A Pivotal Milestone in Cancer Treatment
In a landmark decision this August, for the first time, the U.S. Food and Drug Administration (FDA) approved a personalized cellular therapy for cancer; it is also the first FDA-approved therapy based on gene transfer. Developed by the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP), the chimeric antigen receptor (CAR) T-cell therapy will be sold by Novartis as Kymriah™ (tisagenlecleucel, formerly CTL019). The approval was granted for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia that is refractory or in second or later relapse. In 2012, Penn and Novartis entered into a global collaboration to further research, develop and commercialize Kymriah and other CAR-T cell therapies for the treatment of cancers.
“I think the cancer world is forever changed.”
– Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center, in the New York Times.
Investigators hailed the FDA’s approval as a game changer for the treatment of younger patients battling the aggressive blood cancer and a pivotal milestone in this new era of cellular therapies that treat cancer with a patient’s own immune system.
A more in-depth look at the path toward this milestone and the future beyond it will appear in the next issue of Penn Medicine. For a look at the role of philanthropy in this achievement, see Development Matters.
A Stethoscope, an Oath, and a Short White Coat
At the annual White Coat ceremony this August, 159 entering students received their first stethoscopes, recited the Hippocratic Oath, and donned their first short white coats. A bright and diverse group of medical students joined the ranks of the Perelman School of Medicine.
The school’s oldest living alumnus, Joseph Schein, MD’41, like all physicians in attendance, stood with the entering class to recite the oath. Schein attended in support of his granddaughter, Yvette Schein, as she began her medical training.
A Solid Foundation
When completed in 2021, Penn Medicine’s new inpatient facility, the Pavilion, will be a massive 1.5-billion square-foot facility with 500 private patient rooms and 47 operating rooms. It is already setting records and sitting on a solid foundation. Specifically, Penn Medicine set a Philadelphia construction record with a continuous pour of concrete over 14 hours for the Pavilion’s construction at its site across the street from the Hospital of the University of Pennsylvania. The 6,540 cubic yards of concrete required 654 concrete trucks and the work of more than 120 construction crew members, site managers, and safety support personnel.
Watch a time-lapse video of the concrete pour:
For the fourth year in a row, Penn Medicine hospitals ranked among the top 10 hospitals in the nation according to U.S. News & World Report. In its 2017-2018 annual survey, the magazine ranked the combined enterprise of the Hospital of the University of Pennsylvania (HUP) and Penn Presbyterian Medical Center (PPMC) as the 10th best hospital in the United States and as the No. 1 hospital in Pennsylvania, with additional top rankings in 11 clinical specialties. Of nearly 5,000 hospitals ranked, only 20 were selected for the Honor Roll, HUP/PPMC among them. Complete rankings as well as the U.S. News & World Report methodology can be found at www.usnews.com/besthospitals.
Honors & Awards
Jill M. Baren, MD, MBE’06
Professor, Emergency Medicine
John Marx Leadership Award
A renowned expert in emergency clinical trials, informed consent, and neurologic emergencies, Baren was recognized by the Society for Academic Emergency Medicine for exceptional contributions to emergency medicine through leadership.
David F. Dinges, PhD
Professor, Psychiatry; Chief, Sleep and Chronobiology
Nathaniel Kleitman Distinguished Service Award
The award from the American Academy of Sleep Medicine recognizes individuals dedicated to the sleep field who have made significant contributions in the areas of administration, public relations and government affairs.
Ronny Drapkin, MD, PhD
Associate Professor, Pathology in Obstetrics & Gynecology; Director, Ovarian Cancer Research Center
Rosalind Franklin Prize for Excellence in Ovarian Cancer Research
The prestigious award is from the Ovarian Cancer Research Fund Alliance in recognition of an individual’s contributions to basic science, translational, or clinical research in ovarian cancer.
Ronald M. Fairman, MD, GME’84
Clyde F. Barker-William Maul Measey Professor, Surgery; Professor, Radiology; Chief, Vascular Surgery and Endovascular Therapy
Chair, Society for Vascular Surgery Foundation
Fairman served as the foundation’s president last year. As chair, he will manage its highly competitive, peer-reviewed grant initiatives.
