across various mouse models of human cancer. Limiting intratumoral IL-35 enhanced T-cell proliferation, effector function, antigen-specific responses, and long-term T-cell memory. Treg-derived IL-35 promoted the expression of multiple inhibitory receptors, further highlighting newfound roles for IL-35 in limiting anti-tumor immunity and contributing to T-cell dysfunction in the tumor micro­environment.

54 Article JOURNAL OF BIOLOGICAL CHEMISTRY

Crystal Structure of a Transcribing RNA PolymeraseMAY 2016 \ VOL 291 \ ISSUE 21 II Complex Reveals a Complete Transcription Bubble TWO CELLULAR PROCESSES GOVERN RAPID CELLULAR Graphical Abstract Authors RECYCLING OF RECEPTOR Christopher O. Barnes, Monica Calero, Indranil Malik, ..., Michael A. Trakselis, Craig D. Kaplan, Guillermo Calero G protein-coupled receptors are the most abundant cell surface trans­mem­ Correspondence [email protected] brane receptors that activate or repress intracellular signaling pathways in response to extracellular stimuli. Of these medically important receptors, In Brief Barnes et al. reveal the architecturethe of parathyroid Pol hormone receptor (PTHR) regulates calcium mineral-ion II bound to a nucleic acid scaffoldhomeostasis. (NAS), It is involved with maintaining steady concentrations of comprising both upstream and downstream DNA duplexes andcalcium and phosphate in extracellular fluids and with bone turnover and transcriptional forks. The co-crystalrepair, and it's a target for the treatment of osteoporosis. Researchers structure uncovers the large range of interactions between Pol II and thefrom NAS Pitt’s Laboratory for G Protein-Coupled Receptors Biology, including and possible mechanistic links betweenPeter A. Friedman, PhD, professor of pharmacology and chemical biology NAS binding and translocation. and of structural biology, and Jean-Pierre Vilardaga, PhD, professor of pharmacology and chemical biology, investigated molecular and cellular processes by which PTHR transmits parathyroid hormone (PTH) signals in Highlights Accession Numbers bone and kidney cells. Upon PTH stimulation, the PTHR moves into endo- d Co-crystal structure of Pol II in complex with a nucleic acid 5C4X somes, where it engages the retromer complex, which promotes recycling MOLECULARscaffold CELL (NAS) 5C4J 5C3E of receptors to the cell surface. Sorting nexin 27 (SNX27) was identified d Pol II interacts with upstream and downstream DNA duplexes 5C44 as a new PTHR binding partner in isolated endosomes. The rate of PTHR JUL 2015 \ VOL 59 \ ISSUE 2 5C4A d Pol II coordinates strand annealing and the nascent transcript recycling decreased following depletion of SNX27 or VPS35, a retromer PITT RESEARCHERSat the upstream REVEAL fork STRUCTURAL COMPOSITION subunit. Mutating the PDZ ligand of PTHR disabled the receptor’s interac- OF ENZYMEd Trigger AND loop/non-template RELATED NUCLEIC strand interactions ACID SCAFFOLD may contribute to NAS translocation tion with SNX27 but did not affect the rate of recycling. This suggests that PTHR may directly bind the retromer complex. Recycling independent of A full picture of the structural composition of RNA Polymerase SNX27 may involve the N-ethylmaleimide-sensitive factor, another protein II (Pol II) featuring a complete nucleic acid scaffold has not been that transfers vesicles from one cell compartment to another, to bind PDZ available to scientists. Recently, however, Pitt researchers reported and mutant PTHRs. The researchers concluded that PTHR undergoes Barnes et al., 2015, Molecular Cell 59, 258–269 rapid recycling through both mechanisms. Such findings shed new light and described theJuly 16,crystal 2015 ª2015 structures Elsevier Inc. of Pol II in complex with a http://dx.doi.org/10.1016/j.molcel.2015.06.034 complete nucleic acid scaffold that reveals the architecture of a on cellular pathways of receptor signaling that are needed to develop new Pol II transcribing complex. The research team, led by Guillermo therapies for bone and mineral diseases. Calero, MD, PhD, assistant professor of structural biology, School of Medicine, explored the mechanisms and shape of Pol II to reveal a complete transcription bubble. While exploring the structure, they saw that an upstream duplex stretches over a wedge-shaped NATURE CHEMICAL BIOLOGY loop from the Rpb2 subunit, which comprises part of the struc- tural framework for DNA tracking during DNA elongation. By JUL 2015 \ VOL 11 \ ISSUE 7 revealing the structural composition, the researchers permitted NITRIC OXIDE AND NITRITE REACTIONS ARE KEY TO PHYSIOLOGICAL clearer visualization of the mechanisms and components of the FORMATION OF CELL SIGNALING MEDIATORS enzyme. At the upstream transcription bubble fork, rudder and fork loop 1 residues coordinate strand annealing and the nascent Nitric oxide induces a variety of signaling responses and chemical ­reactions RNA transcript. At the downstream fork, a network of Pol II inter­ under both physiological and metabolically-stressed conditions. Pitt actions with the non-template strand forms a rigid domain with the researchers, including Bruce A. Freeman, PhD, UPMC Irwin Fridovich trigger loop. The findings suggest that the varying open or closed Professor and chair of pharmacology and chemical biology; Francisco J. arrangement of the trigger loop may be linked to interactions with Schopfer, PhD, research associate professor of pharmacology and chemical the non-template strand and may be mechanically conducive to biology; and Dario Vitturi, PhD, research assistant professor of pharma- polymerase translocation. Ultimately, the cocrystal structure cology and chemical biology, identified new intermediates stemming from uncovers the large range of interactions between Pol II and the the reactions of nitrogen oxides that promote unique modes of cell and nucleic acid scaffold. tissue signaling regulation. One product, symmetrical dinitrogen trioxide (ONONO), promotes both fatty acid nitration and thiol S-nitrosation at neutral pH. Theoretical models had predicted physiological formation of this compound, and this mass spectrometry-based study demonstrated its generation in aqueous reaction systems, in cell models, and in vivo. Autox- idation of nitric oxide instigates the reaction cascade leading to ONONO formation, which occurs in the absence of metal centers. These findings have revealed new biochemical reactions regulating biomolecule function and signaling network activity that involve nitric oxide and nitrite-dependent nitrosation and nitration reactions.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 55

Pittsburgh is a city on the rise. As the city’s medical school, we seek to identify areas of need, contribute our expertise and energy, and strengthen partnerships to make a most livable city even better. COMMUNITY

Weaving a Safety Net

hen Elizabeth Miller, MD, PhD, arrived prevention and male athletes as leaders in their communities. at the University of Pittsburgh in 2011, The successful program is being used in many high schools in she hit the ground running. Chief of Southwestern Pennsylvania, and the Federation of Independent the Division of Adolescent and Young School Alumnae (FISA) Foundation and the United Way part- Adult Medicine and relentless advo- nered to support CBIM’s implementation in local high schools cate for children and adolescents, and colleges. The partnership also funded six domestic violence/ Miller immediately noticed that sexual assault agencies to provide training for area schools and ­Pittsburgh lacked a drop-in center for young people who do coaches, with a goal of training 2,000 coaches in the region. notW have stable housing and need a connection to community CBIM has gone international, with the program adapted for services, supportive adults, and food, or who need a little bit of cricket players in India. Miller says the focus for CBIM now is extra help with difficult life circumstances. She and community on the best strategies for dissemination and implementation partners quickly pooled resources to set up a youth center in the and doing smaller, more sociologic studies looking at the key Gay and Lesbian Community Center in downtown Pittsburgh. characteristics of coaches effectively implementing the program. While that center remains open, Miller’s vision for another What Miller calls her “dream project” is Manhood 2.0, which drop-in center recently came to fruition — because, as she says, she developed and is funded by the Centers for Disease Control “it’s important for marginalized youths to have multiple portals and Prevention (CDC). When CDC sent a call for proposals to through which to connect to support and services.” Funded by engage men and boys in sexual violence prevention, she looked the Allegheny County Department of Human Services and led at the gender violence prevention work being done and noticed by the Auberle Foundation with the support of multiple commu- they were mostly in school- or clinic-based settings. She saw a nity partners, including the Homeless Children’s Education need for community-based programming that includes in-depth Fund and Children’s Hospital of Pittsburgh of UPMC, 412 Youth discussion with young people over an extended period of time and Zone is a new, one-stop drop-in center to help young people live implemented by people with whom they have some level of trust independently. It has showers, child care, prevention education, or connection. In a partnership with Promundo, a global gender a reading room, and laundry. It houses trained staff members, violence prevention organization, the Urban League of Greater youth coaches, case managers, an on-site nurse, and a clinician from Miller’s division once a week. In addition to being professor of pediatrics, behavioral and community health sciences, and clinical and translational “ It’ s important for marginalized science and medical director of 412 Youth Zone and of other youths to have multiple portals community health services —like the Children’s Hospital of Pittsburgh of UPMC/Ronald McDonald Care Mobile, a mobile through which to connect to van that links medical services to communities with little support and services.” access to primary care — Miller is a tireless practitioner of community-engaged research. She is known for bringing to Pitt Coaching Boys into Men (CBIM), a prevention program that trains coaches to talk to their athletes about the importance of nonviolent behaviors toward women and girls, using the influ- ence of athletic coaches as powerful messengers for violence

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 57 COMMUNITY SUPPORTING OUR NEIGHBORS

58 412 YOUTH ZONE IS A NEW, ONE-STOP DROP-IN CENTER TO HELP YOUNG PEOPLE LIVE INDEPENDENTLY. IT HAS SHOWERS, CHILD CARE, PREVENTION EDUCATION, A READING ROOM, AND LAUNDRY. IT HOUSES TRAINED STAFF MEMBERS, YOUTH COACHES, CASE MANAGERS, AN ON-SITE NURSE, AND A CLINICIAN FROM MILLER’S DIVISION ONCE A WEEK.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 59 COMMUNITY THE PLACE WE CALL HOME

Pittsburgh, and the YMCA, Miller has implemented Manhood 2.0, engagement for the Clinical and Translational Science Insti- which mixes comprehensive sexuality and sexual violence educa- tute’s Com­munity PARTners Core and offering clinical care tion and information about consent/communication and healthy at the division’s transgender clinic and at Shuman Juvenile relationships with critical analysis of rigid masculinity norms. ­Detention Center. She is involved with 18 active grants, admin- It provides an 18-hour curriculum spread over six sessions and isters $2 million in federal funds, and launched one National run by trained facilitators in community settings. Young people Institutes of Health and two CDC-funded studies this year. How in local school districts can even participate in Manhood 2.0 as does she remain fueled for her many responsibilities? an alternative to out-of-school suspension. “Southwestern Pa. is an incredibly generous and compassion- “We have these amazing, intense, and wonderful conversations ate place,” says Miller. “It’s a critically important characteristic with young men about what it means to be a man, what they that makes me optimistic about our ability to make a difference envision for their futures, media messages, the harmful effects of for kids here. Building research-community partnerships and pornography, their experiences of racism and injustices, naming collaborations is so important in translating research into com- white privilege, and talking about male privilege,” says Miller. munity health impact. Collaboration has been really easy here. “You can see the gears working in their heads. It’s an immense When you meet with other people who care deeply about the amount of work and one of the most glorious, joyous projects.” health of children, youths, and families, and when you sit with Miller mixes her research-community partnership work that kind of energy, it just keeps you going.” with her other many roles, like being codirector of community

JOSH BADSTIBNER, 18, FROM DUQUESNE, GETS SOME LAP TIME WITH GIBSON, A 3-YEAR-OLD BEAGLE DURING A "NATIONAL PUPPY DAY" VISIT IN THE 412 YOUTH ZONE COMMON ROOM.

