From left: Pablo Tebas, Carl June, and Bruce Levine.
Researchers from the Perelman School and and the Penn Center for AIDS Research (CFAR) have been awarded $7.5 million over five years by the National Institutes of Health to initiate a multi- project HIV study. Its goal: to investigate a new gene therapy approach to render immune cells of HIV-positive patients resistant to the virus.
The project includes principal investigator James L. Riley, Ph.D., associate professor of microbiology; Pablo Tebas, M.D., director of the AIDS Clinical Trials Unit at Penn’s CFAR; James A. Hoxie, M.D. ’76, professor of medicine and director of CFAR; E. John Wherry, Ph.D., professor of microbiology and director of the Institute for Immunology; Frederick D. Bushman, Ph.D., professor of microbiology; and, from Sangamo Biosciences, Inc., Michael C. Holmes, Ph.D., vice president for research.
The Penn-led team, in collaboration with Sangamo, will investigate the ability of a synthetic molecule consisting of a viral entry inhibitor called C34 fused to CXCR4, an HIV co-receptor used by the virus to enter and infect T cells. Building upon the success of past studies such as the one recognized by the Clinical Research Forum, the new Penn project – in both preclinical and clinical studies – aims to safely build an army of modified T cells in HIV-infected patients that are resistant to HIV. They will use a lentiviral technology to express the C34-CXCR4 molecule. This approach, researchers believe, will make more CD4 T cells resistant to the virus and thus may re-invigorate the immune response to control HIV-1 replication in the absence of antiretroviral drug therapy (ADT).
The grant is funded under NIH’s U19 Research Program, which funds collaborative projects involving multiple institutions, including an industry collaborator.
Gene Therapy Efforts Honored
In April, researchers from the Perelman School and CFAR were named among the 2015 recipients of the prestigious Clinical Research Achievement Award. They were honored for their personalized gene therapy work in HIV. The team included Carl H. June, M.D., the Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine; Bruce L. Levine, Ph.D., the Barbara and Edward Netter Professor in Cancer Gene Therapy in the Department of Pathology and Laboratory Medicine and the director of the Clinical Cell and Vaccine Production Facility; and Pablo Tebas, M.D., of CFAR.
At its annual awards ceremony, the Clinical Research Forum recognized the 10 most outstanding research papers written by teams from across the nation. The winning papers were chosen based on their degree of innovation from a pool of more than 50 nominations from 30 research and academic health centers nationwide. The Forum and its supporters believe these papers represent the best work in the field and will lead to advancements in medicine that will change lives and patient outcomes worldwide.
The Penn team’s work, published in the New England Journal of Medicine in March 2014, was the first successful clinical test of any gene-editing approach in humans. In the phase I study, they engineered the immune cells of 12 HIV-positive patients to resist the HIV infection, by mimicking a naturally occurring mutation that occurs in a very small number of people and renders their cells resistant to HIV infection. The researchers used a zinc finger nuclease technology to induce the genetic CCR5 mutation in patients’ T cells to lock out HIV. The modified T cells persisted in all patients, they found, and reduced viral loads in some who were taken off treatment entirely.
– Steve Graff
UPHS Welcomes Lancaster General
The University of Pennsylvania Health System has reached a final agreement for Lancaster General Health (LG Health) to join UPHS. A three-hospital health system located in South Central Pennsylvania, LG Health has been recognized regionally and nationally for its patient-centered services, clinical excellence, patient safety. It has also been designated a Magnet hospital for nursing excellence three times. As Ralph Muller, CEO of Penn’s Health System, put it, “Increasingly, medicine is a team sport,” adding that “we share a passion for excellence, aimed at improving health and providing more value at less cost.” Joining two of the state’s top health systems will build on the strengths of each, allowing them to provide better health-care services to more people. In addition, Penn is exploring opportunities to increase the number of medical students and residents who spend time at Lancaster General Hospital. The detailed agreement is subject to various state and federal reviews before moving ahead.
