The Laboratory of Tanya Mayadas, Ph.D.
HMS
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Tanya Mayadas, Ph.D.Welcome

An inflammatory response requires the recruitment of innate immune cells (e.g. neutrophils and monocyte/macrophages) through their interaction with the endothelium, and the induction of processes that allow them to engulf targets, release proteinases and generate reactive oxygen species to eliminate the offending stimuli. We are particularly interested in understanding neutrophil responses to targets opsonized with antibody (forming immune complexes) or complement as these responses are critical for host defense but also contribute to tissue injury associated with autoimmune and inflammatory diseases. In particular, we aim to understand how leukocyte adhesion receptors on innate immune cells coordinate neutrophil responses and relay signals to achieve desired effector functions. Using knock-out mice, biochemical approaches and in vivo models of inflammation we have i) defined a novel function for the b2 integrin Mac-1 in triggering neutrophil apoptosis following phagocytosis which has implications for the resolution of inflammation ii), defined a new role for Fcg receptors (which recognize IgG) in recruitment of neutrophils to immune complexes deposited within the vasculature and iii) assigned specific roles for the two TNF receptors (TNFR1 and TNFR2) in the pathogenesis of chronic immune complex induced glomerulonephritis. We are currently carrying out studies to further delineate the contribution of Fcg receptors and b2 integrins, and their signaling pathways, in neutrophil recruitment and cytotoxicity and define the mechanisms of TNFR2 mediated glomerular injury.

Another developing area of interest is to examine how remodeling of endothelial cell junctions, which is required for vascular permeability and leukocyte transmigration, is regulated. We focus on understanding the importance of the Rap and Rho GTPases and regulators of these GTPases in this process. Our recent work has shown that activation of Rap GTPases through its cAMP responsive guanine exchange factor markedly enhanced basal endothelial barrier function, and counteracted thrombin induced hyperpermeability, through effects on the cortical actin and down-regulation of Rho GTPase activation. We are at the present further evaluating mechanisms of Rap GTPase function in the regulation of endothelial cell barrier function.

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This page last updated: January 10, 2008
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