Stand Up to Cancer” Team Will Pit Immune System Against Pancreatic Cancer 

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A new three-year, $8.1 million grant from the Stand Up to Cancer (SU2C)-Lustgarten Foundation will support an inno­vative project led by Jeffrey Drebin, M.D., the John Rhea Bar­ton Professor and chair of the Department of Surgery. The project will investigate the use of powerful, new drug combinations to help jumpstart the immune sys­tem to better fight pancreatic cancer. 

This is the fourth round of SU2C pancreatic cancer funding awarded to multi-in­stitutional teams with Penn Medicine at the helm, bring­ing the total amount to nearly $40 million since 2009. The new “Dream Team” effort involves researchers from Mount Sinai, the Fred Hutchinson Cancer Research Center, Harvard Medical School, and Memorial Sloan Kettering.

The new “Dream Team” will attempt to exploit the ability of vitamin D to infiltrate T cells into treated tumors by adding another player to the offensive line: checkpoint inhibitors. The newer immunotherapy drug, called nivolumab, has been shown to activate T cells that successfully attack cancers, in­cluding melanoma and lung cancer.

“This project represents a novel team science approach to stimulating T cell immunity in pancreatic cancer patients,” Drebin said. “It will involve scientific principals from across the disciplines: clinical oncologists, basic and translational re­searchers, computational biologists and theoretical scientists. It’s this type of approach that will help us uncover more about the intricate relationship between the pancreatic tumors and the microenvironment and the immune system. We’ve made great progress in this area in a relatively short time span, but there are still many unknowns, and potentially untapped re­sources, like immunotherapies, for us to explore.”

Penn Alzheimer’s Disease Center to Receive $8.8 Million in NIH Funding

The University of Pennsylvania’s Alzheimer’s Disease Core Center (ADCC) has been awarded an estimated $8.8 million over five years from the National Institute on Aging to con­tinue its mission of investigating mechanisms, diagnostics, treatments and strategies for Alzheimer’s Disease (AD) and related dementias.

Discoveries from Penn’s center have advanced understand­ing of the development and progression of AD and related neurodegenerative dementias over the past 25 years, leading to national and international recognition of its research ac­complishments.

“This funding will allow us to build on these successes,” said John Q. Trojanowski, M.D., Ph.D., G.M.E. ’80, the William Maul Measey-Truman G. Schnabel Jr., M.D., Professor of Geriatric Medicine and Gerontology. He is also a professor of pathology and laboratory medicine and founding director of the Penn ADCC.  

Penn Medicine Researchers to Co-lead $23 Million HIV Cure Grant

HIV researchers at the Perelman School of Medicine and the Wistar Institute will co-lead a five-year, $23 million grant from the National Institutes of Health. It is part of the second iteration of the Martin Delaney Collaboratory: Towards an HIV-1 Cure program, which aims to advance basic medical science toward a cure for the disease.

James L. Riley, Ph.D., a research associate professor of microbiology, and Luis J. Montaner, D.V.M., D.Phil., director of the HIV-1 Immunopathogenesis Laboratory at the Wistar Institute Vaccine Center, will serve as co-principal investigators for the “BEAT-HIV: Delaney Collaboratory to Cure HIV-1 Infection by Combination Immunotherapy” consortium, which includes 30 top HIV researchers from institu­tions across the nation, half of whom hail from Penn. The scientific team will work with government, non-profit, and industry partners to test combinations of several novel immunotherapies and gene therapies under new preclinical research and clinical trials.  Other institutions include Philadelphia FIGHT, Rockefeller Univer­sity, VA San Diego Healthcare System, Johns Hopkins University, the University of Nebraska-Lincoln, and the University of Utah.

Other Penn researchers include Faten Aberra, Katharine Bar, Michael Betts, Frederic Bushman, Susan Ellenberg, Ian Frank, Beatrice Hahn, George Shaw, Julie Jadlowsky, Carl June, David Metzger, Pamela Shaw, Pablo Tebas, and E. John Wherry.  

Penn Medicine Hospitals Shine

Penn Medicine hospitals have once again been ranked among the top 10 hospitals in the nation and #1 in Pennsylva­nia by U.S. News & World Report. Together, the combined en­terprise of the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center is ranked as the 9th best hospital in the United States for the magazine’s 2016-2017 annual survey. Once again, the hospitals are also ranked #1 in the Phila­delphia metro area.

Penn Medicine is among only 20 institutions – and the only one in the Philadelphia region – to be named to the publication’s 2016-2017 Honor Roll. The hospitals are also recognized for excellence in 11 specialties, including Cancer; Cardiology and Heart Sur­gery; Diabetes and Endocrinology; Ear, Nose & Throat; Gastro­enterology & GI Surgery; Geriatrics; Nephrology; Neurology and Neurosurgery; Orthopedics; Pulmonology; and Urology.