New to the Academy
Two researchers from the Perelman School of Medicine have been elected to the American Academy of Arts and Sciences, one of the nation’s most prestigious honorary societies and a leading center for independent policy research.
The new honorees, who join 23 other Penn Medicine experts previously elected, are Jean Bennett, M.D., Ph.D., the F. M. Kirby Professor of Molecular Ophthalmology, and Paul A. Offit, M.D., the Maurice R. Hilleman Professor of Vaccinology and Professor of Pediatrics at the Perelman School as well as Professor in the Division of Infectious Diseases at The Children’s Hospital of Philadelphia.
Bennett studies the molecular genetics of inherited retinal degenerations, seeking to develop rational approaches to treat these diseases. Her laboratory reported the first gene therapy success in slowing the disease process in an animal model of inherited retinal degeneration. Her team’s successful preclinical studies on an inherited blinding disease, Leber congenital amaurosis, led to human clinical trials for this disease that have been successful in improving sight. An elected member of the Institute of Medicine of the National Academy of Sciences, she has received the William Osler Award for Patient Oriented Research from the Perelman School.
Offit is co-inventor of a rotavirus vaccine that has been credited with saving hundreds of lives every day. He has been a member of the Advisory Committee on Immunization Practices of the Centers for Disease Control and directs CHOP’s Vaccine Education Center. He is the author of several books in the popular press, including one disputing the claim that vaccines are associated with autism. An elected member of the Institute of Medicine, Offit also received the Lindback Award for Distinguished Teaching from the University of Pennsylvania this year.
Among the Academy’s Fellows are more than 250 Nobel laureates and 60 Pulitzer Prize winners. The new class will be inducted at a ceremony on October 10, 2015.
Chain of Life
An unprecedented kidney exchange involving 25 transplant centers and 70 patients began in late January with an altruistic donor at the University of Minnesota. It ended in late March when a kidney from Matt Crane was flown from the Hospital of the University of Pennsylvania to the final recipient waiting in Madison, Wis. In the meantime, Michele Crane, Matt’s wife, received a kidney from another perfectly matched stranger in New York. Like Matt, the last donor was not a match for his or her loved one. Paired exchanges are giving new hope to patients who are in need of a lifeline but do not have a match among their family or friends. The National Kidney Registry organized the national exchange.
Sixty-eight patients, 25 transplant centers, three months of surgeries, one massive kidney transplant chain. The lifesaving chain ended in March with two Penn patients after a New York donor’s kidney was delivered to a recipient at Penn, whose husband donated a healthy kidney to a recipient in Wisconsin.
Appointments
Donita Brady, Ph.D., was named the seventh Presidential Professor at the University of Pennsylvania, effective July 1. She will be Presidential Assistant Professor of Cancer Biology in the Perelman School of Medicine. Brady’s groundbreaking research studies the links between cancer and copper, with potential for the development of future cancer treatments. She and a team of Duke University researchers discovered that reducing the body’s supply of copper also blocks the growth of certain kinds of cancers – specifically, cancers with a mutation in the BRAF gene that require copper for the growth of cells and tumors.
This class of cancers includes melanoma, one of the most common and deadly forms of skin cancer, as well as colon, lung, and thyroid cancers. Brady’s research, which has been featured in first-author studies in such leading journals as Nature and Molecular and Cellular Biology, has significant implications for the production of new treatments, including the use of existing drugs for Wilson’s disease, a rare genetic disorder in which the body accumulates too much copper.
Brady had been a senior research associate in the Department of Pharmacology and Cancer Biology at the Duke University School of Medicine. She earned a doctorate in pharmacology in 2008 from the University of North Carolina at Chapel Hill.
