Marc E. Lippman, MD
Kathleen & Stanley Glaser Professor; Chairman, Department of Medicine
Miller School of Medicine, University of Miami, Miami, FL
2009-2010 BCRF Project:
(made possible by generous support from Play For P.I.N.K.)
The over arching goal of this project is to investigate the mechanism by which estrogen (E2) regulates breast cancer growth by identifying novel genes involved in the process and then targeting them therapeutically. Validation of these genes will assist in identifying the patients who will benefit from endocrine therapy and result in reduced mortality for breast cancer patients. GREB1, regulated by estrogen in breast cancer cells and originally isolated by Ghosh MG et al, has been identified as a gene significantly changed by E2 stimulation among three breast cancer cell lines, MCF-7, T47D and BT-474 by a novel bioinformatics technique. In order to further study the role of GREB1 in breast cancer, Dr. Lippman and colleagues generated monoclonal antibodies to GREB1. They have validated the specificity of a monoclonal antibody against GREB1 and have investigated the ability of GREB1 to act as a surrogate marker for estrogen receptor and as a clinical biomarker by detecting GREB1 expression in breast cancer cell lines and tissues. They inserted the full-length cDNA of GREB1 into an adenovirus expression system and detected phenotypic changes in breast cancer cells. Finally, they constructed a GREB1-targeting vector with the aim of elucidating GREB1 function in mammary gland development in vivo by knocking out the GREB1 gene in laboratory models.
For the coming grant period, the researchers plan to build on their new insights and employ novel models to focus their efforts on elucidating the function of GREB1 in breast cancers leading to the development of new therapeutics as well as the identification of additional targets involved in estrogen stimulated breast cancers.
Mid-Year Progress Report:
The over arching goal of this project is to investigate the mechanism by which estrogen (E2) regulates breast cancer growth by identifying novel genes involved in the process and then targeting them therapeutically. Validation of these genes will assist in identifying the patients who will benefit from endocrine therapy and result in reduced mortality for breast cancer patients. GREB1, regulated by estrogen in breast cancer cells, has been identified as a gene significantly affected by E2 stimulation in breast cancer.
Previous studies completed by Dr. Lippman's research team using interfering siRNA to reduce GREB1 levels revealed that inhibition of GREB1 expression prevented breast cancer cell proliferation. Interfering RNA is a means of specifically turning off any given gene and thereby testing its role in a cell or tumor. Thus, GREB1 may be an important gene in the progression of estrogen receptor positive (ER+) breast cancer and may serve as a potential prognostic marker or therapeutic target. Further characterization of the function of GREB1 in normal breast and breast cancer is required. With the support of BCRF, these studies are focused on the detection of the GREB1 protein in primary breast cancers and elucidating its role in ER+ breast tumors. Dr. Lippman’s team has successfully developed a number of research tools and protein expression systems for use in experiments towards answering these critical objectives. Their main goal is determine if GREB1 is a suitable marker for identifying patients and whether blocking its action could provide a new therapy for patients.
Bio:
Marc Lippman is currently Kathleen & Stanley Glaser Professor, Chairman, Department of Medicine, Leonard M. Miller School of Medicine at the University of Miami. He is also Adjunct Professor of Internal Medicine, University of Michigan Medical School in Ann Arbor, MI.
Dr. Lippman was previously the John G. Searle Professor and Chair, Department of Internal Medicine at the University of Michigan Health System. He was also the Director of the Lombardi Cancer Research Center, Professor and Chairman of the Department of Oncology, and Professor of Medicine at Georgetown University Medical School. In addition, he was Chief of the Division of Hematology-Oncology. Prior to his appointment at Georgetown, he was Head of the Medical Breast Cancer Section of the Medicine Branch of the National Cancer Institute.
Dr. Lippman received his B.A., magna cum laude from Cornell (1964) and his M.D. from Yale where he was elected to Alpha Omega Alpha (1968). He completed internship and residency in internal medicine at Johns Hopkins Hospital on the Osler Service and further fellowship training at the National Cancer Institute where he remained until 1988 when he went to Georgetown University. He assumed his current position at the University of Michigan in January 2001.
Dr. Lippman has attempted to bridge the gap between basic tumor biology and clinical application in the field of breast cancer. His work established the critical role of growth factors in human breast cancer and in an extensive series of studies has characterized and purified these factors and designed antitumor therapies based on these insights. He has received the Clinical Investigator Prize of the American Federation for Clinical Research, the Rosenthal Award of the American Association for Cancer Research, the American Cancer Society Lectureship awarded by the American Society for Clinical Oncology, the Astwood Prize of the Endocrine Society, and the Brinker International Prize for Basic Research in Breast Cancer. He has authored over 500 publications and one of the standard texts on breast cancer, and has successfully pursued clinical trials for every stage of breast cancer patients with most of these studies reflecting his special joining of clinical with basic science.