60 “By the end of the year, our goal for the trainees is for them to have or be close to having a grant ready for submission,” says Rubio. LEADS allows for some funding for trainees who want to disseminate their research at conferences or travel to receive specialized training. Mentoring the Transition PROMISED is a program with an innovative approach to mentoring, funded by the National Research Mentoring into Biomedical Research Network. Rubio says, “Because the biomedical research work- force does not reflect the diversity in the United States, there’s an effort to diversify the workforce. To do that, we need mentors who can specifically mentor people from diverse backgrounds. or postdoctoral fellows and junior faculty new to So, we developed PROMISED with the idea that mentors with the biomedical research workforce, navigating strong leadership skills would be more effective mentors.” the first few years of academia can be difficult. PROMISED provides online training modules that focus Securing research funding is essential, but what on leadership skills (including understanding academia and do you do if you have had very little preparation academic code, time management, executive shadowing, and in the nuts and bolts of being a researcher? Since managing others) and career coaching training. Rubio says that 2005, training successful clinical researchers in career coaching is about helping mentees take ownership of Pitt’s resource-rich environment has been the task of the University their careers and discerning for themselves, with some helpful Fof Pittsburgh’s Institute for Clinical Research Education (ICRE). guidance, what will help their career trajectories. Training programs are led by ICRE codirector Doris Rubio, PhD, Rubio will host about 100 people at Pitt in the upcoming who is also director of the center’s academic programs, director months to provide them with career coaching training. From of the Office of Evaluation and Office of Lifelong Learning, and that pool, 30 will participate in a one-year fellowship with director of the data center of the Center for Research on Health PROMISED. Care. In discussions with colleagues at five minority-serving “The energy and excitement about the two programs has institutions (MSIs — specifically Charles R. Drew University of been incredible,” Rubio says. “For both, I’d like to get to the point Medicine and Science, Howard University, Morehouse School where the programs are available on the Web, and people could of Medicine, University of Hawai‘i at M¯anoa, and University of reproduce them at their own institutions or go through the Puerto Rico), Rubio learned that these institutions sometimes programs independently. My goal is to disseminate them so they struggled to launch the research careers of their junior faculty. can have a much broader effect on the research workforce.” She also saw an opportunity to foster and develop Pitt’s strengths in scientific mentorship while being a good citizen. “Junior researchers at our partner MSIs have all had tradi- tional classes, like biostatistics and research methods,” says “We decided to provide some Rubio, professor of medicine, School of Medicine; professor nontraditional training like of biostatistics, Graduate School of Public Health; professor of nursing, School of Nursing; and professor of clinical and trans- how to write successful grants, lational science. “So we decided to provide some nontraditional how to publish papers, and training like how to write successful grants, how to publish papers, and training in biomedical writing.” training in biomedical writing.” Rubio received funding for two training programs — LEADS (Leading Emerging and Diverse Scientists to Success) and PROMISED (Professional Mentoring Skills Enhancing Diversity). Funded by the National Institute for General Medical Sciences, LEADS is a year-long program designed to meet the individual needs of trainees and junior faculty from participating MSIs who are underrepresented in the biomedical sciences and beginning their research careers. Once applicants are accepted into the program, they are assigned a career coach who helps the trainees identify which online modules they should complete (modules are readings, videos, research, and/or homework on different topics) and create a career plan for the year.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 61 COMMUNITY A HELPING HAND

THE MAIKURU PROGRAM, DEVELOPED BY JEANNETTE E. SOUTH-PAUL, MD, PAIRS TEEN MOTHERS WITH VOLUNTEER MENTORS—MAIKURUS—WHO OFFER SUPPORT, EXPERIENCE, AND A SYMPATHETIC EAR FOR THE NEW MOMS, WHO, LIKE NEW MOTHERS AT ANY AGE, HAVE A LOT OF QUESTIONS AND NEED REASSURANCE.

transportation costs, dinner, child care, a chance to socialize with their maikurus and other mothers, and a presentation. The presentations cover timely topics like child development, depression, contraception, goal setting, healthy relationships, A Wise Woman Teams intimate partner violence, self-concept and spirituality, stress, and maintaining a positive outlook. With Teens in Need “The rate of depression in teen mothers is twice as high as depression is in the rest of the teen population,” says Yassmin Al Aaraj, MD, MPH, project coordinator for the Department nexpected pregnancy can be a challenge of Family Medicine’s Maikuru Program, School of Medicine. for any woman, let alone a teenager. Teen “Depression is one of the problems that will prevent them from mothers have higher rates of depression, continuing their education, finding jobs, and establishing a have lower high school completion rates, family.” At the beginning and end of the program, South- are more likely to have a second unexpected Paul surveys the participants about issues like depression and pregnancy, and are more likely to have a baby ­problem-solving skills to measure whether the program is with low birth weight and slower cognitive beneficial (and she refers them to social services if necessary). development, according to the Centers for Disease Control and Follow-up interviews with participants who have completed UPrevention. Recognizing that teen mothers are in great need the program demonstrate its benefit. Teen moms who had been of guidance and support, Jeannette E. South-Paul, MD, UPMC through the program had a higher rate of completing high school Andrew W. Mathieson Professor and chair, Department of Family than teen moms nationally or in Pennsylvania. Al Aaraj says Medicine, began a mentoring program for these mothers called that teen moms and maikurus often want to keep meeting, so the Maikuru Program. the program offers a monthly continuation group meeting. “Maikuru” means “great aunt” or “wise woman of the village” Maikurus and their mentees often maintain their relationships in the Southern African Shona language. The Maikuru Program for years after participating in the program. pairs teen mothers with volunteer mentors — maikurus — who South-Paul began the program in 2009 and recently expanded offer support, experience, and a sympathetic ear for the new it to include a new program for mothers aged 19–25 and fathers moms, who, like new mothers at any age, have a lot of questions or current partners. Participants attend weekly sessions and and need reassurance. can be paired with a maikuru or a mentor couple. The program, funded initially by the Heinz Endowments “I just can’t begin to tell you how important it is for these and now by the Grable, Poise, and Fine Foundations, offers six teens to feel like they have social support and somebody that weekly meetings in Oakland, and participants are provided with can coach them in life,” says South-Paul.

62 Residency Combines Family Medicine and Psychiatry for Integrated Care

recent shift toward treating patients in integrated care settings bodes well for the School of Medicine’s combined family ­medicine–psychiatry residency program, which began in 2006 and is one of only five such programs in the coun- try. Based on the concept of one physician being able to treat a patient’s entire brain-body system, the program provides residents with full training in both family medi- cine and psychiatry, leading to dual board certification. Applications Ato the program have doubled in the past few years and are expected to increase by 50 percent next year, according to Michael Travis, MD, associate professor of psychiatry, School of Medicine, and director of residency training, Western P­ sychiatric Institute and Clinic of UPMC. 30 “This integrated care training model isn’t a fad,” says Travis. “We firmly believe that combined training is the training of the future because of all the current emphasis on patients being able to see one doctor and have that person coordinating as much of their care as possible.” Family medicine and psychiatry are a natural fit. Mental health is to 40 often entangled with physical health and vice versa, and primary care physicians are often the first health care providers to hear about any health issue. A physician trained to think about mental and physical health together can provide integrated care in one office visit. Travis says that 30–40 percent of the residents’ patients in their family health center clinics have a behavioral health diagnosis in addi- percent tion to whatever other comorbidities they have. “If people trust you as their primary care doctor, someone whom they might see regu- of the residents’ patients in their family larly, they’ll also trust you to care for their mental health,” says Travis. health center clinics have a behavioral health “Combined family medicine-psychiatrists may be primarily dealing with a patient’s diabetes, but that physician is also able to recognize and diagnosis in addition to whatever other treat the patient’s underlying anxiety and/or depression that’s making comorbidities they have. them feel even worse.” Trainees in the program can have rotations in areas like geriatrics, mental retardation services, eating disorders, community psychiatry, and forensics and can see patients at the Birmingham Free Clinic, run by Pitt’s Program for Health Care to Underserved Populations and the Salvation Army. Graduates of the program are finding increasing career opportunities and have gone on to employment with state hospitals, “ T his integrated care training integrated care settings, academic medical centers, and in research. model isn’t a fad. We firmly “Our trainees are seeing patients with extremely complex issues,” says Travis. “It’s exciting because they’re getting opportunities to be believe that combined training expert consultants for both family medicine and psychiatry categori- cal program colleagues. The trainees are family medicine physicians is the training of the future plus or psychiatrists plus. They’re going to be our future leaders and because of all the current ­educators in medicine.” emphasis on patients being able to see one doctor and have that person coordinating as much of their care as possible.”

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 63 COMMUNITY CLINICAL RESEARCH FOR HEALTHIER COMMUNITIES

A Milestone of Participation

itt’s Clinical and Translational Science Institute (CTSI) has reached a milestone: More than 103,000 people of all ages have signed up with its Research Participant Registry to learn about different health topics and/or participate in local health studies. The registry connects members of the community with investigators and studies that Paddress their interests or health needs. The registry launched in August 2008 with 18 partici- pants, as Kerri Jackson, administrator for CTSI’s registry, recalls. “We’ve worked hard to engage as many people as we can since then,” Jackson says. “Our online recruitment Remembering D. A. Henderson through MyUPMC, UPMC’s online patient management 1928–2016 system, has been incredible. Much of our enrollment can be attributed to word-of-mouth referrals and recruitment through UPMC and Children’s Hospital of Pittsburgh of eginning on August 19, 2016, news of the death of D.A. UPMC outpatient offices.” Henderson, MD, MPH, 21st Century Professor of Medicine and Public Health, quickly circled the globe, accompa- The feature that differentiates Pitt’s CTSI research nied by laudatory tales of his days with the World Health participant registry from other registries nationwide is Organization (WHO). It was a fitting tribute to the leader its focus on the participant. “We want to engage people for Bof the successful global campaign to rid the world of smallpox. the long term, give them a different avenue to obtain infor- Henderson, 87, died from complications following a hip fracture. mation about research, and show people how research Known to all as “D.A.,” he was born Donald Ainslee ­Henderson is relevant to their own health,” says Steven E. Reis, MD, in Lakewood, Ohio. He received a medical degree in 1954 from the University of Rochester, then joined what later became known associate vice chancellor for clinical research, professor as the Centers for Disease Control and Prevention (CDC). He of medicine and of emergency medicine, and director of earned an MPH at Johns Hopkins University in 1960 and was CTSI. “The registry also is a partnership with investiga- elevated to chief of the CDC’s virus surveillance section. In this tors to help them gain access to populations they might position, he came to the attention of the WHO and was tapped otherwise have trouble reaching and to diversify their to lead its worldwide smallpox eradication program in 1966. “The sense at the WHO was that this was an impossible participant base.” mission, so they chose a young man who didn’t have a repu­ To find new ways to engage current and new partici- tation to tarnish,” said Thomas V. Inglesby, MD, director of pants, CTSI’s registry has launched a new campaign called the UPMC Center for Health Security, where Henderson was Pitt+Me™ (researchrecruitment.pitt.edu/ctsi). Using a a resident scholar. strong digital messaging presence, the campaign hopes For 11 years, Henderson traveled between the WHO’s Geneva, to reach people wherever they are and whenever they Switzerland, headquarters and global smallpox hot spots. The $300 million surveillance and vaccination campaign achieved might be most interested in learning more about certain success, with the last naturally occurring case of smallpox health topics or ways to partner with research studies. isolated in Somalia in 1977. The disease was officially declared “We’re hoping to use social media to drive people to the eradicated in 1980. new website and, through a strong multimedia presenta- Henderson left the WHO in 1977 for Johns Hopkins, where he tion, engage them in the registry once they’re there,” says later founded a center for civilian biodefense studies. In 2003, Reis. “Using this approach is also getting investigators he joined the faculty of the University of Pittsburgh. H­ enderson served in the administrations of three presidents — George thinking about their studies in new ways. H.W. Bush, Bill Clinton, and George W. Bush — and received “Investigators who haven’t yet used the registry and many honors, including the National Medal of Science (1986) CTSI’s services should try them,” says Reis. “We all want and the Presidential Medal of Freedom, the nation’s highest to disseminate our research findings and see how our ­civilian honor, in 2002. work is benefiting people.”

64 DONORS

With grateful appreciation for their generosity, we acknowledge the following individual, corporate, and foundation donors whose contribu- tions of $500 or more to the University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, and Western Psychiatric Institute and Clinic of UPMC between July 1, 2014, and June 30, 2015, have supported us in our academic, research, and clinical missions. Thank you.

