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