Knudson, Michael, M.D./Ph.D.

Research in the lab is focused on understanding the molecular basis by which the Bcl-2 family of proteins regulates cell death, cell proliferation and ultimately controls cancer development. The Bcl-2 oncogene has been identified as a cause of B-Cell Lymphoma and a potent inhibitor of apoptosis. Over 15 mammalian genes have been identified with homology to Bcl-2. These Bcl-2 family members can be segregated based on the ability of these genes to inhibit (Bcl-2 like) or promote (Bax like) cell death. The lab employs transgenic and knockout murine models as well as cell culture models to study the regulation of cell death, cell proliferation, and oncogenesis by the Bcl-2 family. Many studies in the lab stem from our unexpected finding that Bax accelerates the development of lymphoma in p53 deficient mice (Cancer Research, 2001) and is associated with increased chromosome instability (CIN) (Cell Death and Differntiation, 2003 Cancer Research, 2007). Understanding the molecular basis for this observation is a major emphasis of the laboratory. Thus one major interest centers on the role of Reactive Oxygen Species (ROS) in the oncogenesis and CIN. Other studies are focused on examining the mechanism of Bax induced chromosomal stability and cancer formation. Finally, recent studies have shown that defects in autophagy have recently been linked to Cancer and chromosome instability and that regulators of autophagy are known to interact with Bcl-2 family members. Current studies are exploring the cross talk between authophagy and apopototic pathways in cancer.