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 65 DONORS INDIVIDUAL

INDIVIDUALS Jack C. Bendheim Lawrence S. Busch Andrea Cole Renee J. Benson Sylvia Amdur Busis and Gail F. Combs and Joel Adelman William L. Benson Sidney N. Busis, MD William George Combs, MD *Vincent C. Albo, MD Steven G. Bentley, MD Lisa H. Butterfield, PhD William S. Conover II Suzanne R. Alexander and Albert M. Bernath Jr., MD Ann W. Cahouet and Thomas G. Cooney Sr. Frank V. Cahouet, Trustee *Neil H. Alexander, Esq. Ellie K. and Robert S. Bernstein Timothy E. Corcoran Joseph E. Calderone Jr., MD Gayle Martin and William C. Dominic N. Bertucci Vera Jane Cornes and Alexander Joseph Cambridge Cleon L. Cornes, MD Margaret J. Biddle Charitable Trust Nourah A. M. TH. and Mary E. and Carl L. Campbell Carolyn Corrigan Joan Bigley and Thomas G. Bigley, Ebraheem J. Alghanim Trustee Janet F. Cappy Mary M. Cosgrove Ali H. Al-Khafaji, MD Marcel Binstock, MD Carlos M. Cardoso Frances and Charles Cost Barbara A. and David W. Allen Denise Birsic and Daniel J. The Carenzo Family Gina Costello and John Milton Jane K. France and Christian Allison Birsic, Esq. Michael T. Carenzo Costello Jr., MD Rachel and Nduka M. Ruth E. Blake David K. Carpenter Dr. Patricia L. Krainz and Amankulor, MD Bruce M. Coull, MD Mrs. Donald Blechman *Margaret A. Carver, MD Cheryl and Bruce A. Americus Marion L. and William U. Couzens Nancy and William J. Blechman Margaretha L. Casselbrant, MD Patrice J. and Robert L. Americus Penny C. Covert and Leland S. Blough Sr., MD Darlene M. Cataldi and Joan G. Ammer, MD, and James P. Covert, Trustee Eva Tansky Blum, Esq., Trustee James F. Cataldi, DMD John L. Ammer, MD David F. Cox, MD Richard M. Boccabella Robert A. Caughey Jr. Maureen M. Anderson and Marjorie M. and William L. Cox Mary Ann and Chuck Bogosta George W. Causey Trust Eric N. Anderson, Esq. Donald J. Crammond Michael J. Bonidie, MD Gilbert B. Causey, MD Tori Anderson / Walk with Tori Laura Lynne Cregan and Cheuk K. Chan Frances A. Armitage and Katherine M. and Jeffrey W. Bost Kevin M. Cregan, MD Yvonne R. Chan, MD Charles S. Armitage Sr. Karen S. Boujoukos and Albert A. Crimaldi, MD, PhD Arthur J. Boujoukos, MD George Chao Robert M. Arnold, MD Jill Chipps and Herbert E. Croft, MD Richard A. Boulden Paul K. Chao Mary Ann Aronson Paul M. Cryder Professor Dana H. Bovbjerg Jane P. Charlesworth and Andrew Y. Ashikari, MD Joseph Curtin James N. Bower, MD Ernest E. Charlesworth, MD Anuradha Ashwat William M. Curtin, MD Barbara and Gary Bowser Barry M. Chauser, MD Stephen M. Atkinson Robert G. Cypher Geneva McKelvey and Alan Arthur Axelson, MD Susan and Michael Boyle Steven A. Chernus, MD Laila M. Darhouse-Ziady Thelma I. Badwey and Cammi Stohl and Lance Brady Shirley M. Chervenick and Randi and *L. Van V. Dauler Jr. Robert E. Badwey, MD Robert W. Bragdon, MD Paul A. Chervenick, MD Nilesh B. Dave, MD, and Ray Ballantine Dr. Rhonda Metter Brand and Richard A. Chesnik, Esq. Manisha Dave, MD Michele M. Bamburak Randall E. Brand, MD Dr. Kazuyuki Chibana Jamini Vincent Davies Richard N. Baney, MD William R. Brandon, MD Linda Z. and John F. Chizmar Malindi Davies and Raj Dhaka Wendy and David E. Barensfeld Barry David Brause, MD Alan David Christianson, MD Sarah Davies, MD, DDS, and Walter D. Barker Nancy B. Brent, MD, and Benjamin J. Davies, MD David A. Brent, MD Constance Ren-Tien Chu, MD Diane Dihtzeruk Barna Bridgett K. Davis, MD Gary R. Brickner, MD Richard Chu Richard B. Barnett Nancy N. Davison and Ann and Paul R. Bridges Roberta M. Churilla Lisa J. Barthelemy Thomas M. Davison, MD Loretta A. Brooks and Susan H. and Alan D. Citron Susan J. Bartlett and David L. Christina Decker Daniel H. Brooks, MD Tanyia H. Clagette and Bartlett, MD Nicholas J. DeIuliis David E. Brougher, MD Vaughn S. Clagette, MD Monette G. Basson, MD, and Geraldine W. Dellenback and Andrew J. Clark Geoffrey H. Basson, MD Jeffrey S. Brown, MD Dr. Robert J. Dellenback Linda W. and G. Reynolds Clark Brian Baturevich Betsy Levine-Brown and Marilyn D. and Armand C. Dellovade Marc L. Brown Courtney N. Clarke James E. Bauer, MD Amy March and Todd J. Derr Jill A. Brufsky, PharMD, and Gregory J. Clawson Julie E. Bauman, MD Alida C. DeRubertis and Adam Brufsky, MD, PhD Shelley Wyckoff Clement Marian C. Baur Frederick R. DeRubertis, MD Seth J. Brufsky Mary F. and Frank J. Clements James R. Baxter Tara and Ravi Desai Sylvia S. Bucci Jay W. Cleveland Jr. Christine C. Beard Kim and Stephen P. DeVecchis Terry L. Buckenheimer, DMD William H. Cleveland II, MD Dr. Barbara A. Dappert and Stephanie Buck Dewar, MD, and Diane C. Budd, RPh, and Michael J. Becich, MD, PhD Kelly B. Close, MD, and Eric Close James C. Dewar Jr., MD Robert Michael Budd, MD Dorothy B. Beckwith and G. David A. Clump II, MD Rita DiChiera Alan P. Burckin, MD Nicholas Beckwith III, Trustee Melissa Reimel Cognetti, MD, and John C. DiDonato John P. Burke Susan S. and David Becraft David Michael Cognetti, MD Andrea DiMarco Tracy Robin Seewald, MD, and Dennis J. Beer, MD Michele McKenney and Dennis M. Domsic Steven A. Burton, MD Charles C. Cohen Jean W. Donaldson Carrie H. and H. Adam Cohen Susan S. Dorrance and *Joni H. Cohen and Roy G. Dorrance III Jesse D. Cohen, MD Every effort has been made to ensure the accuracy of these records. Diemthuy Duc Bui, MD, and Any errors or omissions may be brought to the attention of the Nancy B. Gold-Cohen and Gerald Paul Douglas, PhD Steven H. Cohen University of Pittsburgh and UPMC Medical and Health Sciences Robert C. Douthitt Irrevocable Trust Dana Cohn and Foundation: 412-647-3379 or [email protected]. Warren Meisel Cohn, MD

66 *BEFORE AN INDIVIDUAL’S NAME INDICATES THE PERSON IS DECEASED L–R: BRUCE COULL, JOHN LOEB, AND IVAN SHULMAN

Class of 1972

fter the School of Medicine Class of 1972’s 40th reunion “Jack was the model for a clear-thinking, compassionate but in 2012, a few classmates met to continue reminiscing. scholarly approach to patients,” says John Loeb, MD, a rheuma­ In their discussions, they all realized that their time at tologist in private practice. “He gave brilliant talks; even if you’d the University of Pittsburgh had been such an influence been up all night, you tried to go to his rounds because he was such in their lives that they wanted to honor those years and a great bedside teacher. He was the teaching-clinician role model theA mentors they had enjoyed. That night, they made a decision that’s such a huge influence when you see patients yourself.” to organize members of the class to give a gift to the school. They To honor their mentors and the education they received at Pitt, continued planning in the weeks after in an informal group, the steering committee for the Class of 1972 decided to support which is currently composed of Richard B. Kasdan, MD, Leslie R. student education. The summer after their first year, medical Laufman, MD, Gregory McClure, MD, Ernest E. Moore, MD, Bruce students typically work on their Scholarly Project, a longitudinal Coull, MD, John Loeb, MD, and Ivan Shulman, MD, MM. research experience throughout the four years of medical school, Helping others was a core principle of the Class of 1972. “When and the Class of ’72 Research Fund helps offset expenses of one we started in 1968, our class had a sense of social activism — there selected student’s summertime research. were protests, the Vietnam War was going on — it was a difficult “The fund isn’t so much about turning med students into time politically and socially,” says Dr. Shulman, voluntary assistant academic researchers; it’s about showing that bench and clinical professor of surgery at the University of California, Los Angeles, research are important educational experiences for any doctor,” longtime general surgeon in the Los Angeles area, and professional says Dr. Loeb. “We see it as a vital part of medical education.” conductor and oboist. Many members of the class were greatly The School of Medicine made its first award for the summer of influenced by professors and mentors, including Ken Rogers, MD, 2016. The recipient, Sheri Shiyu Wang, a Pittsburgher and rising chair of what was then the Department of Community Medicine second-year medical student, conducted research in the Plastic at the School of Medicine. Dr. Rogers organized a rotation in the Surgery Adipose Stem Cell Research Laboratory. Ms. Wang juggled Navajo Nation in Arizona that influenced many class members. a few research projects in the summer of 2016, but her Scholarly “Ken saw the world from the downtrodden perspective,” says Project research involved isolating lymphatic endothelial cells from Dr. Shulman. “He saw medicine as a gift to give, and it fit well with the human adult dermis, examining the influence of mechanical our class’ social consciousness.” stress on these cells and how stretching them in vitro leads to Another memorable professor was Jack D. Myers, MD, chair different cell signaling and possibly to lymphedema. Ms. Wang, of Pitt’s Department of Medicine from 1950 until 1970. “He was who wants to pursue a career as a clinician-researcher in plastic a structured, almost militaristic kind of guy who had very high surgery, says of the award, “It has done wonders for me. Otherwise, standards, and you had to perform at a high level. You knew that I would’ve had to get a summer job on top of my lab work. I feel as you were doing well when he lit a cigar during rounds,” says if I did a lot of hard science, and I built my management skills.” Dr. Coull, William M. Feinberg, MD, Professor in Stroke Research, “All of us had a research project, and we all benefited from professor of neurology and of medicine, and vice dean for clinical it,” says Dr. Loeb. “We’re making a statement that we believe in affairs, University of Arizona School of Medicine. paying back and showing gratitude to the people and the place that educated us.”

