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Martin A. Schwartz

Professor of Microbiology and Biomedical Engineering

Ph.D. Stanford University

Phone (434) 243-4813
Fax (434) 924-2828

maschwartz@virginia.edu

Research Interests

Integrin signaling and its relevance to mechanotransduction, cancer and vascular disease

Virtually every cell in vertebrates spends at least a portion of its life cycle adhered to ECM, and this interaction critically regulates cell survival, growth, gene expression and function. Integrins are the major membrane receptors that mediate adhesion of cells to ECM. In doing so they connect the actin cytoskeleton inside the cell to the ECM to provide mechanical integrity. My lab is among those that, in the late 1980.s, showed that integrins also transduce signals. These signals are complex and varied, and appear to mediate many if not most of the regulatory effects of ECM. My laboratory's overall goal is to understand how integrins signal, how these signals regulate cell functions, and how they fit into the larger picture of cell regulation by soluble factors, oncogenes, and mechanical forces.

A major area of our current research involves the role of integrins in mechanotransduction, especially responses of endothelial cells to fluid flow. Atherosclerosis occurs selectively in regions of disturbed flow. Integrins play a key role in transducing forces from flowing blood into biochemical signals that regulate cell behavior. Activation of several inflammatory pathways by flow are mediated by integrins and dependent on the subendothelial extracellular matrix. Local changes in the matrix are observed in atherosclerosis-prone regions of arteries in vivo and appear to play key roles in atherogenesis through their effects on integrin signaling. We are currently working to understand these pathways and use that information to develop new therapeutic approaches.

We are also developing new methods to measure mechanical forces in cells and apply them to cells under fluid flow, developing embryos and cell migration.

Selected Publications

del Pozo, M., Alderson, N., Kiosses, W.B., Chiang, H.H., Anderson, R.G.W., and Schwartz, M.A. Integrins regulate Rac plasma membrane targeting through internalization of membrane domains. Science 303: 839-842

Tzima, El, Irani-Tehrani, M., Kiosses, W.B., Dejana, E., Schultz, D.A., Bngelhardt, B., Cao, G., DeLisser, H., Schwartz, M.A. (2005) Identification of a mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature; 437:426-31.

Orr AW, Sanders JM, Bevard M, Coleman E, Sarembock IJ, Schwartz MA. The subendothelial extracellular matrix modulates NF-kappaB activation by flow: a potential role in atherosclerosis.J Cell Biol. 2005 169:191-202.

Orr, A.W., Helmke, B., Blackman, B.R., Schwartz, M.A. (2006) Mechanisms of mechanotransduction. Dev. Cell 10:11-20.

Orr A.W., Stockton R., Simmers M.B., Sanders J.M., Sarembock I.J., Blackman B.R., Schwartz M.A.(2007) Matrix-specific PAK activation regulates vascular permeability in atherogenesis. J. Cell Biol. 176:719-27.

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