Lab Research Focus
My research interests have been on the production and regulation of several components in the complement system. These interests focused on the central nervous system (CNS) based on growing evidence for a role for complement in CNS diseases. This led us to examine for the production and cytokine-mediated regulation of additional activation components, as well as, complement regulatory proteins. It is now clear that, at least in vitro, most if not all complement proteins can be synthesized by astrocytes, microglia, and to our surprise, neurons. Since these initial observations, we have moved into in vivo models systems. Using a variety of disease models, including bacterial meningitis, brain trauma, experimental allergic encephalomyelitis (EAE) and a murine stroke model, we have demonstrated that a number of complement proteins and receptors are widely produced in the intact CNS under pathological conditions. We have recently expanded our interest in complement in the CNS to include C-reactive protein (CRP) and beta2-integrins and several of their ligands. We are examining the role of these molecules in EAE using several complement and adhesion molecule knock-out mice. In addition, we are using mice transgenic for CRP and several transgenic mouse lines that express either the complement regulatory protein (sCrry) or the complement anaphylatoxins, C3a or C5a, only in the CNS under the control of an astrocyte-specific promoter. Our data suggest that targeting these molecules has therapeutic value.
In other studies, we are examining the role of gamma/delta T cells in autoimmune disease in the CNS with a particular interest in trafficking and activation mechanisms. We have recently shown that these cells are critical to the development of EAE, but surprisingly little is known about the function of these cells in the pathogenesis of demyelinating disease.
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