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 67 DONORS INDIVIDUAL

Sara L. Downey and Fracasso Family Dr. Scott R. Gunn Dr. L. John Hoover James L. Downey, MD Lanie K. Francis, MD and Patrick H. Gurrentz Daniel C. Hostetler Thomas M. Dugan, MD Elie Francis, MD Rodger Gurrentz Linda K. Houy and Michael Terry L. Dunlap Richard D. Frank Beth R. Gusenoff, DPM, and Lucien Houy, DMD Leslie O. Dunn Gary W. Frazier Jeffrey A. Gusenoff, MD Ann Hubbert Mary Lou and Richard Durr Douglas A. Freeman Linda J. and Richard P. Gustafson *Maggi L. Hullett, MD, and Dr. Martha L. DuShaw and Henry Clay Frick Rodgers Trust Stephen R. Guy, MD Joel M. Hullett, MD Robert D. DuShaw Gary Jay Friedman Margaret C. Hagberg, MD, and Aura R. Hulme Patricia K. Eagon, PhD Friends of Mrs. Jane T. Frost William C. Hagberg, MD Ellen R. Hulnick and *Warren D. Hulnick, DDS Kimberley J. Eberlein and Hilda Pang Fu, MLS, MPM, and Lynn H. Hale and Wayne A. Hale, MD Timothy J. Eberlein, MD Freddie H. K. Fu, MD Anthony Halli Priya Humar and Abhinav Humar, MD Harvey Seymour Edber, MD Clyde E. Fuller Scott J. Hamill Sue Hunter Stephen D. Edelman Robert Scott Furman, MD Nancy Hamilton Edward W. Icardi Karen K. Egorin Jill Fusaro Renea L. Hammerman and Calvin T. Iida, MD Dr. David E. Eibling Annie Futrell and Samuel I. Hammerman, MD April F. Eichler, MD, MPH J. William Futrell, MD Abdulla Najimdeen Hamoodi Joe R. Irwin Peter G. Ellis, MD Alan L. Gabriel Barbara J. and Robert W. Hannan Mary Hennessey Iyer Jonathan Engh Mary Louise and Henry Gailliot Loretta L. and Thomas M. Hanwell *J. Fraser Jackson, MD Eric R. Erlbaum, MD Madeliene Elaine Gainers, MD Charles W. Harbaugh David Jacobs, MD Bob Errey Patrick A. Gallagher John L. Harrington, MD Ian Jacobs *Dorothy Erwin and Mark H. Erwin Angela M. Garcia, MD Betty L. Harris and Jean Lynn Jacobs and Samuel A. Jacobs, MD W. Craig Esterly Glenn D. Gardner, MD *Barry C. Harris, MD Beverly T. and Andrew J. Jarabak Sally A. Evans and J. Lynne Garrison, MD C. Scott Harrison, MD Joe N. Jarrett Jr., MD Terry L. Evans, MD Stephen Gaudet Heywood A. Haser, MD *Rosemarie C. Jew and Richard G. Evelyn Carolyn H. Geraci and Caryn Hasselbring, MD Edward W. Jew Jr., MD Grace M. Faber and Anthony R. Geraci, MD Paul Haurilesko Farris T. Johnson Jr., MD Christopher N. Faber, MD Paula and *Martin G. Giglio Stuart Hayim Richard H. Johnson Joseph Faber John R. Gilbertson II, MD Rick Heald Roy T. Johnson Gloria and Michael Fader William Northwood Gilleland Jr., MD Brockton J. Hefflin, MD Susan A. and William R. Johnson Renetta Fatula and Maryedna Gillespie-Gennaula Ruth Champlin Hefflin George M. Fatula, MD Bradford D. Johnston, MD Matthew R. Gingo Barbara A. Heigl Christine M. Fulton and Gerald S. Johnston, MD Tammy S. Shields and Dennis Heindl George A. Fechter Susan S. Johnston and Mark T. Gladwin, MD Gertrude E. Hellerman Karen Wolk Feinstein, PhD, and Michael V. Johnston, MD Megan and Robert I. Glimcher Charitable Trust Fund Steven F. Feinstein Marilyn S. Johnstone and Lee Glunt and J. Roger Glunt, Trustee *Theodore R. Helmbold, MD John H. Feist, MD Graham F. Johnstone, MD John J. Godleski, MD Sarah J. Heppenstall and Anita and Gerald E. Feldman Elaine V. Jones, PhD Sally Weigler Golden and C. Talbot Heppenstall Jr. *Albert B. Ferguson Jr., MD Estate of Laura C. Jones Thomas B. Golden Jr. Jose D. Herazo-Maya, MD Arlene Butera Ferrante Lisa Jones and Cynthia P. Goodman and Georgia C. Hernandez and Robert T. Jones Jr., MD Laura K. Ferris, MD, PhD, and Mark A. Goodman, MD Robert M. Hernandez, Trustee Robert L. Ferris, MD Kevin David Judy, MD Ellen R. Goodman Linda Hertzberg and Caryn Fine, MD Arthur Jurchisin Sandra Green and Lee S. Goodman Richard W. Hertzberg, PhD Dr. Judith Albert and Kamal K. Kalia, MD Estate of Margaret S. Gordon Rose M. Hertzog Anthony B. Fiorillo Harriet Kalin and Joshua Kalin, MD Patricia M. Gordon John B. Hibbs Jr., MD Sylvia F. Fischer Gayle Louise Tissue and Anne M. Gordon and Shari Hicks-Graham, MD Audrey Hillman Fisher and Yiannis Kaloyeropoulos Stanley L. Gordon, MD Richard Higger Timothy O. Fisher Carole and Daniel G. Kamin Franklyn R. and Dale E. Gorell Margaret M. Hill and James R. Fitterling Margaret M. Kanaan Irene W. and Thomas C. Graham John B. Hill, MD Meghan E. Fitzpatrick Irene Getzie Kane, PhD, and Elizabeth G. Graham and Mr. and Mrs. Thomas M. Hill Eleanor M. and Hugh J. Flanagan Kevin M. Kane, MD William L. Graham, MD William Talbott Hillman Kimberly T. Fleming and James D. Kang, MD Louis A. Grant Jr. Lauren Denny Hirsch Curtis D. Fleming Steven Enright Kann, MD Bonnie S. Green David R. Hirsh Lore M. Flickinger David N. Kaplan Laurence B. Green William A. Hite G. Elaine Flinn and Marsha B. and Robert Karp Richard A. Flinn, PhD Michelle N. Gregory Tuyet H. Hoang Richard B. Kasdan, MD Ellen and Robert Flug Charles J. Greyhosky David R. Hoch Jonathan Kass Edward L. Foley, MD Sara M. Bradley, MD, and Susan S. Hogarty Jeffrey R. Grieb Mary Lou Katz and David L. Katz, MD Lisabeth A. and Jeffrey Allen Ford Jeffery P. Hogg, MD Estate of Robert E. Grindle Amy M. and Dennis J. Kelleher Wendy B. and Stephen A. Fornoff Kathleen N. and Carl William Groppe Jr., MD Lawrence P. Holleran Charles F. Kelley Jr., MD Tracy L. and J. Clifford Forrest Janet M. Levin and Frank J. Gruber Catherine B. and Bruce E. Holman Daniel L. Kelly The Foster Charitable Trust Ina and Lawrence N. Gumberg Cathy and Sy M. Holzer, Trustee Richard Kelly Isabel and Lee Foster II Harvey E. Gumto Elmer J. Holzinger, MD Susan L. Kerr, MD James M. Fox, MD Leonard G. Kibert, MD, PhD

68 *BEFORE AN INDIVIDUAL’S NAME INDICATES THE PERSON IS DECEASED Jennifer A. Corbelli and Cynthia P. Liefeld, PhD, and Anne-Marie B. McCoy, MD, and Marie R. Baldisseri, MD, and Jeremy D. Kimmel, PhD Paul A. Liefeld, MD Matthew S. McCoy, MD Srinivas Murali, MD Dusty Elias Kirk Gregory L. Lignelli Katharine G. McCullough and The Anita Cecilia Murcko, MD Thomas J. Kirsch Carol and Mark Limbach Honorable Samuel A. McCullough Mary Murdy Edward M. Klaman Chih-Tsung Kang, PhD, and Sandra V. McCurdy Raghavan Murugan, MD Brooke N. Klatt and Brian A. Klatt, MD Li-Yin Lin, PhD Nancy A. McDonald Ruth N. Mussa Kathryn U. and Cary H. Klein Rick C.S. Lin, PhD Antoinette J. McGinley Patricia Randolph and Anne Marie Czyz-Klemens, DMD, R. C. Lin, MD, and Shiow-Bih Lin, MD Thomas J. McGrath Jr. Ernest M. Myers, MD and Lee James Klemens, MD Judith K. Linaburg and Carol Z. McGrevin, PhD, and Lou Rene Myers Nancy E. Davidson, MD, and Thomas Ronald G. Linaburg, DMD Gene R. McGrevin Marlee S. Myers, Esq., Trustee, W. Kensler, PhD Nancy Rozendal and Jo Ann Haller, Esq., and and James R. Myers Cheryl Lynn and Douglas E. Knoch Gordon Lisker Daniel C. McGrogan, Esq. Sandra P. Myers Samuel A. Kocoshis, MD Edward T. Liverani Martin G. McGuinn Barbara Deutsch Nadel and Beth Ann Hellerstedt, MD, and Penny Loeb, MD, and Christine L. McHenry, MD Alan Marc Nadel, MD Darren Kocs, MD John M. Loeb, MD Linda and David McKamish Marlene Naft Aaron R. Kolko Joan Harvey, MD, and Janet and Dennis McKamish Mary J. Nagel and Michael T. Lotze, MD Johann F. Kolling Thomas J. McKinney John Robert Nagel, MD Harriet Van Ingen Love and Susan P. Kondziolka and Melissa L. McLane, MD Joseph P. Nedresky, MD Howard M. Love Douglas S. Kondziolka, MD Julie S. McLaughlin and Martin Nesbitt Jane Vaughn Love Wayne K. Kong Mark R. McLaughlin, MD Barbara Netter Gary R. Luchini Kim and Don Kramer Deborah K. McMahon, MD Lila G. Nettrour and John Machota *David Kremen Kathleen K. McMillen and Lewis F. Nettrour, MD Kathryn L. Macielak and Nancy S. Krieger Robert E. McMillen, MD James Allan Newcomb, MD James R. Macielak, MD David A. Kristo, MD Stephen A. McNeely Patricia A. Newingham Doreen A. MacMillan *Al Kubany Kathleen W. and David McSorley Ann K. and William R. Newlin Victoria Madero-Arnold Lawrence M. Kulla, MD George E. Meanor John A. Nice Amy Malaney Nancy I. Kunz and Daniel A. Medalie, MD Theresa L. Nimick-Whiteside, PhD Anne M. Mallampalli and Heinz W. Kunz, PhD William J. Medica Robert M. Nishikawa Rama K. Mallampalli, MD James P. Kushner, MD Donna L. Medich and Marjorie J. Nord and William H. Mallinson Paula Marie Jernigan, MD, and George F. Medich, MD Roland E. Nord, MD Richard W. Maloney, MD Andrew David Laman, MD Anne R. Medsger and Harriet Sutton Norgren Amy and Gavin Mann Verna R. Laman and Thomas A. Medsger Jr., MD Margaret G. O’Daniel Richard M. Mann, MD David Laman, MD Allan H. Meltzer Wendy M. O’Donnell and Michele L. Dorfsman, MD, and Joseph Manzinger Jr. William Menzies, MD Christopher P. O’Donnell, PhD Phillip E. Lamberty, MD Vicki March, MD Richard B. Meredick Jr., MD Margaret H. and Jack Offenbach Howard Norman Lang, MD, and Janet R. Markel Arlene and Bob Merson *James F. O’Keefe Jr., MD Carol Eckstein Lang Alvin Markovitz, MD Maria T. Metro Lois A. Pounds Oliver, MD Margaret D. Larkins-Pettigrew, MD Nikol and Stanley Marks, MD Pamela A. Michaels Mark B. Orringer, MD Patricia A. Larson and Lucine O. Marous R. Michelson Thomas J. Osborn Christopher E. Larson, DMD, MD *Helen B. and *Curtis R. Marquard Philip J. Migliore, MD Sandy and Gene O’Sullivan Steffi Oesterreich, PhD, and Marian K. Marquis, MD, and Adrian V. Lee, PhD Katherina A. Miller Trust Charleen T. Chu, MD, PhD, and William Edward Marquis Tim D. Oury, MD, PhD Edward S. Lee, MD Cedric B. Miller, MD Sheldon Marstine Joyce A. Pacek and Joon Sup Lee, MD Darlene A. and Ronald J. Miller Josephine B. Martinez Robert Francis Pacek, MD Kathleen M. Lee and Thomas K. Miller, MD John Mary Mary Panitch and Robert E. Lee, MD Natalie D. Miltenberger Myrna and Mark Mason Howard Barry Panitch, MD Freya Elizabeth Hory Lee, PhD, Michael D. Minton, MD Carolyn C. Massaro and Clara A. Paschitti and William Lee, MD Bharat B. Mittal, MD, and *Joseph A. Massaro Jr. Mark E. Pasquerilla Susan Leff and Louis E. Leff, MD Raj Mittal, MD William E. Master, MD Stuart K. Patrick Anne Gendler and David Leib Lesley Moffett-Krause Patricia J. and Robert L. Mathay Kathleen and Demetrios Patrinos Alice Laffey Leone and Jane Moffitt Judith A. and James L. Matheny Jeannette E. South-Paul, MD, and Peter P. Leone Jr. Rudy L. Molnar Rachel J. Givelber, MD, and Michael D. Paul, MD Gaynell J. Lerew Ruth M. Montgomery Michael A. Mathier, MD Richard Paul, MD *David J. Levidow Jeffrey L. Moody Andrew M. McAlpin, MD Lynda and Kenneth Payne *Sally M. Levin Dawn A. and Richard F. Moody Clyde Edward McAuley, MD Margaret Mary Mateer and Sandra Levin Christine Moore Bruce A. McClane, PhD John R. Pearson Linda S. Melada and Yuan Chang, MD, and A. Gregory McClure, MD Arthur E. Pellegrini, MD Arthur S. Levine, MD Patrick S. Moore, MD Donna B. McClure and Kathleen J. Pelusi and Nancy Levine-Arnold, MD Dana L. Morganroth Thomas D. McClure, MD John H. Pelusi Jr., Trustee Lois G. Levy BeeJee Morrison Jennifer G. McComb, MD, and Hairong Peng, MD Michael A. Levy, MD Paul McComb *Donald A. Mosites Shirley Perales Stanley Hurwick Levy, MD John R. McConaghy, MD Steven T. Mosites Anna A. Peris, PharmD, and Barbara Barnes, MD, MS, and Thomas M. Mulroy, Esq. Marshal D. Peris, MD Richard Ley