Three other Penn Medicine hospitals also netted honors. Pennsylvania Hospital is ranked #4 in Philadelphia and #7 in the state and is nationally ranked in Orthopedics. Chester County Hospital is ranked #6 in the Philadelphia region and 12th in the state. Lancaster General Health is ranked 5th in the state and nationally ranked in Gastroenterology & GI Surgery and Pulmonology.

Penn Software Helps to Identify Course of Cancer Metastasis

Individual cells within a tumor are not all the same. This may sound like a modern medical truism, but it wasn’t very long ago that oncologists assumed that taking a single biopsy from a patient’s tumor would be an accurate reflection of the physiological and genetic makeup of the entire mass. Re­searchers have come to realize that cancer is a disease driven by the same “survival of the fitter” forces that, according to Darwin, drove the evolution of life on Earth. In the case of tu­mors, however, individual cells are constantly evolving as a tu­mor’s stage advances. Mobile cancer cells causing metastasis are a deadly outcome of this process.

Tumors also differ among patients with the same type of cancer, so how is a physician able to prescribe a tailored regi­men for the patient? To start to address this conundrum, an interdisciplinary team from the Perelman School of Medicine and the Wharton School developed Canopy, an approach to infer the evolutionary track of tumor cells by surveying two types of mutations – somatic copy number alterations and single-nucleotide alterations – derived from multiple samples taken from a single patient. The researchers demonstrated the approach on samples from leukemia and ovarian cancer, along with samples from a human breast cancer cell line.

The team – Yuchao Jiang, a doctoral student in the Genomics and Computational Biology program; Yu Qiu, Ph.D., a post­doctoral researcher in the lab of coauthor Andy J. Minn, M.D., Ph.D., an assistant professor of radiation oncology; and Nancy R. Zhang, Ph.D., an associate professor of statistics in the Wharton School – published its findings online in the early edition of the Proceedings of the National Academy of Sciences.

“The makeup of a tumor for a given patient is often a mix­ture of multiple distinct cell populations that differ in genetic makeup, gene expression, and physiology,” Jiang said. “This heterogeneity contributes to failures of targeted therapies and to drug resistance based on old thinking that tumors are ho­mogenous masses.” 

They Said It

Fatigue comes in different flavors. “There’s physical fatigue, but also emotional fatigue and psychological fatigue,” said Anne R. Cappola, M.D. ’94, Sc.M., a professor in the Division of Endocrinology, Diabetes, and Metabolism. As she told Prevention, “People underestimate the effects of psychological stress on energy levels, but in retrospect, after that stress is gone, they realize that was making them so tired.”

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“Everyone recognizes the problems that per­vade end-of-life care and, because of that broad recognition, everyone is interested in a solu­tion,” Scott D. Halpern, M.D. ’03, Ph.D. ’02, an associate professor of medicine, epidemiol­ogy, and medical ethics and health policy, told The Philadelphia Inquirer. A critical care physi­cian, he also directs the FIELDS program, Fos­tering Improvement in End-of-life Decision Sci­ence. According to Halpern, the problem is that many people have jumped in with well-in­tended, intuitively appealing programs that may not work. Those could crowd out opportunities for more effective approaches. Among the pop­ular programs that Halpern criticizes are Five Wishes, Respecting Choices, and the Conversa­tion Project. “None of these things are backed by much evidence,” he said. Halpern is most critical of POLST (Physician Orders for Life-Sus­taining Treatment) programs, arguing that they are inflexible while illness is unpredictable.

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A family’s rapport with the nursing staff can improve the care a patient receives, but some­times families can go too far in challenging medical expertise. “When families get stressed, they sometimes go outside their role,” Karen M. Anderson, R.N., M.S.N., told The Wall Street Journal. “They want to determine care or start trying to dictate things.” For example, ac­cording to Anderson, a clinical nurse specialist in patient- and family-centered care at HUP, family members may ask a nurse to increase a patient’s pain medication above the prescribed dose. “You have to trust the doctor had reasons, or the nurse knows when to increase the dose.”

Honors & Awards

Ronald M. Fairman, M.D., G.M.E. ’84, the Clyde F. Bark­er-William Maul Measey Professor of Surgery and chief of vascular surgery and endovascular therapy, was elected a member of the American Philosophical Society. The Philadel­phia society promotes useful knowledge in the sciences and humanities and has played a role in American cultural and in­tellectual life for more than 250 years. Fairman, a professor of surgery in radiology at HUP, also serves as vice chairman for clinical affairs for the Department of Surgery. He has played a central role in shaping a new field of medicine, endovascular therapy, which helps patients afflicted with blood vessel disor­ders, such as aneurysms and arterial blockages. He is presi­dent of the Society for Vascular Surgery.

