Cellular and molecular studies of viral and autoimmune encephalitides
My laboratory studies the pathogenesis of neuroinflammatory diseases of the central nervous system (CNS). 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 resident neural cells. 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. Our studies over the past few years have led us to focus on the roles of cytokines and chemokines in the regulation of blood-brain barrier permeability to protective versus pathogenic leukocytes, and to West Nile virus (WNV), a positive strand flavivirus that may enter the CNS and cause encephalitis. These inflammatory cues also regulate CNS repair by neural progenitor cells (NPCs) in mice with viral infection or demyelinating diseases. Aspects related to NPC-mediated repair include defining the localizing, proliferative and differentiation cues that lead to successful repair of damaged neurons and myelin.