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 69 DONORS INDIVIDUAL

James P. Covert

n football, offensive linemen are the strength of the offense. created the Pitt School of Medicine’s Vascular Medicine Institute They protect the quarterback and other teammates running (VMI), directed by Mark Gladwin, MD, Distinguished Professor of or catching the ball. Usually the biggest men on the field, Medicine, Jack D. Myers Professor of Internal Medicine, and chair, offensive linemen are known for strength, grit, and heart. Department of Medicine. Mr. Covert calls the partnership a “win.” James P. Covert embodies all of these characteristics. He “We committed the seed dollars, and once Mark got started, Iplayed on the “O line” for three of his four years on the University BOOM, he really took off. He’s a dynamo,” Mr. Covert says. “That of Pittsburgh Panthers football team that went 31–5 in the early passion and energy is what has made VMI so successful.” 1980s. (The quarterback he was protecting then was his Pitt But he also credits another group of contributors that he feels roommate, Dan Marino.) He was a first-round draft pick of the is essential. “People who give us the gift of their blood in order Chicago Bears and a member of the famous 1985 Super Bowl XX for us to treat patients are doing an altruistic act. The dollars we championship team coached by Pitt and National Football League earn that go into the Blood Science Foundation really come from legend Mike Ditka. Mr. Covert’s cocaptain on the Bears’ offense, the community, and I just feel strongly that the money needs to go Walter Payton, called him the “best offensive tackle in the NFL.” back into the community. If we can develop lifesaving therapies for So, what does a professional football player do when he retires people with blood disorders and blood-related diseases through from the game? He continues looking out for others — just in a our research, if we can better the quality of life for people with different way. diseases like sickle cell and hemophilia, then that’s what we need In 2007, after several years in health care sales, marketing, and to do,” says Mr. Covert. acquisition initiatives with different companies, Mr. Covert joined When he was asked to join the Board of Trustees at Pitt in 2014, the Institute for Transfusion Medicine (ITxM) as president and Mr. Covert saw it as another chance to help. chief executive officer.IT xM specializes in transfusion medicine “Pitt has given me so much in my life. I came from a small steel and related services. With its two blood centers, Central Blood mill town near Pittsburgh and grew up and met my wife at Pitt,” he Bank in Pittsburgh and LifeSource in Chicago, it provides nearly says. “As my career since football has gone through changes, Pitt one million units of blood products annually. has prepared me for that. You can’t say that about a lot of places.” One of Mr. Covert’s first goals for ITxM was to create a strategic plan, and a large part of that plan was research. He asked, why not forge a relationship with a biomedical powerhouse right here in Pittsburgh? With Mr. Covert’s guidance, a relationship between ITxM and the University of Pittsburgh was solidified to serve people with and conduct research on blood disorders and blood-related diseases. Using the strength in biomedical research and a joint gift from ITxM’s Blood Science Foundation and ITxM’s subsidiary, the Hemophilia Center of Western Pennsylvania, the partnership

70 *BEFORE AN INDIVIDUAL’S NAME INDICATES THE PERSON IS DECEASED *Dolores Nejak Perri and Alene G. Reynolds Trust Jeannine Scott-Dittoe The Frank E. Rath Spang and John A. Perri, MD James H. Rice Bonnie Seaton Company Charitable Trust Eric A. Peter Jacob R. Richard, MD Joyce A. Seder and Jane Spangler Teresa I. Peters and Jeffery Anthony R. Ricottone, MD Harold B. Seder, MD Kenneth J. Spangler David Peters, Esq. C. Daniel Riggs Jodi Segal, MD, and Aaron Sherber Jeffrey W. Spear, Esq. Suzanne K. Morrissey, MD, and *Paul M. Rike, MD Elizabeth T. Segel and Elaine Specter, Esq., and Daniel P. Petro, MD David P. Segel, MD Howard Alan Specter, Esq. Jennifer G. Gotto, MD, and Andrej A. Petrov, MD Mark Roberts, MD Susan L. Seigel and Valerie J. Stabile Christine and Richard Pfingstler Charles J. Seigel, MD Marc B. Robertshaw Peter A. Statti, MD Terrie and Rodney Piatt Stephen Seiler Roesch Family Charitable Trust Christina M. Steele Cindy J. Piendl Stewart Sell, MD Jane Roesch Charles M. Steiner, Trustee Michael Pignatiello Katherine A. Servich Ann A. Rogers Adam Steinfurth Anne M. Pilewski and Elizabeth A. and James Shaffer Estate of Frances B. Rogers Keith Richard Stephenson, MD Joseph M. Pilewski, MD Patricia A. Shaffer Sandra B. Rogers Kenneth Stepka Debra and James Pingpank Jr., Joan D. Shanahan Rebecca A. and Lawrence D. Stern MD, FACS Stefania Ferrarese Romoff and Jeffrey A. Romoff Thomas Sharratt Maxine B. Stevens, MD Beth H. Piraino, MD, and Barbara S. and Herbert S. Shear Paul M. Piraino Greta Rooney and Susan R. Stewart and Arthur J. Rooney II Gracia V. Sheptak and George L. Stewart II Jodi A. Pitchok Patricia Regan Rooney and Peter E. Sheptak, MD Mary N. Stewart Michael P. Pitterich Ambassador Daniel M. Rooney Stephan R. Sher, DO Marcia M. Stewart and Diane M. and Michael P. Pochron B. Hoagland Rosania, MD Donna M. Sherman *Mervin S. Stewart, MD Terri L. and James C. Polacheck David L. Rosenfeld, MD Gene V. Sherman, MD Lavina J. Stinson and Stephen J. Pollack, MD Alan Nicholas Ross, MD Melissa J. Sherman, MD *Glenn E. Stinson Barbara G. Poolos and Joan and Ronald M. Rothaus Richard A. Shildt, MD Lori Stofman and Guy M. C. James Poolos, MD Stofman, MD, FACS Diane D. Rowe and Ivan A. Shulman, MD David Dixon Porter, MD Kerry B. Stone, MD, and Frank Stone Clifford R. Rowe Jr. Margarita M. Shultz, MD, and Marsha A. Poster, PhD Kimberly E. Rubash and Robert Glenn Shultz, MD H. Donald Stork Palmer F. Posvar and Harry E. Rubash, MD Susan Siems Carol A. Strausbaugh Wesley W. Posvar Jr. Maria E. Rubio *Judy A. Sigal Donna Lou Strawbridge James L. Poth Jr., MD James M. Russavage, DMD, MD Randi B. Sigal and Diane C. Strollo, MD, and Janet M. Potter Jane Curle Rust and James O. Rust Michael B. Sigal, MD Patrick J. Strollo Jr., MD Gabriela Powell Yoel Sadovsky, MD Rhoda F. Sikov Nancy Nan-Szu Sun, MD Charles D. Prestopine Stephen Sakumoto Laura Jean Sill and David C. Sill, MD Elizabeth L. and John P. Surma Monica Protz Karl William Salatka, MD Carl Ian Silverstein Maureen M. Suster, MD Carol S. Provost *Anne Salmon and Rosa L. Pinkus, PhD, and Robert J. Swansiger, MD Donna Puleio, MD *The Honorable J. Quint Salmon Richard L. Simmons, MD Michael Swindell Dale Pysher Marc A. Saltzman, MD Virginia C. Simmons and Christine A. Sypien Joshua Nii Anang Quaye, MD E. Ronald Salvitti, MD Richard P. Simmons, Trustee Cynthia L. Talmadge Robert W. Queale Pablo J. Sanchez, MD Janet Di Pasquale Simon, PhD, and *Julia H. Tamkevicz *J. Matthew Simon, PhD Janet K. Quint Susan C. Santa-Cruz Rita J. Tansky and Karen Rebecca Simon, MD Mindy Goldstein Rabinowitz and Athena Sarris Burton M. Tansky, Trustee Jay Steven Rabinowitz, MD Juliet L. Simonds Candace M. Sarris Victor Tapias Molina, PhD Ronald Rabinowitz, MD Deb and Mark Sindler Belinda Savage-Edwards, MD Judith Tapper and Dr. Margaret V. Ragni Norman A. Sindler Alan J. Tapper, MD Juliette Wait, MD, and Manikantan K. Ramakrishna Michael A. Savin, MD Gurmukh Singh, MD, PhD, MBA Barry S. Tatar, MD John G. Rangos Sr. David and Sara Scaife Bernard F. Slisz D. Lansing Taylor, PhD Barbara Burnham Rankin and Marion Weinman Schafer and Marquis M. Smith Jr. Walter J. Telesz, MD Fred Martin Rankin III Irwin A. Schafer, MD Dr. S. Rush Smith Sandra and Richard Teodori David Rath Michael J. Scheel, MD Walter C. Smith *Esther F. Teplitz, MD Diana Mrvos Rath and Mikell Schenck and Nan Smitherman and Kathleen M. and Louis L. Testoni Frank E. Rath Jr. A. William Schenck III Dr. Thomas C. Smitherman Julie Ann Dobson and Lillian Spang Rath Leslie P. Scheunemann, MD David E. Snyder Chet M. Thaker Shilpa B. Raval, MD Marisa S. Schmitt, MD Rebecca Cost Snyder Harold D. Thomas Jr., MD James I. Raymond, MD Daniel G. Schultz, MD Sally M. and Lee F. Snyder Robert Drexel Thomas, MD Raju C. Reddy, MD Glen E. Schumann Sandy L. Snyder Ann E. Thompson, MD Mary J. Reed, MD Jeffrey J. Schwalm Patricia and William Snyder Mark E. Thompson, MD Lise A. Woodard and Lisa S. Schwartz and Tina Socinski and Mark A. Sara B. Thompson John J. Reilly Jr., MD Andrew B. Schwartz, PhD Socinski, MD Diane S. Thompson, MD, and Scott C. Reinhart, MD Frank Sciurba, MD Lenette M. Solano and Todd Thompson, MD Emelie Renziehausen Trust Allan G. Scott, MD Francis X. Solano Jr., MD Susan M. Dunmire, MD, and Dr. Alan H. Resnick Evelyn Steranka Scott, MD, and Patrick Pangburn and Samuel A. Tisherman, MD Susan Lynn Greenspan, MD, and Craig H. Scott, MD John S. Solters, MD Leigh Tison Charitable Trust Neil M. Resnick, MD Marilyn Scott Geoffrey Tither

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 71 DONORS INDIVIDUAL, CORPORATE AND FOUNDATION

Christine J. Toretti Jerilyn G. Willig Alliance for Cancer Gene Therapy Amyotrophic Lateral Sclerosis Kathy P. Tosh and Amanda Smith Wilson and ALung Technologies Inc. Association Joseph N. Tosh III, Esq. David Oscar Wilson, MD Alzheimer’s Association Andrew Sariochek Memorial Fund Barbara E. Trachtenberg James Arthur Wilson, MD American Academy of Hospice Angler Carpentry LLC Richard T. Trackler, MD John M. Wilson, Esq. and Palliative Medicine Anonymous Donna J. Salsburey, MD, and Jean A. Ryan and Robert L. Wilson American Academy of ARCS Foundation, Pittsburgh Michael A. Tranovich, MD Robert R. Winter Otolaryngology-Head and Chapter Neck Surgery Thomas J. Tredici, MD Timothy F. Witham, MD Arthritis Foundation American Association for The Edith L. Trees Charitable Trust Thomas Witomski, MD Arthurs Malof Group Cancer Research William H. Trippler Charles L. Wood Jr. Arthurs Philanthropic Fund American Association for the Dr. Asher A. Tulsky Asana Medical Inc. Emma Jane Griffith Woolley,MD Study of Liver Diseases Thomas C. Valenza, MD Astellas Pharma US Incorporated William D.G. Wyckoff American Association of Richard J. Van Allan, MD Florence M. Rollwagen and Endocrine Surgeons AstraZeneca Pharmaceuticals LP Victoria M. Woshner and Dr. Lyn J. Yaffe American Association of Athersys Inc. Bennett Van Houten Linda Darby Yankes and Immunologists Autism Science Foundation Phu T. Van Joseph Robert Yankes Jr., MD American Association of AVI Foodsystems Inc. Bethann Vanscoy and Gordon J. Rebecca Yee, MD Plastic Surgeons The Ayco Charitable Foundation Vanscoy, PharmD, MBA, CACP Carl C. Yingling American Board of Orthopaedic B. Braun Medical Inc. James D. VanZandt Surgery Inc. Perry W. Younger, MD Bakery Square Holdings, LP John M. Vautier American Bridge Company Betty Lou Yount Trust Deno F. Barsotti Family Fund Helen G. Vernon and American Cancer Society Princess Anne Williams Yousem, MD, Battelle Col. James Nolan Vernon and Samuel A. Yousem, MD Incorporated Bayer Corporation John Vetere Lin Zhang, MD, and Jian Yu, PhD American College of Laboratory Medicine Foundation Bayer HealthCare The Ethel Vincent Charitable Trust Jian-Min Yuan The Breast Cancer Research Dolores Viverette and American College of Medical Deborah E. and Alfred E. Yudes Jr. Foundation J. Franklin Viverette, MD Toxicology Kimberly S. YunKun Beckwith Family Foundation Justin J. Vujevich, MD American College of Radiology Fr. Kenneth Zaccagnini Bergen County United Way’s William Wagner American College of Rheumatology Linda R. Zajdel Research and Education Charitable Flex Fund David J. Wallace, MD Ornella Zarour and Hassane M. Foundation Bice Cole Law Firm, PL Sara R. Wallenbecker, MD Zarour, MD American College of Surgeons Binational Science Foundation Anne M. Walsh and Kathryn H. Zavadak and American Dermatological Biogen Idec Inc. Christopher J. Walsh, MD Daniel G. Zavadak, MD Association The Birmingham Foundation Deborah A. Walsh William B. Zeiler, MD American Diabetes Association Bison Baseball Inc. Jeffrey W. Wangler C. James Zeszutek American Federation for Blechman Foundation Peter M. Ward, MD Renhong Zhao Aging Research The Raymond and Elizabeth Bloch Anne D. Logan, MD, and Renni Zhao American Foundation for Foundation W. Kenneth Washburn Jr., MD Yutong Zhao Suicide Prevention Blue Marlin Systems Inc. *Barbara R. Watters Margaret R. Zinsky and American Foundation for BNY Mellon Foundation of Lee A. Wawrzynski and Paul J. Zinsky, MD Surgery of the Hand Southwestern Pennsylvania Paul E. Wawrzynski II, MD Suzanne D. Zitelli and American Geriatrics Society Boehringer Ingelheim Dr. Evan L. Waxman Basil John Zitelli, MD Incorporated Pharmaceuticals Inc. Ellen M. Mandel, MD, and David M. Zubrow American Heart Association Inc. The Boeing Company Lawrence W. N. Weber, MD American Lung Association Bohemian Citizens Beneficial Janet F. Wei and American Medical Association Society of Derry Twp. Lawrence M. Wei, MD Foundation Bond, Schoeneck and King, PLLC Jesse A. Weigel, MD American National Skyline Inc. Boston Biomedical Pharma Inc. Karen Werrin and S. Rand ORGANIZATIONS The American Orthopaedic Society Werrin, DDS Boston Scientific Cardiac Rhythm for Sports Medicine Management Patience D. Wessel A. C. Dellovade Inc. American Parkinson Disease Boston Scientific Corporation Kenneth J. Westerheide, MD Association Inc. Abbott Laboratories Bowser Pontiac Inc. Debi Wheeler American Psychiatric Foundation AbbVie Inc. Brain Cancer Awareness 5K, Limited Nancy E. Wheeler American Sleep Medicine ABMRF/The Foundation for Bricklayers and Allied Craftworkers R. James White III, MD, PhD Foundation Alcoholic Research Local 9 Pennsylvania Dr. Marina V. N. Whitman and American Society for Pharmacology Acclarent Inc. Bridges and Company Inc. Dr. Robert F. Whitman and Experimental Therapeutics ACell Inc. BrightFocus Foundation Alan L. Whitney, MD American Society of Cataract and Adlai Stevenson PTA Bristol-Myers Squibb Company Sheila Duignan and Refractive Surgery Foundation AEC Group Inc. Michael I. Wilkins American Society of Hematology Buchanan Ingersoll and Rooney PC Aeras Global TB Vaccine Foundation Charles C. Williams Jr., MD American Society of Nephrology Bumpus Foundation Aesthetic Surgery Education and American Society of Transplantation The Buncher Company Azande W. Williams, Esq., and Research Foundation David C. Williams, MD American Spinal Injury Associates The Jack Buncher Foundation Alcon Laboratories Inc. Jeanne M. Williams and American Textile Company Burns White LLC Alex’s Lemonade Stand Foundation Lawrence E. Williams Amgen The Burroughs Wellcome Fund Richard S. Williams Alital Homes LLC

