Joan Goverman

University of Washington, USA

Title: Novel mechanisms of tolerance induction in CD8+ MBP-specific T-cells

Biography:

Dr. Goverman received a Bachelors degree in Chemistry from Brandeis University. She received a Ph.D. in Biological Chemistry from the University of California, Los Angeles in 1981. A postdoctoral fellowship at UCLA was followed by additional training at the California Institute of Technology. She is now a Professor and Acting Chair of the Department of Immunology at the University of Washington.

Dr. Goverman's research focuses on the pathogenesis of autoimmune disease. Autoimmunity is believed to arise from a breakdown in tolerance to self-antigens. Multiple sclerosis (MS) is an autoimmune disease in which self-reactive T cells target myelin proteins in the central nervous system (CNS). The research program focuses on defining mechanisms that maintain immune tolerance to myelin proteins, determining triggers that break this tolerance, and elucidating how myelin-specific T cells mediate disease. We are interested in the precise mechanisms by which myelin-specific T and B cells contribute to autoimmunity in the CNS, and the role of regulatory T cells in suppressing this disease. With these objectives in mind, we have engineered a number of animal models using T cell receptor transgenic mice that express either CD4+ or CD8+ T cell receptors specific for myelin basic protein. These models revealed novel mechanisms of tolerance induction, as well as generated experimental systems that recapitulate more faithfully the complex pathology seen in MS patients. Using these tools, we are investigating the contribution of CD4+ and CD8+ T cells and B cells to autoimmunity in the CNS.  We are also defining the parameters that govern T cell trafficking in the CNS, the effector mechanisms that propagate disease and how inflammatory responses are regulated in different microenvironments in the CNS. Our long-term goal is to further our understanding of the pathogenesis of this autoimmune disease in order to define potential targets for therapeutic intervention.