Marc E. Lippman, MD

2012-2013 BCRF Project:
(made possible by generous support from Michael Reese Enterprises

An extraordinary amount of research over the last several years has begun to unravel the changes that occur in normal breast cells that allow them to grow abnormally, invade the bloodstream, and, ultimately, implant (metastasize) in other organs.

In 2012-2013, Dr. Lippman's team will pursue a novel aspect of cancer: the ability of breast cancer cells to induce remote tissues to serve as sites of metastases. They believe that a critical component of metastatic disease involves a failure of immune surveillance. They have developed a robust model in which human breast cancers metastasize from the mammary fat pad. Using this model, they have found that many breast cancers can secrete factors called cytokines that circulate widely and recruit a very specific class of immune suppressor cells (myeloid derived suppressor cells, MDSCs) to tissues throughout the body. They have also shown that the recruitment of these MDSCs is required for metastasis. In addition to breast cancer, several other common systemic conditions, including depression and obesity, are associated with high levels of some of the same cytokines. Dr. Lippman's team will explore the role of these cytokines in altering immune defenses, and how those alterations promote human metastatic breast cancer. This work has the potential to uncover a critical link between breast cancer metastasis and diseases associated with altered cellular immune functions (including depression and obesity), which may lead to novel therapeutic interventions.

Mid-year Progress: The ability of breast cancer cells to modulate the systemic environment is an important event in the overall process of metastasis. This, and how it may ultimately favor the progression of metastatic disease, is the focus of Dr. Lippman's research.

Dr. Lippman's lab has a robust group of laboratory models of breast cancer that include breast cancer cells belonging to several breast cancer subtypes seen in patients. In these models, human breast cancer cells are able to grow as a tumor in the mammary fat pads, and some of them are able to form metastases in distant sites such as lymph nodes, liver, bone and lung, sites often found in breast cancer patients. Using these models, Dr. Lippman's team has focused on elucidating the relationship between factors produced by the tumors, the immune cells that are recruited in each model and the role of these on metastatic behavior. They have now quantified circulating tumor-derived factors and have found that while many breast cancers produce a common group of factors, there are other several different factors found in only some of the tumors. As a consequence, each tumor model has a unique global profile of tumor-secreted factors that may impinge on the immune cells that are recruited by each breast tumor and the systemic environment. With the use of these models, these researchers have also focused on the role of the myeloid cells, including myeloid derived suppressor cells (MDSCs) and macrophages, in the metastatic setting by first establishing the types of MDSCs recruited by each model.

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 position at the University of Michigan in January 2001 and was recruited to the University of Miami in 2008.

Dr. Lippman has focused on bridging 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.