Research in the Klein laboratory focuses on the pathogenesis of neuroinflammatory diseases of the central nervous system (CNS).
Dr. Klein is interested in the cellular and molecular mechanisms that orchestrate inflammation during both viral and autoimmune encephalitides via endothelial-immune cell interactions. Her 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 stem cells (NSCs) in mice with viral infection or demyelinating diseases. Aspects related to NSC-mediated repair include defining the localizing, proliferative and differentiation cues that lead to successful repair of damaged neurons and myelin.
Dr. Klein's experimental approach involves the development of in vitro models of the blood-brain barrier to study the CNS entry of WNV, mononuclear cells, and of the signaling responses that regulate vascular permeability. Studies using in vivo models for both autoimmune and WNV encephalitides focus on identifying the localizing cues that control leukocyte entry and persistent inflammation. These studies will advance our understanding of normal CNS immune surveillance and its relationship to the wide range in inflammatory patterns observed in various neuroinflammatory diseases. This information will also lead to the identification of novel therapeutic targets, which is much needed in an era where there is little to offer patients with these diseases.