Thomas P. Cappola, M.D., Sc.M., a physician-scientist with expertise in heart failure, was named chief of the Division of Cardiovascular Medicine and the Herbert C. Rorer Associate Professor of Medical Sciences. The division includes interventional cardiology, electrophysiology, heart failure and transplantation, adult congenital heart disease, consultative cardiology, noninvasive imaging, preventive cardiology and vascular medicine. It cares for more than 68,000 patients each year.
Since coming to Penn in 2003, Cappola has served as an attending cardiologist on Penn’s nationally recognized advanced heart failure and transplantation service. A former director of HUP’s Clinical and Translational Research Center, he was recognized in 2008 with a Presidential Early Career Award for Scientists and Engineers for applying genomic methodologies to identify the molecular and genetic basis of heart failure. He is co-principal investigator of the Mid-Atlantic Heart Failure Network, sponsored by the National Heart Lung and Blood Institute. A member of the American Society of Clinical Investigation, he is a fellow of the American Heart Association.
Emma Meagher, M.D., associate professor of medicine, was appointed senior associate dean and chief clinical research officer. This new leadership position was created to elevate Penn Medicine’s standing at the forefront of clinical and translational research and to enhance the conduct of clinical trials. The mission of the Office of Clinical Research is to standardize the approach to clinical research across the various research centers and departments in the Perelman School and to support investigative teams through regulatory and operational assistance as well as enhancements in study management and oversight. Meagher has served as executive chair of Penn Medicine’s Institutional Review Board, associate vice provost for human research, and associate dean for clinical research.
Meagher recently received the 2014 Alpha Omega Alpha Robert J. Glaser Distinguished Teacher Award. Among her cited achievements: redesigning the Perelman School’s formerly fragmented pharmacology curriculum and creating “Case Studies in Translational Research,” a course for M.D./Ph.D. students that explores the challenges and opportunities surrounding personalized (precision) medicine, diagnostics, and devices. Her teaching has also been recognized by the University of Pennsylvania, which honored her with the Lindback Award for Distinguished Teaching.
Turning the Pages of History
In the fall of 1765, two forward-looking physicians, John Morgan and William Shippen Jr., began lecturing at the first medical school in North America – part of what was then called the College of Philadelphia, forerunner of the University of Pennsylvania. Before that time, American physicians received their medical education as apprentices to practicing physicians and from scarce textbooks published in Europe. Those with means, including Morgan and Shippen, may have studied abroad. The University of Pennsylvania changed those paradigms and transformed medical education in this part of the world.
A limited-edition book, To Spread the Light of Knowledge, was published to mark 250 years of what is now known as the Perelman School of Medicine. Filled with never-before-compiled archival images, the book chronicles the fascinating history of the school, from its beginning as a few lectures given in borrowed space to the extensive curriculum, research, and multidisciplinary clinical practice within Penn Medicine today. To learn more about the 192-page, full-color book that celebrates this momentous milestone and to explore the book’s companion website and an interactive timeline, go to www.med.upenn.edu/psom250.
What’s New in Botswana?
The Botswana-UPenn Partnership (BUP), established in 2001, has continued to make significant progress in improving the health of the population of the African nation. One of the Partnership’s recent initiatives is the unforeseen result of interventions two decades ago: the introduction of antiretroviral drugs that considerably increased the life expectancies of people living with HIV. Many of them are women (now from 39 years to the low 60s) who were also infected with the human papilloma virus (HPV). As a result, this group of women is at a much higher risk of developing HPV-associated cervical cancer.
To better understand these co-infections and develop optimal prevention and therapeutic approaches, the Perelman School and the Botswana-UPenn Partnership will use a five-year, $3.5 million U54 grant from the National Cancer Institute (NCI). The NCI’s U54 program is an initiative developed to strengthen the capabilities of sub-Saharan African institutions by collaborating with partnering institutions or cancer centers. Collaborating investigators come from Penn’s departments of Microbiology, Radiation Oncology, Obstetrics & Gynecology, the division of Infectious Diseases, and the Annenberg School of Communication, as well as the University of Botswana.
