Martin A. Schwartz

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Primary Appointment

Professor of Research

Education

  • BA, Chemistry, New College, Sarasota, FL
  • PhD, Physical Chemistry, Stanford University

Research Interests

Integrin Signaling and Its Relevance to Mechanotransduction, Cancer and Vascular Disease

Research Description

Regulation of cell behavior by adhesion to extracellular matrix (ECM) is a fundamental fact of multicellular life. 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 1980âs, 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 current research involves elucidating basic mechanisms of integrin signaling, including the connections between integrins and Rho family GTPases and c-Abl tyrosine kinase. This work includes developing and using new fluorescence-based assays to visualize activation of signaling molecules in living cells. We are also studying how integrins and Rho family GTPases participate in mechanotransduction. The lab also has two applied projects relevant to developing new cancer therapies. We are studying endothelial cell migration with the goal of developing anti-angiogenic therapies. We are also studying how integrins modulate the response of cells to DNA damage with the goal of improving chemo and radiation therapy.

Personal Statement

Regulation of cell behavior by adhesion to extracellular matrix (ECM) is a fundamental fact of multicellular life. 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 1980âs, 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 current research involves elucidating basic mechanisms of integrin signaling, including the connections between integrins and Rho family GTPases and c-Abl tyrosine kinase. This work includes developing and using new fluorescence-based assays to visualize activation of signaling molecules in living cells. We are also studying how integrins and Rho family GTPases participate in mechanotransduction. The lab also has two applied projects relevant to developing new cancer therapies. We are studying endothelial cell migration with the goal of developing anti-angiogenic therapies. We are also studying how integrins modulate the response of cells to DNA damage with the goal of improving chemo and radiation therapy.

Selected Publications

Thomas S, Overdevest JB, Nitz MD, Williams PD, Owens CR, Sanchez-Carbayo M, Frierson HF, Schwartz MA, Theodorescu D, Src and caveolin-1 reciprocally regulate metastasis via a common downstream signaling pathway in bladder cancer., 2011; Cancer Res. 71(3) 832-41.

Parsons JT, Horwitz AR, Schwartz MA, Cell adhesion: integrating cytoskeletal dynamics and cellular tension., 2010; Nat Rev Mol Cell Biol. 11(9) 633-43.

Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, McLean MA, Sligar SG, Chen CS, Ha T, Schwartz MA, Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics., 2010; Nature. 466(7303) 263-6.

Feaver RE, Gelfand BD, Wang C, Schwartz MA, Blackman BR, Atheroprone hemodynamics regulate fibronectin deposition to create positive feedback that sustains endothelial inflammation., 2010; Circ Res. 106(11) 1703-11.

Schwartz MA, Remembrance of dead cells past: discovering that the extracellular matrix is a cell survival factor., 2010; Mol Biol Cell. 21(4) 499-500.

Balasubramanian N, Meier JA, Scott DW, Norambuena A, White MA, Schwartz MA, RalA-exocyst complex regulates integrin-dependent membrane raft exocytosis and growth signaling., 2010; Curr Biol. 20(1) 75-9.

Petzold T, Orr AW, Hahn C, Jhaveri KA, Parsons JT, Schwartz MA, Focal adhesion kinase modulates activation of NF-kappaB by flow in endothelial cells., 2009; Am J Physiol Cell Physiol. 297(4) C814-22.

Hahn C, Orr AW, Sanders JM, Jhaveri KA, Schwartz MA, The subendothelial extracellular matrix modulates JNK activation by flow., 2009; Circ Res. 104(8) 995-1003.

Wu Y, Moissoglu K, Wang H, Wang X, Frierson HF, Schwartz MA, Theodorescu D, Src phosphorylation of RhoGDI2 regulates its metastasis suppressor function., 2009; Proc Natl Acad Sci U S A. 106(14) 5807-12.

Moissoglu K, McRoberts KS, Meier JA, Theodorescu D, Schwartz MA, Rho GDP dissociation inhibitor 2 suppresses metastasis via unconventional regulation of RhoGTPases., 2009; Cancer Res. 69(7) 2838-44.

Dzamba BJ, Jakab KR, Marsden M, Schwartz MA, DeSimone DW, Cadherin adhesion, tissue tension, and noncanonical Wnt signaling regulate fibronectin matrix organization., 2009; Dev Cell. 16(3) 421-32.

Schwartz MA, Cell biology. The force is with us., 2009; Science. 323(5914) 588-9.