Irene Hurford, MD
Assistant Professor, Psychiatry
2017 Exemplary Psychiatrist Award
The National Alliance on Mental Illness honored Hurford for work that helps people at early stages of psychosis to manage their symptoms and achieve life goals, emphasizing recovery and resilience.
Carl June, MD
Richard W. Vague Professor, Pathology and Laboratory Medicine; Director, Center for Cellular Immunotherapy and Parker Institute for Cancer Immunotherapy
David A. Karnofsky Memorial Award
This honor from the American Society of Clinical Oncology goes to an oncologist who has made outstanding contributions to cancer research, diagnosis, and treatment.
Francis Marchlinski, MD’76, GME’81
Richard T. and Angela Clark President’s Distinguished Professor of Medicine; Director, Electrophysiology
Heart Rhythm Society Distinguished Teacher Award
The international society recognized Marchlinski for educating colleagues and students for over 30 years, including providing vital information about his own clinical innovations in therapies for heart failure, atrial fibrillation, and ventricular tachycardia.
Emma A. Meagher, MD
Associate Professor, Medicine and Pharmacology; Vice Dean and Chief Clinical Research Officer; Senior Associate Vice Provost for Human Research
President, Association for Clinical and Translational Science (ACTS)
With a mission to advance research and education in clinical and translational science in order to improve human health, ACTS comprises 5,000 clinicians and researchers from 50 universities and medical centers nationwide.
Angela M. Mills, MD, GME'03
Associate Professor, Emergency Medicine
Arnold P. Gold Foundation Humanism in Medicine Award
Honored for compassionate, patient-centered care, by the Society for Academic Emergency Medicine, Mills serves as clinical mission leader for Emergency Medicine as the department’s vice chair for clinical operations.
Jason H. Moore, PhD
Edward Rose Professor, Informatics; Director, Institute for Biomedical Informatics
Fellow, American Statistical Association
Moore’s research focuses on developing and applying artificial intelligence and machine learning methods for uncovering complex patterns in biomedical big data.
Benjamin L. Prosser, PhD
Assistant Professor, Physiology
Outstanding Early Career Investigator Award
The American Heart Association’s Council on Basic Cardiovascular Sciences recognized Prosser for his research to date and a heart-failure discovery to improve the beating strength of heart cells by “softening” their internal cytoskeleton.
Ilene Rosen, MD’93, MSCE’06
Professor, Clinical Medicine
President, American Academy of Sleep Medicine (AASM)
Rosen plans to help AASM members advance patient care and quality of life at a time when understanding of the role of sleep in care of cancer, neurological disorders, and more, is expanding.
Anil K. Rustgi, MD
Professor and Chief, Gastroenterology
2017 Julius Friedenwald Medal
This American Gastroenterological Association’s highest lifetime honor recognizes contributions to all aspects of gastroenterology, including research, clinical medicine, education and service.
Felix W. Wehrli, PhD
Professor, Radiology
Gold Medal Award
The Society for Magnetic Resonance in Medicine honored Wehrli, whose research focuses on the conception, implementation and translation to the clinic of new quantitative imaging methods by MRI.
Penn Medicine has been named No. 7 on Forbes magazine’s annual “Best Employers in America” list ranking mid-sized and large employers across the U.S. Other organizations listed in the top ten include Costco, Google, and REI, placing Penn Medicine among some of the most well-known and influential companies in the nation.
“We are extremely proud of the exceptional care we offer our patients, which is sustained by the commitment, compassion, and talent exhibited by every single person who works at Penn Medicine,” said Ralph W. Muller, CEO of the University of Pennsylvania Health System. “Our staff is our greatest asset as we work together to continue our efforts as a health care leader.”
Forbes partnered with research firm Statista, of Hamburg, Germany, to build its list of best employers. Statista’s survey of 30,000 U.S. workers, asking them if they would recommend their organization to friends or family, was the most heavily weighted factor in determining the list.
The full list of Forbes’ “Best Employers in America” is available at Forbes.com/best-employers.
