The Laboratory of Brian Fife at the University of Minnesota

Brian T Fife

Dr. Brian Fife is an Associate Professor of Medicine within the Division of Rheumatic and Autoimmune Diseases at the University of Minnesota Medical School. He joined the division in February, 2008. He is also a member of the interdisciplinary Center for Immunology and its Autoimmunity Program. Dr. Fife is a faculty member for the Microbiology, Immunology, and Cancer Biology (MICaB) as a Graduate Student Ph.D. Program adviser and mentor. In December 2001, Dr. Fife graduated from Northwestern University Medical School. It is there that he initiated his research interests in autoimmune mediated diseases. Following graduation, Dr. Fife joined the Diabetes Center in the Department of Medicine at the University of California at San Francisco for postdoctoral research. The major focus of his research program is the restoration of immunological self tolerance for treatment of autoimmunity.

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Research in my lab is focused on understanding the fundamental mechanisms that regulate T lymphocytes during autoimmune disease such as Type 1 diabetes mellitus (T1DM). T1DM is an autoimmune disorder resulting from the T cell mediated destruction of the insulin producing cells within the pancreas. At the root of autoimmunity lies the most important aspect of immune regulation, the ability to discriminate between self and non-self. This highly selective response is characterized by a complicated set of mechanisms which regulate T lymphocyte activity. Autoimmunity results when these mechanisms fail. Recently, we have generated a powerful treatment protocol to selectively target autoreactive cells. Using this type of approach allows us to re-educate the immune system to selectively silence destructive immune responses. Thus in effect, restore a state of self-tolerance and prevent further tissue destruction. We have identified two key regulatory pathways that control diabetes and promote tolerance, Cytotoxic T lymphocyte antigen-4 (CTLA-4) and Programmed Death-1 (PD-1). We have shown that these pathways control both anergy induction and long term maintenance of tolerance. Recent studies have focused on the in vivo imaging of the immune response using two photon microscopy. Using this tolerance protocol will allow us to determine the precise roles of these negative regulatory pathways at different stages during disease pathogenesis to control immunity and enhance tolerance.




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