72 *BEFORE AN INDIVIDUAL’S NAME INDICATES THE PERSON IS DECEASED To that end, the Shears recently made a significant gift and pledged multi-year support to the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter. “There are brilliant, dedicated researchers at UPCI doing trans­ formative, life-saving work,” says Mr. Shear. “This is the type of project the Shear Foundation wants to get behind.” “The Shears are helping us to advance our program in precision medicine, especially in the area of breast and ovarian cancers,” says Nancy Davidson, MD, director of UPCI and UPMC CancerCenter until December 2016. “The funds they’re providing will allow for the sophisticated infrastructure needs such as tissue banking, databases, and analytics needed to support the initiative.” More specifically, the investment will support investigations into the genomics of breast cancer, as well as research projects ranging from work on a specific subtype of breast cancer called lobular cancer to a comprehensive genomic characterization of breast cancer metastases, to understand the molecular pathways that contribute to this advanced and generally lethal stage of the disease. “The work supported by the Shears is focused on translational research — research that extends from the laboratory bench Making Medicine Personal into the communities we serve,” explains Dr. Davidson. “UPMC CancerCenter is optimized for and excels in this type of research.” A FAMILY’S GIFT ADVANCES GENOMICS RESEARCH The work will be led by Adrian V. Lee, PhD, professor of pharma­cology and chemical biology, School of Medicine, and of erb and Barbara Shear created the Shear Family human genetics, Graduate School of Public Health; director of Foundation with their children in August of 2014 Pitt’s Institute for Precision Medicine; and director of the Women’s as a means to fund — and propel — a set of nonprofit Cancer Research Center, a collaboration between UPCI and Magee- organizations and causes whose missions align Womens Research Institute. with their own. They also see their foundation as “The more we heard, the more we wanted to be active and make Han opportunity to teach their grandchildren about the joys and a commitment there,” Mrs. Shear says. “We just think they’re on responsibilities of philanthropy. the cutting edge in a lot of areas.” “We’re still early in the game,” says Mr. Shear, “but we’re While the Shears prefer to maintain a low profile, they agreed making some heartfelt and strategic decisions that we think will to be featured here with a little prodding. have long-term impact. That’s what gets us excited. We want to “If it will help spread the word about this new and exciting help make a measurable difference in areas we really care about.” research in personalized medicine and gene sequencing and if it Mr. Shear is chairman and CEO of the Shear Family Office, inspires other people to contribute in ways that they can,” says which manages the Shear Family Foundation and Shear Family Mrs. Shear, “then it’s the right thing to do.” Investments. Formerly, he was the executive chairman and CEO “The scientific opportunities have never been better, and we of GENCO, where he earned an international reputation for appreciate the Shears’ commitment to support our UPCI investi­ pioneering work in reverse logistics. He grew the family business gators in their quest to develop high-impact ideas that can lead to into the second-largest third-party logistics provider in North advances in our ability to practice molecular cancer medicine,” America, and then sold the company to FedEx in 2014, which says Dr. Davidson. “Their partnership and confidence in our work enabled the Shears to focus on other passions. are extraordinary gifts to our research team and ultimately to The Shear Foundation’s focus areas include medical research, our patients.” hunger insecurity, Jewish causes, and family issues. “We both are interested in and encouraged by the advances we’ve seen in medicine and particularly the progress being made in cancer research,” says Barbara Shear. “We want to help continue this impressive momentum.”

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 73 DONORS CORPORATE AND FOUNDATION

Butler Snow LLP Depomed Inc. Glaucoma Research Foundation The Roy F. Johns, Jr. Family Cadence Pharmaceuticals The Deutsche Bank Americas Glenroy Construction Co. Inc. Foundation The Ann and Frank Cahouet Foundation Robert I. Glimcher Family Johnson and Johnson Foundation Dickie, McCamey and Chilcote PC Foundation Jones Day Canon Business Process Services Inc. J and M DiDonato Family Global Impact Juvenile Diabetes Research Carnegie Mellon University Foundation The Gloria and Thomas R. Kitchen Foundation Caroselli, Beachler, McTiernan, Digestive Care Incorporated Memorial Foundation Karl Storz Endoscopy-America Inc. and Conboy The Donaghue Foundation Goya Foods Great Lakes Kathy Vetere Cancer Research Carroll Burdick and McDonough LLP Doris Duke Charitable Foundation The Grable Foundation Charles E. Kaufman Foundation Celgene Corporation Dow Chemical Company PAC Match Grey Kelly Hotel Inc. Cerner Corporation Drinker Biddle and Reath LLP Gustavus and Louise Pfeiffer Kennametal Foundation CET Training LLC DSF Charitable Foundation Research Foundation Key Environmental Inc. Champs Sports Eagle Pharmaceuticals Inc. H. Mak Inc. Keystone Oaks School District Chapman Properties Easley and Rivers Inc. Hackers for Hope Kimberly-Clark Corporation CHDI Foundation Inc. Eat’n Park Hospitality Group Inc. Haemonetics The Lenore and Howard Klein The Chicago Community Foundation Eisai Inc. Haleski Foundation Foundation Inc. Children’s Brain Tumor Foundation Eli Lilly and Company Hamill Family Charitable Fund Klionsky Foundation Children’s Hospital of Elliott Group Haynsworth Sinkler Boyd, PA KLS – Martin LP Pittsburgh Foundation The Ellison Medical Foundation Health Union LLC Knoechel Heating Co. Chronic Obstructive Pulmonary Emergency Medicine Foundation Healthy Home Construction Laborers District Council of Disease Foundation Inc. Western Pennsylvania Emma Clyde Hodge Memorial Fund Hefren-Tillotson Inc. CJL Engineering Lawrence and Rebecca Stern Endologix Inc. Hemophilia Center of The Cleveland Foundation Western Pennsylvania Family Foundation Inc. Epic Cohen and Grigsby PC Highmark Leath, Bouch and Seekings LLP Ernst and Young LLP Colgate-Palmolive Company Hill Fulwider PC Ledbetter, Cogbill, Arnold and Ethicon Endo-Surgery Harrison LLP Columbus Jewish Foundation Hillman Foundation Evans City Elementary and The Judith A. Lese Breast Cancer The Community Foundation The Audrey Hillman Fisher Middle Schools Foundation Inc. for Greater Atlanta Foundation Eye and Ear Foundation The Leukemia and Lymphoma Society Community Foundation of The Matthew Hillman Fisher Faber Daeufer and Itrato PC Western PA and Eastern OH Foundation Lewis Brisbois Bisgaard and Federated Investors Incorporated Smith LLP Community Human Services Henry L. Hillman Foundation The Fashion Footwear Charitable Life Raft Group Corporation The Hinchman Foundation Foundation of New York Inc. Love Family Foundation Inc. Comptec Inc. Hinkhouse Williams Walsh LLP Fidelity Charitable Gift Fund Lowe Syndrome Association CONSOL Energy Inc. The May Kay Houck Foundation Fight for Sight Lungevity Foundation Consolidated Anti-Aging Foundation Howard Hanna Company The Fine Foundation LXR Travel LLC Constellation HP Inc. Flight Attendant Medical Magee-Womens Research Institute Cook Myosite Howard Hughes Medical Institute Research Institute and Foundation Corcept Therapeutics Huntington National Bank Foot Locker Inc. Malignant Hyperthermia Association Cost Company The Foundation For Jewish Hunton and Williams of the United States Council of Three Rivers American Philanthropies IBEW Local Union No. 5 Manion Gaynor and Manning LLP Indian Center Foundation for Physical Medicine IBM Corporation March of Dimes Foundation Covidien and Rehabilitation IBM Employee Services Center Marstine Family Foundation Cranfill Sumner and Hartzog LLP Michael J. Fox Foundation for IDEO Shirley Hobbs Martin Memorial Fund Crawford Consulting Services Parkinson’s Research Image Associates Inc. Mascaro Construction Company LP Crohn’s and Colitis Foundation Francis Family Foundation Inferno Baseball Inc. of America Mason Contractors Association Franco Associates DBA New Era Park Cubist Pharmaceuticals Matt Mertz Plumbing Inc. Frank Calandra Inc. Integra LifeSciences Incorporated McCarter and English LLP Frank J. and Sylvia T. Pasquerilla International Mental Health Cullen and Dykman LLP McElroy, Deutsch, Mulvaney and Foundation Research Organization CureSearch for Children’s Cancer Carpenter LLP Fujifilm Sonosite Inc. International Society of McGuinn Family Foundation Curves of Mt. Lebanon Furniture City Color Inc. Arthroscopy, Knee Surgery and The McKamish Family CVS Caremark Corporation Wayne Fusaro Pancreatic Cancer Orthopaedic Sports Medicine Cyberonics Research Fund The Institute for Transfusion McKenna Long and Aldridge LLP Cyclic Vomiting Syndrome The Futrell Foundation Medicine McKesson Patient Care Solutions Association Futures Without Violence Janssen Scientific AffairsLLC McKnight Realty Partners LLC Cystic Fibrosis Foundation Gailliot Family Foundation Jefferson Regional Medical Center Meadows Standardbred Foundation Owners Assoc. Cystic Fibrosis Foundation Bill and Melinda Gates Foundation Therapeutics Incorporated Jessica Lin Photography LLC The Medicines Company GENCO The Daisy Foundation Jewish Federation of Medtronic Inc. General Electric Company DeHay and Elliston LLP Greater Pittsburgh MehaffyWeber Genomic Health Incorporated Deloitte Services LP Jewish Healthcare Foundation Melanoma Research Alliance John J. Ghaznavi Foundation Inc. of Pittsburgh Dendreon Mellam Family Foundation Gilead Sciences Incorporated Denise’s People Richard King Mellon Foundation