The Perelman School of Medicine will establish the Asperger Syndrome Program of Excellence (ASPE) with a $5.4 million gift from an anonymous donor. Led by Daniel J. Rader, MD, chair of Genetics, ASPE aims to energize the international research and clinical community by improving understanding of the genetic causes of Asperger syndrome (defined as autism spectrum disorder without intellectual disability). ASPE will take a two-pronged approach by conducting a pioneering family-based genetic study and simultaneously developing model systems to investigate specific mutations in genes found in earlier genome-wide association studies of autism spectrum disorders. Penn will host an international symposium for ASPE in the spring of 2018 to review early findings and stimulate new research avenues.
A Familiar Face Among Penn’s Newest PIK Professors
Risa Lavizzo-Mourey, MD, MBA’86, returns to Penn’s faculty Jan. 1, 2018 as the Robert Wood Johnson Foundation Population Health and Health Equity Professor with joint appointments in Medical Ethics and Health Policy in the Perelman School of Medicine, in Health Care Management in the Wharton School and in Family and Community Health in the School of Nursing. A world-renowned expert in health policy and geriatric medicine, Lavizzo-Mourey has served since 2003 as president and chief executive officer of the Robert Wood Johnson Foundation, and, for 15 years before that, as a distinguished professor and administrator at Penn.
Lavizzo-Mourey’s new appointment will be as a Penn Integrates Knowledge (PIK) University Professor. PIK professorships are University-wide initiative to recruit exceptional faculty members whose research and teaching exemplify the integration of knowledge across disciplines and who are appointed in at least two schools at Penn.
Two new PIK Professors joined Penn Medicine in July. Jay Gottfried, MD, PhD, GME’01, a pioneer in research on the neuroscience of the sense of smell, is the Arthur H. Rubenstein University Professor, with joint faculty appointments in Neurology in the Perelman School of Medicine and in Psychology in the School of Arts and Sciences. Get to know computational neuroscientist Konrad Kording, PhD, in a feature story in this issue, Level Up: Neuroscience. In September, George Demiris, PhD, a leader in new technologies for e-health and home-based health care, was announced as the next new PIK Professor appointment; he will join Penn Medicine and Penn Nursing in 2018.
Mixing Metaphors and Methods
Highlights of recent Penn Medicine research, from innovations in hard-to-treat cancers to uncovering mysteries of the teenage brain
Retracing the Steps of Pancreatic Cancer Development Yields Early-Detection Blood Test
Researchers retraced the steps of how cells develop into pancreatic cancer and identified a signature footprint that could help diagnose this deadly cancer in an earlier stage. The team from Penn Medicine and the Mayo Clinic used a first-of-its-kind human-cell model of pancreatic cancer progression, initially described in 2013, for this study in which they genetically reprogrammed late-stage cancer cells into a stem-cell state. This enabled them to force the reprogrammed cells to progress to an early cancerous state, revealing secreted blood biomarkers of early-stage disease along the way. The findings were published in Science Translational Medicine. The researchers anticipate that health care providers will test for the presence and levels of these biomarkers in blood from pancreatic cancer patients and individuals with a high risk of developing pancreatic cancer.
Fuel for the Molecular Machinery of Memory
A metabolic enzyme “fuels” the machinery that controls which genes are expressed in the coordinated process of creating a memory, according to Penn Medicine research published in Nature. Forming memories involves restructuring of the synapse (the space between neurons), and that process relies on the coordinated expression of a group of memory genes. The addition of a chemical group, a process called acetylation, onto specific spots of the genome in neurons, opens up tightly-wound DNA to make genes involved in memory formation available to be “read,” and eventually, for their encoded proteins to be made. The Penn researchers reported that a key metabolic enzyme, called acetyl-CoA synthetase 2, or ACSS2, works directly within the nucleus of neurons to turn genes on or off when new memories are being established. It binds to memory genes to directly regulate and fuel their acetylation, which is ultimately controlling spatial memory in mice. The researchers hope to apply this newfound memory path to prevent or even erase traumatic memories in people who suffer from post-traumatic stress disorder, by blocking ACSS2 in the hippocampus, a brain region that processes long-term memory.
