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Department of Immunology 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. A member of the Department of Molecular Biotechnology when it was founded at the University of Washington in 1992, Dr. Goverman joined the Department of Immunology in 1994. Our research focuses on understanding the mechanisms underlying the pathogenesis of autoimmune disease. Our primary area of interest is delineating mechanisms that lead to the development of multiple sclerosis. Multiple sclerosis is believed to be an autoimmune disease in which self-reactive T cells that recognize myelin proteins escape normal mechanisms of immune tolerance and become activated, causing inflammation and destruction of myelin in the central nervous system (CNS). We study the mechanisms that normally maintain immune tolerance to myelin proteins, triggers that break this tolerance, the characteristics of T cells that mediate the disease and the effector mechanisms that ultimately cause tissue damage. We have developed a number of new animal models using T cell receptor transgenic mice that express either CD4+ or CD8+ T cell receptors specific for different myelin proteins. These models recapitulate different aspects of the complex pathology seen in MS patients, and have allowed us to discover novel mechanisms of maintaining tolerance. 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. Graduate students currently training in the Goverman lab: Sarah Lee (Immunology); Sarah Swarts (MSTP); Selected publications from Ph.D. students in the Goverman laboratory: Huseby, E.S., D. Liggitt, T. Brabb, B. Schnabel, C. Ohlen and J. Goverman. 2001. A Pathogenic Role for Myelin-Specific CD8+ T Cells in a Model for Multiple Sclerosis. J. Exp. Med. 194:669-676. Seamons, A., Sutton, J., Bai D., Baird. E., Bonn, N., Kafsack, B.F.C., Shabanowitz, J., Hunt, D.F., Beeson, C. and J. Goverman. 2003. Competition Between Two MHC Binding Registers in a Single Peptide Processed From Myelin Basic Protein Influences Tolerance and Susceptibility to Autoimmunity. J. Exp. Med. 197:1391-7. Perchellet, A., Stromnes, I., Pang J. and J. Goverman. 2004. CD8+ T Cells Maintain Tolerance to Myelin Basic Protein by Epitope Theft. Nature Immunology 5:606-614. McBeth, C., Seamons, A., Pizzaro, J.C., Fleischman, S.J., Baker, D., Kortemme, T., J. Goverman, Strong, R.K. 2008. A new twist in TCR diversity revealed by a forbidden ab TCR, J. Mol. Biol. 375:1306-1319. Stromnes I, Cerretti, L, Liggitt D, Harris RA and J Goverman. 2008. Differential Regulation of Central Nervous System Autoimmunity by TH1 and TH17 Cells. Nature Med., 14(3):337-342. Perchellet, A., Brabb, T. and J. Goverman. 2008. Novel Mechanisms of Central Tolerance Eliminate CD8+ T Cells Specific for Myelin Basis Protein. Proc. Natl. Acad. Sci.,105(37):14040-5. Goverman, J. 2009. Autoimmune T Cell responses in the Central nervous System. Nature Rev Imm. 9:393-407. Ji, Q., Perchellet, A. and J. Goverman. 2010. Viral infection triggers central nervous system autoimmunity via activation of CD8+ T cells expressing dual TCRs. Nat Immunol. Jul;11(7):628-34.
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Updated 12/14/2010
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