The grant supports the continued efforts of Doreen Ramogola-Masire, M.D., country director of the Botswana-UPenn Partnership, in cervical cancer screening in Botswana, as well as the telemedicine efforts with mobile phones. In Philadelphia, the virology laboratory led by Erle S. Robertson, Ph.D., professor of microbiology, will sequence and analyze patient samples to study the viruses more closely. It will also identify other viral, bacterial, and parasitic agents that are involved in tumor formation.
Extending Reach Through Telemedicine
The Partnership is also collaborating with Microsoft, the Botswana Innovation Hub, and other global partners to launch the first telemedicine service in Africa. It will use TV “white spaces” technology to bring Internet connectivity to hospitals and clinics across rural areas of Botswana. The pilot project, called “Project Kgolagano,” will provide clinical consultations and diagnoses to a patient population that would otherwise have to travel far distances to the capital city of Gaborone for specialized care. Penn Medicine telemedicine experts and physicians, including Ramogola-Masire and Ryan Littman-Quinn, director of Mobile Health Informatics at BUP, will provide the support and medical expertise for the referred patients. Harvey M. Friedman, M.D., professor of medicine in the Division of Infectious Diseases at Penn and director of the Partnership, is the principal investigator of Project Kgolagano, which means to be connected or networked.
Through its 4Afrika initiative, Microsoft has launched similar pilots across Africa. Project Kgolagano will have a specific focus on providing access to specialized maternal medicine, which will improve the livelihoods of women located in small towns and rural areas.
This latest project builds upon the Partnership’s continuing telemedicine efforts with cell phone technology in the country. “People won’t have to travel hundreds of miles to the see specialists, which are lacking in many of the rural hospitals in the country,” said Friedman. “They will be able to engage with Penn Medicine doctors and residents who work over there from their local hospitals and clinics in a live telemedicine connection that will deliver care in a faster, more convenient, and cost-effective manner.”
Other collaborators on the project include Global Broadband Solutions, Vista Life Sciences, BoFiNet, Adaptrum, and USAID-NetHope.
– Steve Graff
On Uncertainty
I am a medical geneticist, and I have been struck by the irony that, as we are able to scrutinize our individual genetic codes in ever more precise ways, down to one nucleotide change out of 6.4 billion possibilities, we have more and more difficulty interpreting any given variation. This irony gives me and my genetic counselors considerable heartburn, but is typical of the health sciences today. . . . We faculty were expected to teach the truth and rid you of uncertainties. However, we are notorious for telling our first-year medical students that one-half of what we will teach will be viewed as incorrect in ten years; unfortunately, we just do not know which half.
—Reed Pyeritz, M.D., Ph.D., the William Smilow Professor of Medicine and Incoming Chair of the University’s Faculty Senate; delivered at the University Commencement, May 16, 2015.
Honors and Awards
Xianxin Hua, M.D., Ph.D., a professor of cancer biology, was named one of 11 recipients of a Harrington Scholar-Innovator Award. Presented by the Harrington Discovery Institute at University Hospitals in Cleveland, the awards support drug discovery efforts of great promise. Hua’s award is for $100,000 over two years. According to Hua, the award will serve as a catalyst to accelerate transition from his laboratory’s basic biomedical research “to develop a novel modality to treat diabetes, by tapping diabetes patients’ own ability to regenerate beta cells.”
Hua’s lab looks at a protein called menin and how it regulates the expression of genes and growth of certain types of cancer cells and endocrine cells such as insulin-secreting beta cells. Menin works by physically interacting with other partner proteins, and these protein complexes then bind to the promoter of various specific genes, ultimately modulating a beta cell’s capability to regenerate.
The Scholar-Innovators also are given access to Harrington’s Innovation Support Center, which includes a renowned group of industry experts charged with helping guide drug development. Successful initiatives have access to several rounds of capital support to commercialize their basic discoveries.
