University of Michigan
Ann Arbor, Michigan
E. Gifford and Love Barnett Upjohn Professor of Internal Medicine & Oncology Division of Genetic Medicine Department of Internal Medicine Rogel Cancer Center Professor, Cell and Molecular Biology Program Research Professor Life Sciences Institute
Validating new therapeutic targets to prevent metastatic breast cancer.
Aggressive breast cancers arise as a result of tumor cells’ ability to invade local tissues, gain access to blood or lymphatic vessels, and exit at distant sites where the cells grow anew—a process called metastasis. Dr. Weiss is studying a sub-population of breast cancer cells, termed cancer stem cells, that play a critical role in metastasis. The evolution of breast cancer stem cells has remained unclear, and this has thwarted the development of new therapeutic interventions. Identifying important players in cancer stem cell growth and survival could provide important insights for the development of new therapeutic interventions for breast cancer patients.
Dr. Weiss and his team have discovered a role for a breast cancer-associated gene called MT1-MMP in driving breast cancer’s ability to build new blood vessels and metastasize. However, they also found that this gene is expressed in blood vessels surrounding growing tumors. Moreover, inhibiting its activity controls both the ability of metastatic cells to proliferate as well as the ability of breast cancer cells to thwart immune system responsiveness.
Over the next year, Dr. Weiss and his team will continue to characterize new processes that promote breast cancer stem cell formation and their continued growth. They will further define the roles played by MT1-MPP and a related gene, MMP14, in controlling cancer cell-blood vessel interactions critical to metastatic growth, and in impacting immune cell functions central to anti-tumor cell activity. The team ultimately aims to use this information to target drivers of MT1-MMP/MMP14 and aid in the design of new therapeutics capable of targeting cancer stem cells.
After completing his postdoctoral training at Washington University, Dr. Weiss was recruited to the University of Michigan in 1982 where he assumed the rank of Professor in 1988. In 1991, he was named as the first recipient of the Upjohn Professorship in Oncology, a position that he continues to hold. Dr. Weiss has also served as the Director of the Molecular Mechanisms of Disease Program and the Chief of the Division of Molecular Medicine & Genetics in the Department of Internal Medicine at the University of Michigan as well as the Associate Director of Basic Science Research in the University of Michigan Comprehensive Cancer Center. In 2006, he joined the Life Sciences Institute as a Research Professor. He is a member of the American Society of Clinical Investigation, the Association of American Physicians, National Academy of Medicine, and served as the Editor-in-Chief of the Journal of Clinical Investigation.
Dr. Weiss’ research efforts have long focused on the mechanisms used by breast cancer cells to remodel tissue structures during tumor progression, invasion and metastasis. His studies on the roles of transcription factors and proteolytic enzymes (particularly Snail family members and the membrane-anchored matrix metalloproteinases, respectively) in regulating these pathologic events in vitro and in vivo have appeared in top-ranked journals such as Science, Nature and Cell.
2006
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