A Clarion Call for the Immune System to Fight Cancer
A clarion call that summons the immune system to deal a final blow to damaged cancer cells originates with surveillance proteins inside of those cells, according to Penn Medicine research published in Nature. These surveillance proteins typically detect foreign DNA from invaders such as viruses, but after DNA damage from cancer treatments such as chemotherapy and radiation, they can also find exposed DNA from the cell itself after pieces of it break off into micronuclei that are prone to rupture. The surveillance proteins then incite an immune response. Describing this mechanism helps to explain why immune cells arrive at tumors days after chemotherapy and radiation and not right away. The Penn team also found that this delay is the result of the tumor cells’ progress through cell division; they conclude that changes in how fast or slow a cancer cell divides are an important consideration for cancer therapies that combine DNA damage and immune checkpoint inhibitors.
A Ratchet Mechanism Untangles Distorted Proteins
The digital animation looks a bit like a sea creature climbing a rope. What it really shows is how a tangle-busting enzyme called Hsp104 processes a protein strand, stepwise in one direction, like a ratchet, with the enzyme’s six subunits latching to the strand in sequence as it is pulled through the enzyme’s central channel. The strand ultimately gets pulled out of the aggregate of a tangle of protein fibrils and can refold or be degraded. Researchers are interested in the therapeutic potential of this mechanism because misfolded proteins are the culprits behind amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, and other neurodegenerative brain disorders. These distorted proteins are unable to perform their normal functions and clump together, causing devastating problems, and currently, there is no way to untangle the knotted mass of these proteins to treat disease. Hsp104 (heat shock protein 104), found in yeast, has been studied for its tangle-busting qualities for years. Researchers from Penn Medicine and the University of Michigan published the new study in Science; their up-close view of how Hsp104 works can enable better engineered molecules that could be used as therapeutics for neurodegenerative diseases.
Modules Mark Maturity in Adolescent Brains
Distinct parts, called modules, in the brain, emerge during adolescence as part of a maturation process during which the brain also becomes more globally integrated, according to a study by University of Pennsylvania researchers, published in Current Biology. Modules are parts of a network that are tightly connected to each other, and less connected to other parts of the network. Modules are thought to support specialized brain functions like movement, sensation, vision, and more complicated tasks like executive function (the ability to control impulses, stay organized, and make decisions). The new evidence shows that the degree to which executive function develops during adolescence and young adulthood, depends in part on the degree to which these modules are present. The findings could lead to the identification of biomarkers of abnormal brain development that could predict a person’s risk for psychosis and major mood disorders.
An Electric Pulse with DNA Vaccine for HPV-Related Head and Neck Cancer
Physicians used a special device to deliver a pulse of electricity to the area where antigens were injected in an effort to activate an immune response to human papillomavirus (HPV) subtype 16/18. The pulse stimulates the muscles and speeds the intake of the antigens. Penn Medicine researchers presenting at American Society of Clinical Oncology Annual Meeting this year reported success with this DNA-based vaccine delivered to patients who had already undergone therapy that was intended to be curative for head and neck cancer. HPV is an increasingly common cause of head and neck cancers—accounting for an estimated 70 percent of cases today. And 60 percent of cases are caused by the subtype HPV 16/18. When doctors followed up an average of 16 months after the DNA vaccine, 18 of the 22 patients showed elevated T cell activity that was specific to HPV 16/18. A multi-site trial is planned to test the vaccine in combination with drugs for patients with metastatic cancer.
Glowing Tumors Aid Precision Surgery
Making tumor cells glow from an injected, near-infrared contrast dye, is a bright idea in precision surgery. Penn researchers continue to publish surgical milestones from the use of this method, called intraoperative molecular imaging (IMI). One team from the Abramson Cancer Center, which published in Annals of Surgery, was able to identify and remove a greater number of cancerous nodules from 50 lung cancer patients when combining IMI with preoperative positron emission tomography (PET) scans. It was the first study to show the effectiveness of combining the techniques. A separate pilot study with 15 neurosurgery patients showed that IMI successfully lit up the benign brain tumors known as pituitary adenomas during removal surgery, allowing surgeons to identify tumor tissue. These tumors are the third most common brain tumor and can cause blindness and hormonal disorders. Over the past four years, Penn surgeons have performed more than 400 procedures using both nonspecific and targeted near infrared dyes in tumor types including lung, brain, bladder and breast.