Carl June, M.D., an expert in cancer and HIV, has continued to accrue honors this year. He is the Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine and director of Translational Research in Penn’s Abramson Cancer Center. June is widely recognized as leader of the team responsible for the first successful and sustained demonstration of the use of CAR T cell therapy, an investigational approach in which a patient’s cells are removed through an apheresis process similar to dialysis and modified in Penn’s cell and vaccine production facility. Scientists there reprogram the patients’ T cells through a gene modification technique using a viral vector that trains them to recognize specific types of cancer cells. The modified cells – known as chimeric antigen receptor (CAR) T cells – are then infused back into the patient’s body, where they multiply, hunt and attack tumor cells.
June was named one of two recipients of the 2015 Paul Ehr-lich and Ludwig Darmstaedter Prize for his outstanding work in cancer immunotherapy. Since 1952, the prize has been awarded to scientists who have made great advancements in the fields in which Paul Ehrlich worked, in particular immunology, cancer research, microbiology, and chemotherapy. June also received the Lloyd J. Old Award in Cancer Immunology, presented by the American Association for Cancer Research at this year’s annual meeting. He is a senior editor of the Association’s journal, Cancer Immunology Research. In addition, Pennsylvania Bio, the statewide bioscience trade organization, honored June with its 2015 Hubert J. P. Schoemaker Leadership Award. It is presented to a Pennsylvania scientist who has shown a “spirit of innovation” throughout his or her career. Last year, June was elected to the American Academy of Arts and Sciences.
Robert L. Mauck, Ph.D., an associate professor of orthopaedic surgery, is one of four scientists given awards by the Kappa Delta Sorority and the Orthopaedic Research and Education Foundation at the 2015 Annual Meeting of the American Academy of Orthopaedic Surgeons. Awardees are chosen for their outstanding basic
science and clinical research related to musculoskeletal disease or injury, with the ultimate goal of advancing patient treatment and care. Each award carries a $20,000 stipend.
Mauck received the 2015 Kappa Delta Young Investigator Award for his research on developing and optimizing nanofibrous scaffolds – extremely small, bioengineered materials – to repair or replace complex connective tissues, such as those that make up the meniscus of the knee joint or the intervertebral disc of the spinal column.
Complex connective tissues do not heal well, primarily because of their dense makeup with few cells and blood vessels. The challenge, says Mauck, a researcher at the McKay Orthopaedic Research Laboratory, is to find or create a regenerative treatment to restore the fiber arrangement of the tissue and the mechanical integrity of the structure. He and his team used a process called electrospinning to produce the nanofibrous, mesh scaffolding. This process uses a variety of synthetic and natural polymers to provide an organized healing framework for cell recruitment and tissue formation in damaged areas.
The laboratory of David Weiner, Ph.D., a professor of pathology and laboratory medicine, received the 2015 Vaccine Industry Excellence Award for Best Academic Research Team at the World Vaccine Congress in Washington, D.C. The Congress is an annual meeting of vaccine professionals from industry, academia, and non-profit organizations.
The Weiner lab’s DNA vaccines program was chosen over other finalists from Duke University, Harvard Medical School, and the Memorial Sloan-Kettering Cancer Center by hundreds of vaccine stakeholders who voted for those most deserving of recognition for their work across 14 vaccine-related categories.
The award is given annually to the research group that has produced products with a novel mode of action, seen them progress into human trials, and can demonstrate significant supportive research grants.
Weiner is also chair of the Gene Therapy and Vaccine Program and co-leader of Tumor Virology Program in the Abramson Cancer Center.
