Division of Cardiovascular Medicine

Timothy O'Toole PhD
University of Louisville
Department of Cardiology
580 S. Preston St. Rm. 421
Louisville, KY 40202
502 852-5886
tim.otoole@louisville.edu

Dr. O'Toole's research interests are focused in two areas. Upon activation, platelets acquire an adhesive phenotype and play central roles in thrombosis and the development of atherosclerosis. Dr. O'Toole has had a long interest in the signaling mechanisms leading to platelet activation and in the role that integrin adhesion receptors play in platelet biology. Current studies will attempt to determine the mechanisms whereby environmental toxins or stimuli enhance platelet adhesiveness resulting in pro-thrombotic and pro-atherogenic phenotypes. Secondly, in response to inflammatory signals or oxidative stress, platelets and other vascular or hematopoietic cell types generate reactive oxygen species (ROS). Additional studies will seek to understand the mechanisms and consequences of ROS production by these cells with particular emphasis regarding the potential role these agents might play in atherosclerotic development and ultimate plaque rupture.

Selected publications:

Buensuceso, C.B., Woodside,D., Huff, J.L., Plopper, G.E., and O’Toole, T.E.: The WD protein Rack1 mediates PKC and integrin dependent cell migration. J. Cell Sci. 114: 1691-1698, 2001.

Felding-Habermann, B., Fransvea, E., O’Toole, T.E., Manzuk, L., Faha, B., and Hensler, M.: Involvement of tumor cell integrin avb3in hematogenous metastasis of human melanoma cells. Clin. Exp. Metastasis 19: 427-436, 2002.

Cox, E. A., Bennin, D., Doan, A.T., O'Toole, T., and Huttenlocher, A.: Rack1 regulates integrin-mediated adhesion, protrusion and chemotactic cell migration via its Src binding site. Mol Biol. Cell. 14: 658-669, 2003.

De, S., Razorenova, O., McCabe, N.P., O’Toole, T., Qin, J., and Byzova, T.V.: VEGF-integrin interplay controls tumor growth and vascularization. PNAS 102: 7589-7594, 2005.

O’Toole, T.E., Bialkowska, K., Li, X. and Fox J.E.B.: Recruitment of Tiam by 14-3-3z: a novel mechanism for integrin-dependent Rac activation in a spatiotemporal manner. J. Cell Biol. Submitted.