74 Menasha Corporation Foundation Pennsylvania Breast Cancer Ri.MED Foundation Tailgate for the Cure Inc. Menlo Worldwide Logistics Coalition Ridilla Family Partnership The Nancy Taylor Foundation The Merck Foundation Pennsylvania Lions Hearing Riggs Family Foundation for Chronic Diseases Inc. Research Foundation Miles Against Melanoma 5k PA Rita Allen Foundation Team Danielle Pennsylvania Lions Sight Millennium Pharmaceuticals Roche Organ Transplantation Thompson Hine LLP Conservation and Eye Research Incorporated Research Foundation Thompson Public School Foundation Inc. Milliken and Company Rosebud Mining Company District No. 61 The Pfizer Foundation Inc. Mistick Construction Co. Roswell Park Cancer Institute The Thoracic Surgery Foundation Pfizer Inc. for Research and Education Mizuho America Inc. RSNA Research and Education PGT Trucking Inc. The Tippins Foundation Moody and Associates Inc. Foundation Philip V. and Anna S. Brown RTI International Metals Inc. Torax Medical Inc. Morgan Stanley Smith Barney LLC Foundation Running for Parkinson’s Toyama Prefectural Central Hospital Morton Cure Paralysis Fund The Philadelphia Phillies S. M. Cristall Co. Inc. Triangle Community Foundation Inc. Christopher L. Moseley Foundation Phillips Lytle LLP Salvitti Family Foundation TriState Capital Bank Mosites Construction Company Pinnacle Peak Foods Inc. TriVascular Inc. MQ: Transforming Mental Health DBA Ruth’s Chris Steak House Sarcoma Foundation of America Inc. Truist Musculoskeletal Transplant Pirates Charities Sarris Candies Inc. Tucker Ellis LLP Foundation Pitterich Foundation Savinis, D’Amico and Kane LLC Turftenders Inc. NARSAD Research Institute Inc. Pittsburgh Associates Operating Schenley Park Advisors National Marrow Donor Program Pittsburgh Baseball Club Schiff Hardin LLP UCB Inc. National Multiple Sclerosis Society Pittsburgh Cure Sarcoma Schwab Charitable Fund United Way of Allegheny County National Pancreas Foundation Pittsburgh Emergency Medicine SciQuest Inc. United Way of Butler County National PKU Alliance Foundation SeattleGenetics United Way of Greater Philadelphia and Southern New Jersey National Psoriasis Foundation Inc. The Pittsburgh Foundation Sedgwick LLP United Way of Midland County Navarre Minerals Company Pittsburgh Penguins Foundation Selman Breitman LLP United Way of the Columbia – Navigant Consulting Inc. Pittsburgh Post-Gazette Shadyside Hospital Foundation Willamette Nazareth Family Foundation Pittsburgh Steelers LLC Shirlie and Owen Siegel Foundation United Way of the Greater Triangle The Craig H. Neilsen Foundation PL Restaurant Associates LLC Silhol Builders Supply Co. United Way of Westmoreland County The NephCure Foundation Plastic Surgery Foundation The Juliet Lea Hillman Simonds UPMC Neville Chemical Company Plum Running Mustangs Foundation Alumni Assn. Inc. Urology Care Foundation New Era Park Caps Sisterson and Co. LLP The V Foundation for Cancer New York Yankees PNC Financial Services Group Sleep Research Society Incorporated Research New York Yankees Foundation SmartStyle PNC Wealth Management Vanguard Charitable Nico Corporation Smith and Nephew Inc. POISE Foundation Vasculitis Foundation Smith Moore Leatherwood LLP Normandy Industries Inc. Vautier Communications Inc. The T. Rowe Price Program for The William I. and Patricia S. Norwin Elks Lodge No. 2313 Vujevich Dermatology Associates Charitable Giving Snyder Foundation Novartis Pharmaceuticals PricewaterhouseCoopers LLP W. L. Gore and Associates Inc. Corporation Society for Pediatric Radiology The Procter and Gamble Fund Wabtec Foundation NPS Pharmaceuticals Inc. Society for Vascular Surgery Project Purple Walgreens Specialty Pharmacy Nuance Communications Inc. Solot Family Foundation Pulmonary Fibrosis Foundation Wallace H. Coulter Foundation NWPA APA Poolplayers Solving Kids Cancer The Prader-Willi Syndrome The John D. Walsh Company Inc. Obesity Society Charles F. Spang Foundation Association James F. Walsh Foundation Speed Motor Express of WNY Inc. Olympus Pyrotechnic Management Inc. DBA Speed Global Services We Wish Inc. OMI Refractories LLC DBA Bisco Quagga Accessories LLC Wells Fargo Bank, NA Refractories Spiracur Inc. Questcor Pharmaceuticals Western Pennsylvania School On LLC DBA On Motion Media Splash Water Sports Inc. Incorporated for Blind Children Onyx Pharmaceuticals Inc. St. Clair Hospital Quinn Emanuel Urquhart Westmoreland Country Club Oracle Corporation and Sullivan LLP St. Jude Medical Inc. Whitehall Foundation Incorporated Out of the Woods Foundation Racine, Olson, Nye, Budge The Stanley Medical Research Institute Willcox and Savage PC Ovarian Cancer Research Fund and Bailey William C. Alexander and Company Incorporated Radelet McCarthy Polletta Inc. Stellar Solutions Foundation McGowan Charitable Fund Inc. P. J. Dick Incorporated Architects and Interior Designers Stone Family Foundation Willman and Silvaggio LLP PAA Foundation John G. Rangos Sr. Charitable StoneWood Insurance Company Phillip H. and Betty L. Wimmer Paragon Wholesale Foods Foundation Stork Foundation Family Foundation Paralyzed Veterans of America Reed Smith LLP Stryker Corporation Wings for Life Spinal Cord Research Spinal Cord Research Foundation John Nesbit Rees and Sarah Henne Stryker Endoscopy Foundation Parke Interiors Inc. Rees Charitable Foundation Stryker Neurovascular Samuel and Emma Winters Parkinson’s Disease Foundation Rehabilitation and Neurological Supernus Pharmaceuticals Inc. Services LLC Foundation Joseph A. Patrick Foundation Inc. Surgical Infection Society Renaissance Charitable The Woiner Foundation T. D. Patrinos Painting and Foundation Foundation Inc. World Wide Technology Foundation Contracting Company Susan G. Komen for the Cure RenovaCare Inc. Zubin Custom Homes Inc. Penn Township Police Benevolent Sysco Pittsburgh LLC Zurich American Insurance Association Research to Prevent Blindness Inc. Taiho Pharmaceutical Co., Ltd. Company

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 75 UNIVERSITY OF PITTSBURGH INSTITUTES AND CENTERS UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE SCHOOL OF MEDICINE DEPARTMENTS AGING INSTITUTE DIRECTOR: Charles F. Reynolds III, MD

BRAIN INSTITUTE DIRECTOR: Peter L. Strick, PhD SENIOR VICE CHANCELLOR FOR THE HEALTH DEPARTMENT OF SCIENCES AND JOHN AND GERTRUDE PETERSEN ANESTHESIOLOGY CENTER FOR MILITARY MEDICINE RESEARCH DEAN OF MEDICINE: Arthur S. Levine, MD CHAIR: Howard B. Gutstein, MD DIRECTOR: Rocky S. Tuan, PhD VICE DEAN: Ann E. Thompson, MD, MCCM EXECUTIVE VICE CHAIR: MD MBA CENTER FOR VACCINE RESEARCH Mark E. Hudson, , ASSOCIATE DEANS INTERIM DIRECTOR: Saleem Khan, PhD VICE CHAIRS: Admissions and Financial Aid — Basic Research — Yan Xu, PhD CLINICAL AND TRANSLATIONAL Beth M. Piraino, MD Clinical Operations—Mark E. Hudson, MD, MBA SCIENCE INSTITUTE Continuing Medical Education — DIRECTOR: Steven E. Reis, MD Clinical Research — Jonathan H. Waters, MD Barbara E. Barnes, MD, MS Diversity — William Simmons, MD Faculty Affairs — Dena Hofkosh,MD , MEd DRUG DISCOVERY INSTITUTE Education — David Metro, MD Faculty Development — Ora A. Weisz, PhD DIRECTOR: D. Lansing Taylor, PhD Faculty Development — Rita M. Patel, MD Global Health Education — Pain Medicine — Ajay D. Wasan, MD, MSc Peter J. Veldkamp, MD, MS INSTITUTE FOR CLINICAL RESEARCH EDUCATION EXECUTIVE ADMINISTRATOR: Ed McQuade Graduate Medical Education — Rita M. Patel, MD DIRECTOR: Wishwa N. Kapoor, MD, MPH Graduate Studies — John P. Horn, PhD DEPARTMENT OF Medical Education — John F. Mahoney, MD INSTITUTE FOR PRECISION MEDICINE BIOMEDICAL INFORMATICS Medical Scientist Training Program — DIRECTOR: Adrian Lee, PhD CHAIR: Michael J. Becich, MD, PhD Richard A. Steinman, MD, PhD MAGEE-WOMENS RESEARCH INSTITUTE VICE CHAIR: Gregory F. Cooper, MD, PhD Medical Student Research — DIRECTOR: MD Donald B. DeFranco, PhD; Yoel Sadovsky, ADMINISTRATOR: Rob Cecchetti Gwendolyn A. Sowa, MD, PhD McGOWAN INSTITUTE FOR Physician Scientist Training Program — REGENERATIVE MEDICINE DEPARTMENT OF Richard A. Steinman, MD, PhD CARDIOTHORACIC SURGERY DIRECTOR: William R. Wagner, PhD Postdoctoral Affairs — Darlene F. Zellers, PhD CHAIR: James D. Luketich, MD Student Affairs — Joan Harvey,MD PITTSBURGH INSTITUTE FOR VICE CHAIRS: NEURODEGENERATIVE DISEASES Cardiovascular Services—Victor O. Morell, MD DIRECTOR: J. Timothy Greenamyre, MD, PhD ASSISTANT DEANS Clinical Affairs — Inderpal Sarkaria,MD

Academic Affairs — Saleem Khan,PhD THOMAS E. STARZL Research and Education — Admissions — Kanchan H. Rao, MD TRANSPLANTATION INSTITUTE Jonathan D’Cunha, MD, PhD DIRECTOR: Fadi G. Lakkis, MD Faculty Diversity — Chenits Pettigrew Jr., EdD ADMINISTRATOR: Jean Bunyan

Graduate Medical Education — UNIVERSITY OF PITTSBURGH Frank J. Kroboth, MD CANCER INSTITUTE DEPARTMENT OF CELL BIOLOGY Medical Education — Cynthia Lance-Jones, PhD DIRECTOR: Nancy E. Davidson, MD CHAIR: Alexander D. Sorkin, PhD Medical Education Technology — (Until Dec. 1, 2016) James B. McGee, MD INTERIM DIRECTOR: Edward Chu, MD VICE CHAIR: Simon C. Watkins, PhD Medical Scientist Training Program — ADMINISTRATOR: Sue Conway JoAnne L. Flynn, PhD; Satdarshan (Paul) S. VASCULAR MEDICINE INSTITUTE Monga, MD DIRECTOR: Mark T. Gladwin, MD DEPARTMENT OF Medical Student Research — COMPUTATIONAL AND Judy C. Chang, MD, MPH; Margaret SYSTEMS BIOLOGY Conroy, MD; Brad Dicianno, MD, MS; John R. CHAIR: Ivet Bahar, PhD Fowler Jr., MD; Rebecca P. Hughey, PhD; Cynthia Lance-Jones, PhD VICE CHAIRS: Student Affairs — Chenits Pettigrew Jr.,EdD Faculty Affairs — Panayiotis (Takis) V. Benos,PhD Veterans Affairs — Ali F. Sonel,MD Educational Programs — James R. Faeder, PhD ADMINISTRATOR: Marcia Schwab

