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BCRF Grantee Since

2006

Area(s) of Focus

Stephen J. Weiss, MD

E. Gifford and Love Barnett Upjohn Professor of Internal Medicine and Oncology
Chief, Molecular Medicine & Genetics
University of Michigan
Ann Arbor, Michigan

Current Research

Recent work has focused on identifying the key molecules responsible for supporting the aggressive behavior of triple negative breast cancers, particularly the ability of the cancer cells to metastasize and recruit “helper cell” populations (e.g. endothelial cells – the cells that comprise blood vessels – and mesenchymal stem cells – a normal cell population whose function can be co-opted by cancer cells to help the neoplasm grow). These efforts have led to the identification of a new signaling pathway (known as the Wnt cascade) that allows triple negative breast cancer cells to grow and invade local tissues. Dr. Weiss has also characterized new mechanisms that allow cancer cells to promote new blood vessel formation (i.e. angiogenesis) and discovered potent activators of mesenchymal stem cell and breast cancer cell growth. In addition, his team has described new mechanisms that define the ability of breast cancer cells to mobilize molecular scissors (termed proteinases) that serve to control disease progression. Their research in 2013-2014 will continue along these lines.

Mid-Year Summary

In delineating the molecular mechanisms that underlie the unregulated growth and metastatic potential of breast cancer cells, increasing evidence has focused on the ability of the abnormal cells to inappropriately express a series of molecules that normally control cellular processes associated with early embryonic development. That is, in the developing embryo, precursor cells (commonly referred to as “stem cells”) rapidly alter their identity or “differentiate” to generate the various cell types found in adult tissues (e.g., brain, liver, heart, breast, etc.) and to move or “invade” through the tissues of the developing organism to populate their designated sites in the overall body plan. Hence, the control of cell differentiation and cell invasion programs are part and parcel of the normal developmental processes that are normally extinguished in adult tissues. The inappropriate “reactivation” of these programs in normal breast tissue via inborn (e.g., BRCA1) or spontaneous (p53) mutations in the human genome drives both the unregulated growth and spread of breast cancer cells to distant sites in the body. Increasing evidence suggests that two potentially important molecules responsible for triggering these events in breast cancer are i) Snail1, a protein that binds to DNA at hundreds of sites, thereby controlling the expression of numerous downstream proteins that oversee cell behavior and ii) MT1-MMP, a type of molecular “scissors” that controls the ability of cells to move or “cut” their way through tissues. However, given the number of abnormally expressed molecules in breast cancer tissues (ranging from the hundreds to thousands of proteins), the importance of Snail1 or MT1-MMP in driving the breast cancer program have remained controversial. Recent work from the Weiss laboratory now demonstrates that Snail1 as well as MT1-MMP are critical “drivers” of the breast cancer program and that therapeutic interventions directed against these molecules could impact patient morbidity as well as mortality.

Bio

After completing his BA, MD, and internship at Ohio State University and Washington University, Dr. Weiss was recruited to the Division of Hematology/Oncology at the University of Michigan in 1978. Most recently, Dr. Weiss served as the Division Chief of Molecular Medicine & Genetics and the Director of the Molecular Mechanisms of Disease Program at the University of Michigan. In 2006, he joined the Life Sciences Institute as a Research Professor.

Dr. Weiss' research efforts have long focused on the mechanisms used by cancer cells to remodel tissue structure during events ranging from inflammatory disease and angiogenesis to cancer. His highly cited works on the role of metalloproteinases in regulating these pathologic events have appeared consistently in top-ranked journals such as Science, Nature, Genes & Development, Journal of Cell Biology, Proceedings of the National Academy of Sciences, and Cell.

Dr. Weiss has received numerous honors and awards in the course of his academic career, including the National Young Investigator Award from the American Society for Clinical Research and a MERIT Award from the National Institutes of Health (NIH). He is a member of the American Society for Clinical Investigation, the Association of American Physicians, and in 2001 was selected as a member of the Institute of Medicine of the National Academy of Sciences. Dr. Weiss has also served on numerous committees at the NIH as well as the National Cancer Institute, and served as the Editor-in-Chief of Journal of Clinical Investigation from 1997 to 2002.