James M. Wilson, M.D., Ph.D., professor of pathology and laboratory medicine, received the 2015 Scientific Achievement Award, presented by Pennsylvania Bio, the statewide bioscience trade organization. It honors a Pennsylvania scientist who has advanced scientific knowledge, innovation, and/or patient care. From the earliest days of work with gene therapy in the 1980s, Wilson’s research focus has been rare inherited diseases, ranging from cystic fibrosis to dyslipidemias to a variety of metabolic disorders. Most recently, Wilson’s laboratory discovered a family of viruses from primates that could be engineered to be very effective vehicles for transferring genes. These “vectors” have become the technology platform of choice and have helped set the stage for the recent resurgence of the field of gene therapy. Since joining Penn Medicine in 1993, Wilson has received more than 90 patents. He directs Penn’s Orphan Disease Center and the Gene Therapy Program.
Letters
More on the Penn-Burma Connection
The feature “From Burma to Penn: A Family Saga” in the recent Spring issue of Penn Medicine was very interesting. There were, in fact, several doctors and a nurse who came from Burma to Penn prior to 1970 thanks to Professor Ravdin. Ruby Thaw, a Burmese nurse who had also been with Dr. Gordon Seagrave, the Burma surgeon, was in the OR with Dr. Ravdin at the 20th General Hospital and was the first to come to HUP. Although the hospital was in Assam [India], Drs. Julian Johnson, Cletus Schwegman, and Ravdin traveled into northern Burma as far as Myitkyina.
Sometime near the end of the war in 1945, Dr. Ravdin was in Rangoon and met Dr. Ba Than, Professor of Surgery and Dean of Rangoon University Faculty of Medicine. Dr. Ba Than had refused to leave the country during the Japanese occupation even when the university was closed and Rangoon was being bombed regularly, especially on Sunday mornings. It may have been forgotten, but after the war tentative plans were in progress between Penn and the Rangoon University Faculty of Medicine for an exchange program intended to upgrade Rangoon U, which had been stripped by the Japanese. All of the equipment, books, and supplies were sent back to Japan, including the bronze statue of Sir Spencer Harcourt Butler, a former British Governor of Burma.
The negotiations were suddenly and abruptly called off by the Burmese government for reasons which were probably covertly political. However, from 1954 to 1959 the first group of Rangoon University Medical graduates came to HUP for residency training programs: Dr. San Baw (Orthopaedics), Dr. Aung Than (Dentistry and Plastic Surgery), Dr. Myint Myint Khin (Medicine), Dr. Saw Nyun (Neurosurgery), Dr. Albert Ai Lun, a protégé of Dr. Seagrave (Surgery), and me, Simon Kyaw Myint (Surgery). Although born and brought up in Burma, I am a graduate of Northwestern University School of Medicine.
Dr. Kyee Paw (Surgery) and Dr. Ronald Lwin (Cardiology) came to HUP for short-term visits. Sent by the U.S. State Department, both were on the faculty of Rangoon University.
There was a hiatus after this group, and then a few more came along. I might add that I am the only one left of the first group and at 87 am still able to do volunteer work as a surgeon at a remote hospital in Nepal.
—Simon Kyaw Myint, M.D., G.M.E. ’66, Diplomate American Board of Surgery, American Board of Thoracic Surgery
Another Look at Gurin and Gellhorn
A splendid issue of Penn Medicine Spring 2015 and a discerning article on deans (“A Pair of Visionary Deans”).
I knew both Sam and Alfred. Sam Gurin tried to teach me biochemistry and was one of the basic science trio, with Dale Coman and Lew Flexner, who wrenched control from the HUP clinicians. I did not know he was almost a professional pianist, like Hilary Koprowski, but a lovely man. Alfred Gellhorn was ahead of his time, for Penn certainly, supplied us with pregnant sheep and hated to be recognized as Hemingway’s brother-in-law. He was anathema to some HUP clinicians and much of what he did was taken down after he left. But two steps forward and one back.
—Robert Forster, M.D. ’43 D
Editor’s Note: Dr. Forster, the Isaac Ott Emeritus Professor of Physiology and former chair of the Department of Physiology, received the School of Medicine’s Distinguished Graduate Award in 1995.