Alumni and Student Programs

Peter M. Howley, MMS ’70, MD:
How Idealism, Curiosity, and a Critical Mind Led to a Major Scientific Discovery

One of the medical school’s earliest graduates is among its most accomplished. Peter M. Howley, MMS ’70, MD, Shattuck Professor of Pathological Anatomy and chair, Department of Pathology, Harvard Medical School, went to lectures in temporary Quonset-hut classrooms at what was then named Rutgers Medical School (RMS). He saw the Research Tower completed just in time for his Commencement.

Dr. Howley has remained dedicated to finding clinical applications for his science, starting with his early training in the rudiments of medical research, under Joel Kirkpatrick, MD, assistant professor of pharmacology and pathology, and continuing up to a landmark discovery last year made possible by proteomics.

In 1968, the medical school in Piscataway was an “exciting new experiment,” recalls Dr. Howley. Its founding dean, DeWitt Stetten, MD, PhD, was a renowned physician-scientist who recruited an extraordinary faculty, which in turn would attract first-rate students. “We were aware of the exceptional opportunities the school would offer,” Dr. Howley says.

Victor Stollar, MD, professor of molecular genetics, microbiology, and immunology, was one of the medical school’s first faculty members. “We were young and idealistic,” says Dr. Stollar, “and we seemed to appeal to a certain type of student — of which Peter was certainly one. They could have been admitted anywhere, but they had an adventurous spirit that led them to take a risk on a young school. Peter was one of the best,” he adds, “and, throughout a remarkable career, he has remained as warm and approachable as he was at the time.”

Dr. Howley and Jianxin You, PhD, one of his post-doctoral fellows, examine the results of a virus inhibition assay in his laboratory at Harvard Medical School.

For Dr. Howley, an organic chemistry major at Princeton University, the world-class teaching at RMS and the school’s intense two-year master of medical science (MMS) program offered an ideal training ground in basic science research. He recalls the excellent courses and research opportunities, along with an early fascination with both the problem-solving aspects of pathology and the research opportunities in virology.

Along with one-quarter of his 16 RMS classmates, Dr. Howley went on to earn a medical degree at Harvard Medical School. He then completed an internship in pathology at Massachusetts General Hospital. In 1973, he received a highly competitive two-year commission in the U.S. Public Health Service (USPHS), where he fulfilled his draft obligations as a member of the elite “yellow beret” corps of physician-scientists. As a research associate, he was assigned to the National Institutes of Health (NIH) Laboratory of the Biology of Virology, opening the door to a career focused on viruses, both as tools to probe cellular processes and as causes of disease.

Dr. Howley’s two-year research associateship at the NIH would stretch to two decades. By the late 1970s, he had homed in on papillomaviruses, which not only cause diseases ranging from benign warts to potentially deadly cervical cancer, but also have idiosyncratic replication processes that are useful in the study of transcription and DNA replication. At the National Cancer Institute (NCI), he completed his training in anatomic pathology and became a principal investigator in its Laboratory of Pathology in 1977. In 1984, Dr. Howley was made chief of the Laboratory of Tumor Virus Biology at the NCI, a position he held until 1993, when he accepted an appointment at Harvard Medical School as George Fabyan Professor and chair, Department of Pathology.

Dr. Howley’s laboratory focuses on the molecular biology of the papilloma-viruses and their role in human cancer. Like peeling away the layers of an onion, Dr. Howley and his team have disclosed the molecular details of human papillomavirus (HPV) replication and discovered how it causes disease. Evolving knowledge about molecular biology and the development of the technology to manipulate and observe cell processes have provided the means to dissect the pathogenic mechanisms encoded by the HPVs. They also have helped to pinpoint the genes targeted by HPVs in the first step of carcinogenesis. “First the electron micrograph was there,” says Dr. Howley. “Later, with the sequencing of the human genome, we had an increasing ability to ask and answer questions about viruses and cancer. Today, we use chemical screening and proteomics to dissect pathways genetically and biochemically.”

Last year, studying the bovine papillomavirus (BPV), Jianxin You, PhD, a research fellow in Dr. Howley’s laboratory, made a landmark discovery about HPVs. “It definitely was an ‘a-ha’ moment for us,” recalls Dr. Howley. Using proteomic techniques, Dr. You identified BRD4, a cell protein that is targeted by the viral E2 protein. When BRD4 binds to E2, they found, it becomes the first domino in a sequence that leads to disease. By blocking the tethering of BRD4 and E2, the research team observed, they prevented the papillomavirus-infected cell from becoming cancerous. The discovery was published in the journal Cell in April 2004.

“This finding suggests that if one could come up with a small molecule or chemical that could inhibit the binding of E2 to BRD4, that could be a drug lead,” says Dr. Howley, who is now working with members of the Harvard University Department of Chemistry to identify such molecules.

Beyond the world of cells and viruses and departmental and professional responsibilities, Dr. Howley enjoys concerts by the Boston Symphony Orchestra as well as downhill skiing, fishing, and exploring the lakes and coast of Maine. He is particularly proud of his family, which, in addition to his wife, Ann, includes three daughters, one of whom recently completed graduate studies in molecular biology at Princeton University, and two black standard poodles.

Dr. Howley is widely recognized for his research achievements and holds nine patents for his work. A past editor and current editorial board member of the Journal of Virology, he also sits on the editorial boards of the Proceedings of the National Academy of Sciences, Molecular and Cellular Biology, and Laboratory Investigation. Dr. Howley’s awards include the Warner-Lambert/ Parke Davis Award (1983), Wallace P. Rowe Award (1986), UMDNJ Distinguished Alumnus Award (1986), USPHS Meritorious Service Award (1989), Paul Ehrlich Prize (1994), and the Rous-Whipple Award (2004). He is a member of the National Academy of Sciences, the Institute of Medicine, and the American Academy of Arts and Sciences, and is past president of the American Society for Virology. As a member of the scientific advisory board of The Cancer Institute of New Jersey (CINJ), Dr. Howley contributes to the UMDNJ-Robert Wood Johnson Medical School missions in research, education, and clinical care.

In addition to appreciating his ongoing connection to RWJMS through CINJ, Dr. Howley notes career-spanning personal links to the medical school. Arnold B. Rabson, MD, professor of molecular genetics, microbiology, and immunology and deputy director, CINJ, was a colleague and fellow researcher at the NIH. Dr. Howley has also co-authored papers on the p53 protein with Arnold J. Levine, PhD, professor of pediatrics and member, CINJ.

Summarizing his career, Dr. Howley says, “Once you learn to ask questions and think critically, you’re always learning new things.” In its simplicity, Dr. Howley’s statement encapsulates the intelligence that focuses his passion for science and impels him to create medical solutions from his discoveries.