My laboratory focuses on the molecular mechanisms responsible for inflammation-associated dysfunction and damage in CNS with the goal of identifying potential therapeutic targets for the treatment of neuroinflammatory diseases. We have focused on two components of CNS inflammatory states: the mechanism of leukocyte recruitment into the CNS and the direct effects of inflammatory mediators on neurons. Common to both of these is the action of chemokines, which both recruit leukocytes into the CNS and signal through chemokine receptors present on neural cells, affecting their function and survival. Our experimental approach involves the development of in vitro and in vivo models of CNS mononuclear cell recruitment and neural cell chemokine receptor signaling responses. Studies using in vitro models of neural cell types focus on the role of chemokines and their receptors in neuronal and glial cell activation and survival. Using mice with targeted deletions of chemokine receptors we are evaluating how inflammation triggers both neuroprotective and neuroinjurious mechanisms. Studies using in vivo models for both autoimmune and viral encephalitides focus on identifying the chemokines and chemokine receptors responsible for the recruitment of mononuclear cells into the CNS during normal and inflammatory states and the mechanisms of chemokine up-regulation. Using mice with transgenic T cell receptors directed at CNS and non-CNS antigens, mice with targeted deletion for various chemokines and their receptors, as well as small molecule inhibitors of chemokine receptors we are mapping the chemokine expression patterns responsible for the initial migration of activated T cells into the CNS, determining the fate of T cells that do or do not encounter their antigens and examining the inflammatory responses that occur upon antigen recognition. Our viral models utilize mice infected with cytopathic (West Nile virus) and noncytopathic (lymphocytic choriomeningitis virus) RNA viruses that target neurons within the CNS.

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Infectious diseases

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