Sebbagh M, Santoni MJ, Hall B, Borg JP, Schwartz MA, Regulation of LKB1/STRAD localization and function by E-cadherin., 2009; Curr Biol. 19(1) 37-42.

Hahn C, Schwartz MA, Mechanotransduction in vascular physiology and atherogenesis., 2009; Nat Rev Mol Cell Biol. 10(1) 53-62.

Hahn C, Schwartz MA, The role of cellular adaptation to mechanical forces in atherosclerosis., 2008; Arterioscler Thromb Vasc Biol. 28(12) 2101-7.

Harry BL, Sanders JM, Feaver RE, Lansey M, Deem TL, Zarbock A, Bruce AC, Pryor AW, Gelfand BD, Blackman BR, Schwartz MA, Ley K, Endothelial cell PECAM-1 promotes atherosclerotic lesions in areas of disturbed flow in ApoE-deficient mice., 2008; Arterioscler Thromb Vasc Biol. 28(11) 2003-8.

Schwartz MA, McRoberts K, Coyner M, Andarawewa KL, Frierson Jr, Sanders JM, Swenson S, Markland F, Conaway MR, Theodorescu D, Integrin agonists as adjuvants in chemotherapy for melanoma., 2008; Clin Cancer Res. 14(19) 6193-7.

Schwartz MA, DeSimone DW, Cell adhesion receptors in mechanotransduction., 2008; Curr Opin Cell Biol. 20(5) 551-6.

Orr AW, Hahn C, Blackman BR, Schwartz MA, p21-activated kinase signaling regulates oxidant-dependent NF-kappa B activation by flow., 2008; Circ Res. 103(6) 671-9.

Meller J, Vidali L, Schwartz MA, Endogenous RhoG is dispensable for integrin-mediated cell spreading but contributes to Rac-independent migration., 2008; J Cell Sci. 121(12) 1981-9.

Schwartz MA, The importance of stupidity in scientific research., 2008; J Cell Sci. 121(11) 1771.0.

Hall B, McLean MA, Davis K, Casanova JE, Sligar SG, Schwartz MA, A fluorescence resonance energy transfer activation sensor for Arf6., 2008; Anal Biochem. 374(2) 243-9.

Meller N, Westbrook MJ, Shannon JD, Guda C, Schwartz MA, Function of the N-terminus of zizimin1: autoinhibition and membrane targeting., 2008; Biochem J. 409(2) 525-33.

Balasubramanian N, Scott DW, Castle JD, Casanova JE, Schwartz MA, Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts., 2007; Nat Cell Biol. 9(12) 1381-91.

Stockton R, Reutershan J, Scott D, Sanders J, Ley K, Schwartz MA, Induction of vascular permeability: beta PIX and GIT1 scaffold the activation of extracellular signal-regulated kinase by PAK., 2007; Mol Biol Cell. 18(6) 2346-55.

Reutershan J, Stockton R, Zarbock A, Sullivan GW, Chang D, Scott D, Schwartz MA, Ley K, Blocking p21-activated kinase reduces lipopolysaccharide-induced acute lung injury by preventing polymorphonuclear leukocyte infiltration., 2007; Am J Respir Crit Care Med. 175(10) 1027-35.

Orr AW, Stockton R, Simmers MB, Sanders JM, Sarembock IJ, Blackman BR, Schwartz MA, Matrix-specific p21-activated kinase activation regulates vascular permeability in atherogenesis., 2007; J Cell Biol. 176(5) 719-27.

Moissoglu K, Slepchenko BM, Meller N, Horwitz AF, Schwartz MA, In vivo dynamics of Rac-membrane interactions., 2006; Mol Biol Cell. 17(6) 2770-9.

Orr AW, Ginsberg MH, Shattil SJ, Deckmyn H, Schwartz MA, Matrix-specific suppression of integrin activation in shear stress signaling., 2006; Mol Biol Cell. 17(11) 4686-97.

Moissoglu K, Schwartz MA, Integrin signalling in directed cell migration., 2006; Biol Cell. 98(9) 547-55.

Schwartz MA, Horwitz AR, Integrating adhesion, protrusion, and contraction during cell migration., 2006; Cell. 125(7) 1223-5.

Orr AW, Helmke BP, Blackman BR, Schwartz MA, Mechanisms of mechanotransduction., 2006; Dev Cell. 10(1) 1-20.