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Harold I. Feldman, M.D., M.S.C.E. ’91, the George S. Pepper Professor of Public Health and Preventive Medi­cine, became president of the American College of Epi­demiology in September. The College is the profes­sional organization of the nation’s epidemiologists – health professionals who ex­amine patterns of diseases such as cancer, obesity, food poi­soning, and influenza, and their causes, which range from lifestyle choices, to environmental exposures, to genetic fac­tors.  The chair of the Department of Biostatistics and Epide­miology and director of the Center for Clinical Epidemiology and Biostatistics, Feldman will also become editor in chief of the American Journal of Kidney Diseases, the official journal of the National Kidney Foundation.

Garret A. FitzGerald, M.D., chair of the Department of Systems Pharmacology and Translational Therapeutics and di­rector of the Institute for Translational Medicine and Thera­peutics, was elected to the Royal Irish Academy. It is considered the highest aca­demic honor in Ireland. Fitz­Gerald was recognized for his lifetime contributions to the study of cardiovascular health. He was instrumental in the discoveries relating to the use of low-dose aspirin in preventing cardiac disease. His team was the first to pre­dict and then mechanistically explain the cardiovascular haz­ard from NSAIDs, and his laboratory was also the first to dis­cover a molecular clock in the cardiovascular system.

More recently, FitzGerald also received a 2016 Presidential Distinguished Service Award for the Irish Abroad. He is the first recipient in the new category of Science, Technology, and Innovation. In addition to acknowledging FitzGerald’s research, the Service Award noted his work in promoting scientific endeavor in Ireland, including establishing the Center for Cardiovascular Science at University College, Dublin, and serving as founding advisor of Science Founda­tion Ireland.  

Farzana Rashid Hossain, M.D., an assistant professor of clinical medicine and a gastroenterologist, was appointed by Mayor Jim Kenney to the Philadelphia Commission for Women. The commission’s goal is to build vital relationships and help create equitable op­portunities for women at all levels of the Philadelphia workforce. Rashid Hossain said, “I hope to empower girls to follow their scientific passions and take an execu­tive pathway from the lab to the boardroom and look for­ward to working with my new colleagues to demon­strate that capable women are essential in strategizing and executing long-lasting govern­ment policy matters that will enable equal rights for women.” Her honors include the Health Care Heroes Award from Penn Medicine, and she serves on the board of the Self-Freedom Foundation, which funds projects in the areas of education, critical health care, and special situations that directly benefit underprivileged women and children in developing countries.

Martin G. St. John Sutton, M.B., B.S., a John W. Bryfogle Emeritus Professor of Cardiovascular Medicine, has received the 2016 Lifetime Achievement Award from the American Society of Echocardiography for his pioneering contributions to structural and functional ventricular remodeling and repair. “Martin’s work codified the tools we now commonly use to quantify changes in size, shape, and function of the heart un­der many conditions, which has become the foundation for all subsequent studies of ventricular remodeling,” said Victor A. Ferrari, M.D. ’86, a Penn professor of cardiovascular medicine. “His studies of reverse – or beneficial – remodeling using Cardiac Resynchronization Therapy were groundbreaking and led the field in a completely new direction.” 

St. John Sutton directed Penn’s Cardiovascular Imaging Division from 1993 to 2014 and the Center for Quantitative Echocardiography for 20 years. Over the course of his career, he was  also co-author of more than 320 peer-reviewed publications in heart failure, congenital heart disease, and echocardiography.

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Raymond R. Townsend, M.D., a professor of medicine and director of the Hypertension Program, was named the 2016 Physician of the Year by the American Heart Association (AHA). The award is presented to one person each year with direct pa­tient care responsibilities who has demonstrated an exemplary commitment to furthering the association’s mission to build healthier lives, free of cardio­vascular diseases and stroke. 

“Having spent the majority of my career dedicated to hypertension, both in re­search and clinical practice, I have been actively involved in the AHA as their mission goes hand in hand with my career goals,” Townsend said. He received his first award from the association in 1984, which was also his first-ever academic grant. Later, he became an AHA fellow, and he has been a reviewer and contributor for Hypertension, the associa­tion’s journal, for more than 20 years.

Douglas C. Wallace, PhD., a professor of pathology and lab­oratory medicine at Penn and director of the Center for Mito­chondrial and Epigenomic Medicine at Children’s Hospital, was inducted into the Italian Academy of Sciences. Members have included such luminaries as the Italian scientists Volta, Golgi, and Avogadro and non-Italians Pasteur, Frank­lin, and Einstein. Wallace was recognized for his scientific contributions as the founder of the field of mitochondrial medicine. During the 1970s, he defined the genetics of the DNA located in the mito­chondria, the “power plants” of the cell, including demonstrating that human mitochondrial DNA is exclusively maternally inherited. The mitochondrial DNA codes for the wiring diagram of the power plants. Wal­lace has proposed and synthesized evidence for a hypothesis that mitochondria are not just a useful tool to trace the history of evolution but may have played a critical role in shaping how predecessors of modern humans adapted to their environments. 