76 DEPARTMENT OF DEPARTMENT OF DEPARTMENT OF CRITICAL CARE MEDICINE MEDICINE OBSTETRICS, GYNECOLOGY, AND REPRODUCTIVE SCIENCES CHAIR: Derek C. Angus, MD, MPH CHAIR: Mark T. Gladwin, MD CHAIR: Robert P. Edwards, MD VICE CHAIRS: VICE CHAIRS: VICE CHAIRS: Academic Affairs — Michael R. Pinsky,MD Academic Affairs — Christopher O’Donnell,PhD Clinical Affairs — Isabelle Wilkins,MD Clinical Operations — Arthur J. Boujoukos, MD Clinical Affairs — Michael Donahoe,MD Clinical Operations — Richard Beigi, MD Education — Lori Shutter, MD Clinical Research — Alison Morris, MD, MS Community Practices — Faculty Development — Douglas White, MD Education — Melissa A. McNeil, MD, MPH Edward A. Sandy II, MD, MBA Research — John Kellum, MD Faculty Development — Ora A. Weisz, PhD Education — Gabriella Gosman, MD Resuscitation Research — Patrick Kochanek, MD Quality Improvement and Patient Safety — Faculty Development — Sharon Hillier, PhD INTERIM ADMINISTRATOR: Teri Savolskis Franziska Jovin, MD Gynecological Services — Preclinical Research — Flordeliza S. Harold Wiesenfeld, MD Villanueva, MD DEPARTMENT OF Obstetrical Services — Hyagriv Simhan, MD DERMATOLOGY EXECUTIVE ADMINISTRATOR: Annmarie Lyons Research — Yoel Sadovsky, MD CHAIR: Louis D. Falo Jr., MD, PhD Women’s Health Service Line Specialty ADMINISTRATOR: Jean Bunyan DEPARTMENT OF MICROBIOLOGY AND Services and Referral Physician Relations — MOLECULAR GENETICS John Comerci, MD DEPARTMENT OF CHAIR: Thomas E. Smithgall, PhD ADMINISTRATOR: Jeff Knorr DEVELOPMENTAL BIOLOGY ADMINISTRATOR: Kathleen Rakow CHAIR: Cecilia Lo, PhD DEPARTMENT OF VICE CHAIR: Neil Hukriede, PhD OPHTHALMOLOGY DEPARTMENT OF ADMINISTRATOR: James Kaczynski NEUROBIOLOGY CHAIR: José-Alain Sahel, MD CHAIR: Peter L. Strick, PhD VICE CHAIRS: DEPARTMENT OF VICE CHAIR: Nathan Urban, PhD Business Operations — Alex Anetakis, MD EMERGENCY MEDICINE ADMINISTRATOR: Carolyn Louderback Clinical Operations — Jenny Yu, MD CHAIR: Donald M. Yealy, MD Medical and Resident Education— EXECUTIVE VICE CHAIR: Evan L. Waxman, MD, PhD Clifton W. Callaway, MD, PhD DEPARTMENT OF NEUROLOGICAL SURGERY Ophthalmology Research — Jeffrey Gross,PhD VICE CHAIRS: CHAIR: Robert M. Friedlander, MD, MA Research — Robert L. Hendricks, PhD Clinical Operations — Charissa B. Pacella, MD EXECUTIVE VICE CHAIRS: ADMINISTRATOR: Ed Harrison Graduate Education — Allan B. Wolfson, MD Clinical Operations — David O. Patient Safety and Quality — Okonkwo, MD, PhD DEPARTMENT OF Paul E. Phrampus, MD Surgical Services — Paul Gardner, MD ORTHOPAEDIC SURGERY ADMINISTRATOR: Russell Meyers VICE CHAIR: CHAIR: Freddie H. Fu, MD, DSci (Hon), DPs (Hon) Quality Improvement — Peter C. Gerszten, EXECUTIVE VICE CHAIR: DEPARTMENT OF MD, MPH Orthopaedic Research — Rocky S. Tuan, PhD FAMILY MEDICINE EXECUTIVE ADMINISTRATOR: Patrick Conway VICE CHAIRS: CHAIR: Jeannette E. South-Paul, MD Assistant Residency Program Director — EXECUTIVE VICE CHAIR: James Dewar, MD DEPARTMENT OF MaCalus V. Hogan, MD ADMINISTRATOR: Margaret Ealy NEUROLOGY Clinical Services — William Donaldson III, MD CHAIR: Lawrence R. Wechsler, MD Clinical Outcomes Research — DEPARTMENT OF VICE CHAIRS: James Irrgang, PhD IMMUNOLOGY Academic Affairs — J. Timothy Community Outreach — Mark E. Baratz, MD CHAIR: Mark J. Shlomchik, MD, PhD Greenamyre, MD, PhD Education/Residency Program Director — VICE CHAIR: Dario A.A. Vignali, PhD Clinical Affairs — Maxim Hammer,MD Vincent F. Deeney, MD ADMINISTRATOR: Matthew Barry Research — Steven H. Graham, MD, PhD Pediatric Orthopaedic Surgery — W. Timothy Ward, MD Veterans Affairs — Paula R. Clemens,MD Quality Management — Adolph Yates, MD ADMINISTRATOR: Patrick Conway ADMINISTRATOR: Andrea Badway

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 77 DEPARTMENT OF DEPARTMENT OF DEPARTMENT OF OTOLARYNGOLOGY PHYSICAL MEDICINE AND SURGERY REHABILITATION CHAIR: Jonas T. Johnson, MD CHAIR: Timothy R. Billiar, MD CHAIR: Gwendolyn A. Sowa, MD, PhD VICE CHAIRS: VICE CHAIRS: VICE CHAIRS: Clinical Operations — Robert L. Ferris, MD, PhD Clinical Services — Andrew B. Peitzman, MD Faculty Academic Development — Education — David Eibling, MD Education — Kenneth Lee, MD Amy K. Wagner, MD Quality and Patient Safety — Carl H. Oncology Services — David Bartlett, MD Medical Education — Wendy Helkowski, MD Snyderman, MD, MBA Quality — Kevin Garrett, MD Pediatric Rehabilitation — Amy Houtrow, MD, MPH EXECUTIVE ADMINISTRATOR: Ed Harrison Research — Allan Tsung, MD, and Research — Michael L. Boninger, MD Michael Lotze, MD Strategic Planning and Development — DEPARTMENT OF Transplantation Surgery — Abhinav Humar, MD PATHOLOGY Michael Munin, MD ADMINISTRATOR: Ed McQuade CHAIR: George K. Michalopoulos, MD, PhD ADMINISTRATOR: Monica Tietsworth EXECUTIVE VICE CHAIR: DEPARTMENT OF Anatomic Pathology — Samuel A. Yousem, MD DEPARTMENT OF UROLOGY PLASTIC SURGERY VICE CHAIRS: CHAIR: Joel B. Nelson, MD CHAIR: J. Peter Rubin, MD Enterprise Development — Rajiv Dhir, MBBS, MBA EXECUTIVE VICE CHAIR: Michael C. Ost, MD VICE CHAIR: Joseph E. Losee, MD Faculty Mentorship — Charleen Chu, MD, PhD VICE CHAIRS: ADMINISTRATOR: Jean Bunyan Experimental Pathology — Clinical Operations — Ronald M. Benoit, MD Satdarshan (Paul) S. Monga, MD Quality Improvement and Patient Safety — DEPARTMENT OF Laboratory Medicine — Alan Wells, MD, DMSc Timothy D. Averch, MD PSYCHIATRY Molecular Genomic Pathology — ADMINISTRATOR: Margaret Ealy CHAIR: David A. Lewis, MD Yuri Nikiforov, MD, PhD VICE CHAIR: Clinical Affairs — ADMINISTRATOR: Brian Rudolph Kenneth C. Nash, MD, MMM ADMINISTRATOR: Lori Zippay DEPARTMENT OF PEDIATRICS DEPARTMENT OF CHAIR: Terence Dermody, MD RADIATION ONCOLOGY VICE CHAIRS: CHAIR: Joel S. Greenberger, MD Clinical Affairs — A. Kim Ritchey,MD VICE CHAIR: Clinical Research — Alejandro Hoberman, MD Clinical Affairs — Dwight E. Heron,MD , MBA Translational Research — Jay J. Kolls, MD ADMINISTRATOR: Stephanie Dutton VICE PRESIDENT AND CHIEF FINANCIAL OFFICER, CHILDREN’S HOSPITAL OF PITTSBURGH OF UPMC: Nicholas Barcellona DEPARTMENT OF RADIOLOGY CHAIR: Jules Sumkin, DO DEPARTMENT OF PHARMACOLOGY AND VICE CHAIRS: CHEMICAL BIOLOGY Clinical and Academic Affairs — CHAIR: Bruce A. Freeman, PhD Mitchell Tublin, MD VICE CHAIRS: Quality Assurance and Strategic Development — Margarita Zuley, MD Academics — Michael Palladino, PhD VICE PRESIDENT OF UPMC IMAGING SERVICES: Medical Education — Donald B. DeFranco, PhD Laura Gailey Moul Graduate Education — Patrick Pagano, PhD Precision and Translational Pharmacology — DEPARTMENT OF Steffi Oesterreich,PhD STRUCTURAL BIOLOGY Research — Edwin Levitan, PhD CHAIR: Angela Gronenborn, PhD ADMINISTRATOR: James Kaczynski EXECUTIVE ADMINISTRATOR: Dean Duncan

78 BOARD OF VISITORS (AS OF SEPTEMBER 30, 2016)

Robert J. Alpern, MD Dean and Ensign Professor of Medicine, Yale School of Medicine

G. Nicholas Beckwith III Chairman and Chief Executive Officer, Arch Street Management LLC; Chairperson, Board of Directors, UPMC

Edward J. Benz Jr., MD President and Chief Executive Officer Emeritus, Dana-Farber Cancer Institute

Emery Neal Brown, MD, PhD Edward Hood Taplin Professor of Medical Engineering and Professor of Computational Neuroscience, Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology

Catherine D. DeAngelis, MD, MPH University Distinguished Service Professor Emerita and Professor of Pediatrics Emerita, Johns Hopkins University School of Medicine

Julie A. Freischlag, MD Vice Chancellor for Human Health Sciences and Dean, School of Medicine, University of California, Davis

Samuel Hawgood, MBBS Chancellor and Arthur and Toni Rembe Rock Distinguished Professor, University of California, San Francisco

J. Larry Jameson, MD, PhD Executive Vice President, University of Pennsylvania for the Health System, and Dean, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania

Vivian S. Lee, MD, PhD, MBA Senior Vice President for Health Sciences, University of Utah; Dean, University of Utah School of Medicine; CEO, University of Utah Health Care

William K. Lieberman President, W. K. Lieberman Company LLC

Paul G. Ramsey, MD CEO, UW Medicine; Executive Vice President for Medical Affairs and Dean, School of Medicine, University of Washington

Arthur H. Rubenstein, MBBCh Professor of Medicine, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania

Jack D. Smith, MD Director of Orthopedics, Excela Health; Chair, Excela Health Orthopedic Surgery

Allen M. Spiegel, MD Marilyn and Stanley M. Katz Dean, Albert Einstein College of Medicine; Executive Vice President and Chief Academic Officer, Montefiore Medicine

Steven A. Wartman, MD, PhD President and Chief Executive Officer, Association of Academic Health Centers

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE 79 CREDITS PHOTOGRAPHERS AND ILLUSTRATORS Paul Brittenham, page 40 Adam Cruft, page 17 This report was produced by the Office of Academic Affairs, Health Sciences. Joshua Franzos, pages 2, 7, 9, 10, 25 Margaret C. McDonald, PhD, MFA Alessandro Gottardo, pages 18, 32, 56 Associate Vice Chancellor for Academic Affairs David Kelly, page 62 Lisa K. Barsom, PhD Cami Mesa, page 20 Assistant Vice Chancellor for Academic Affairs Mike Nudelman, page 8 Lisa Lorence Director of Academic Programs Annie O’Neill, pages 21, 26–29, 70 Chuck Staresinic University of Pittsburgh Center for Director of Communications Teaching and Learning, pages 14–15, 31 UPMC Creative Services, page 73

STAFF Michele Baum OTHER IMAGES Brandon Copp-Millward COURTESY OF: Keith Gillogly Pages 4–5: Payette Megan Hall, MPPM Page 6: Inserm/Patrick Delapierre Maureen Passmore, MA, MFA Teekie Smith, MSW Page 9: Science family of journals Cathy Steinitz Page 11: Tsinghua University William Tanner Pages 12–13: Official White House photo Special production assistance provided by Lawrence Jackson by Sandra Honick, Barbara Good, and Page 30: Sangki Oak Linda Riner, Office of Faculty Affairs, Page 34: NASA (background), Rocky Tuan School of Medicine, University of Pittsburgh; (top), Ri.MED Foundation (bottom) Beth Ann Conway, Medical and Health Sciences Foundation, University of Page 43: Peter Strick Pittsburgh and UPMC; and Gayle L. Tissue Page 44: Kara Bernstein Kaloyeropoulou, UPMC CancerCenter/ University of Pittsburgh Cancer Institute. Page 47: Carolyn Coyne Page 48: Mark Shlomchik University of Pittsburgh Page 52: Roberto Di Maio School of Medicine 401 Scaife Hall Page 53: Brian Davis 3550 Terrace Street Page 55: Guillermo Calero Pittsburgh, PA 15261 Pages 58–59: © 2016 Pittsburgh Post-Gazette, 412-648-8975 all rights reserved, reprinted with permission www.medschool.pitt.edu Page 60: Tribune-Review The University of Pittsburgh is an affirmative Page 64: UPMC Center for Health Security action, equal opportunity institution. Page 67: Health Sciences Library System

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On the cover: Adaptation in nature, as demonstrated by four birds from the genus Geospiza, which is endemic to the Galapagos Islands and was famously depicted in The Zoology of the Voyage of the H.M.S. Beagle, by Charles Darwin and John Gould

UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE medschool.pitt.edu