Lewis A. Chodosh, MD, PhD

2012-2013 BCRF Project:
Dr. Chodosh's laboratory has developed a unique set of genetically engineered laboratory models of breast cancer in order to understand the mechanisms by which developmental events modulate breast cancer risk. They have also investigated the biology of estrogen receptor positive (ER+) breast cancers that were caused by oncogenic pathways. During the past year, Dr. Chodosh's team has identified an unexpected role for the hormone, prolactin, in breast tissue. These models and observations have enabled the testing of a first-in-class pharmaceutical agent in collaboration with a major pharmaceutical partner that targets a critical hormonal pathway. In the coming year, the researchers will build on these efforts to understand these effects at a molecular and a cellular level and to determine how to leverage these findings to develop better treatments for breast cancer.

In addition, Dr. Chodosh's projects seek to understand the role played by prolactin in mammary development and tumor formation. They also aim to develop computational methods to select appropriate targeted therapies for patients, and investigate the genetic basis for mammographic density and its relationship to breast cancer risk.

Mid-year Progress: The hormone prolactin, which is normally produced by the pituitary gland, is a central regulator of the normal development of the breast. Recent studies have shown that prolactin is also synthesized in breast epithelial cells and in some human breast cancers, but the regulation of its production and its functional significance are unknown. In studies supported by the BCRF, Dr. Chodosh and his team have discovered that production of prolactin in the breast is controlled by the PI3K-Akt signaling pathway, which is one of the most commonly activated oncogenic pathways in human breast cancers, and that prolactin produced by the breast is required for the proper onset of lactation in mice. Their findings thus far have provided the first demonstration of what regulates prolactin synthesis in the breast, identify a physiological function for prolactin produced in the breast, and reveal a direct connection between the production of prolactin and pathways known to be involved in the pathogenesis of human breast cancer. Their study raises the possibility that prolactin produced by the breast may play a role in breast cancer development, which in turn has intriguing potential implications for the treatment of breast cancer patients. Further investigation will be required to determine whether therapeutic approaches aimed at blocking prolactin action in the breast will be beneficial in the treatment of breast cancer patients.

Bio:
Dr. Lewis Chodosh joined the faculty of the University of Pennsylvania School of Medicine in 1994 and currently serves as Chairman of the Department of Cancer Biology. Dr. Chodosh holds appointments as an Professor with Tenure in the Departments of Cancer Biology, Cell & Developmental Biology, and Medicine in the Division of Endocrinology, Diabetes and Metabolism. In addition, Dr. Chodosh is an Investigator of the Abramson Family Cancer Research Institute. As a physician-scientist, Dr. Chodosh is principally dedicated to leading a research laboratory of 23 graduate students, technologists and postdoctoral fellows in a comprehensive research program aimed at eradicating breast cancer.

Dr. Chodosh's scientific career is founded on academic achievement. He graduated summa cum laude, Phi Beta Kappa from Yale University in 1981 with Distinction in Molecular Biophysics and Biochemistry. In 1989, Dr. Chodosh simultaneously received his M.D. from Harvard Medical School, where he graduated magna cum laude, and his Ph.D. in Biochemistry at the Massachusetts Institute of Technology under the mentorship of Nobel laureate, Dr. Phillip Sharp. After a residency program in Internal Medicine at the Massachusetts General Hospital, Dr. Chodosh completed a clinical fellowship in Endocrinology at the Massachusetts General Hospital in 1992 and a postdoctoral research fellowship with Dr. Philip Leder at Harvard Medical School in 1994.

As a clinical and scientific trainee, Dr. Chodosh has received numerous honors including the Leon Reznick Memorial Prize for Excellence in Research from Harvard Medical School, the Emerson Tuttle Cup for Distinguished Academic Achievement from Yale University, the Cornell Ingenuity in Mathematics and Science Award, the Harvard Book Prize, the Bausch and Lomb Honorary Science Award, the Merck Research Laboratories MD/PhD Fellowship, the Charles E. Culpeper Foundation Scholarship in Medical Science, and the AACR-Sidney Kimmel Cancer Symposium for Cancer Research Scholar Award. Dr. Chodosh was elected to the American Society for Clinical Investigation in 2002.

As an independent investigator at the University of Pennsylvania, Dr. Chodosh has focused his clinical and research training on developing new experimental approaches to understanding, treating and preventing breast cancer. Dr. Chodosh is particularly interested in identifying the mechanisms by which human cancers become resistant to therapy, as well as in understanding how normal events in a woman's life can be protective against breast cancer. In pursuit of these goals, Dr. Chodosh's laboratory has developed several novel genetically engineered mouse models for breast cancer, as well as a number of innovative approaches to analyzing large microarray gene expression profiling data sets.

In addition, Dr. Chodosh serves as an Attending Physician on the Endocrine Consult Service at Hospital of the University of Pennsylvania. Dr. Chodosh also serves as an advisor to the Harvard Nurses Health Study, is the senior editor of the scientific journals Breast Cancer Research and an editor of Cancer Biology and Treatment, and is on the Editorial Board of the Journal of Mammary Biology and Neoplasia.