E. John Wherry, Ph.D., a professor of microbiology, direc­tor of the Institute for Immunology, and co-director of the Parker Institute for Cancer Immunotherapy at Penn, received the 2016 Frederick W. Alt Award for New Discoveries in Im­munology from the Cancer Research Institute (CRI). The award honors an outstanding former CRI-Irvington postdoc­toral fellow. Wherry was a CRI-Irvington postdoctoral fellow from 2000 to 2003 at Emory University.

Wherry’s discoveries include insights into how changes in gene expression affect T cell exhaustion. Normally, during a short-term infection, such as the flu, immune cells handily eliminate the offending pathogen. But in long-term chronic infections such as hepatitis C, HIV, and malaria – and also in cancer – T cells and the opposing pathogen or malignancy engage in a continuous struggle, and over time the T cells be­come “exhausted,” giving cancer or the pathogen the edge.

Appointments

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Ramon Diaz-Arrastia, M.D., Ph.D., has been named the ninth Presidential Professor at the University of Pennsylvania. A world-leading expert in traumatic brain injury, Diaz-Arras­tia is the Presidential Professor of Neurology in the Perelman School of Medicine. “At the uncharted frontier of brain sci­ence and traumatic injury, few investigators have expanded our knowledge quite like Dr. Ramon Diaz-Arrastia,” said Penn president Amy Gutmann. “Ramon is a pioneering force in ex­ploring the intricacies of neural damage and repair, and as Presidential Professor he will further strengthen Penn’s vital neurological research and exceptional clinical care.” 

Diaz-Arrastia joins Penn from the Uniformed Services University of the Health Sciences in Bethesda, Md., where he also served as director of clinical research at the Cen­ter for Neuroscience and Regenerative Medicine, a partner­ship between the USUHS and the National Institutes of Health. His path-breaking research focuses on understand­ing the molecular, cellular, and tissue level mechanisms of secondary neuronal injury and neuroregeneration, espe­cially through biomarker development. His most recent work explores using MRI, functional MRI, and PET scan­ning to characterize the multiple complex mechanisms in­volved in traumatic injury to the brain, as well as combining imaging, genomic, and tissue biomarkers to better predict patient outcomes after traumatic brain injuries and to de­velop novel therapies.

Diaz-Arrastia earned his M.D. degree in 1988 and his doctor­ate in biochemistry in 1986 from Baylor College of Medicine.

Regina Cunningham, Ph.D., R.N., was named senior vice president and chief nursing executive for the University of Pennsylvania Health System. She continues in her current role as the Hospital of the University of Pennsylvania’s chief nurs­ing executive.

“Regina’s expanded portfolio reflects the broad impact and crucial importance of nursing as Penn Medicine continues to expand and innovate across the continuum of care,” said Ralph W. Muller, CEO of UPHS. “During her tenure thus far at Penn Medicine, Regina has forged strong partnerships to deepen nursing’s role across the health system.”

In her new role, Cunning­ham provides leadership to nursing colleagues from each entity throughout UPHS. Her close collaboration with Patrick J. Brennan, M.D., chief medical officer and se­nior vice president, to ad­vance interprofessional col­laborations across the system will continue, and she will partner with Antonia Villarruel, Ph.D., R.N., dean of Penn’s School of Nursing, to advance scholarly platforms for nursing across Penn Medicine.

Cunningham is currently principal investigator of an NIH-funded multi-site study aimed at developing knowledge and skills to support implementation of clinical trials. She was inducted into the American Academy of Nursing in 2014.

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Maria A. Oquendo, M.D., an internationally renowned ex­pert in mood disorders, has been appointed the new chair of the Department of Psychiatry. Oquendo, who will begin her new role at Penn Medicine on January 1, 2017, is currently a faculty member at Columbia University, where she is vice chair for education and director of residency training at the New York State Psychiatric Insti­tute. She is also the current president of the American Psychiatric Association.

Oquendo is an interna­tional leader in the treatment and neurobiology of mood disorders, with a special fo­cus on suicide, as well as global mental health. As an investigator, Oquendo has been continuously funded by the National Institute of Mental Health since 1999 and has more than 300 peer-reviewed publications. In addition, she is president of the International Academy for Suicide Research. 

Oquendo received her M.D. degree from the College of Physicians and Surgeons at Columbia University in 1984. 

She completed her residency in psychiatry at the Payne Whitney Psychiatric Clinic at the New York Hospital-Cornell Medical Center.

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