Office phone: (859)323-5913
Fax: (859)257-8994
Lab phone: (859)257-5121
Department of Microbiology, Immunology and Molecular Genetics
Thomas Roszman, Ph.D. |
Professor |
Doctoral studies: Michigan State University. Postdoctoral: Case Western Reserve University. |
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Office phone: (859)323-5913 |
Selected publications |
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| Research statement: The overall objective of our research is to study the role of calpain in regulating integrin-mediated interaction of T-cells with the extracellular matrix (ECM). When T-cells are appropriately signaled, they acquire the ability to adhere to the ECM. Adherence to the ECM proteins is required for T-cells to migrate into inflammatory sites. The binding and migration of T-cells are regulated by plasma membrane proteins, termed integrins, composed of various combinations of either a or b chains. Of particular interest to our research is that T-cells express a4b1 and a5b1 integrins that bind the ECM protein fibronectin (FN) and these receptors are responsible for T-cells entering sites of inflammation. The interaction of these integrins on T-cells with FN results in the translocation and activation of the calcium-activated cysteine protease calpain. Calpain is present in all mammalian cells and causes limited proteolysis of a number of proteins including those associated with the cytoskeleton. Our results show that when T-cells bind to ECM proteins such as FN, calpain translocates from the cytosol to the cytoskeletal/membrane fraction of the cell where it becomes activated. Once activated calpain can cleave a number of proteins which become associated with the focal contact site which develops in the T-cell subsequent to their integrins interacting with their ligands, e.g. FN. We are investigating the biochemical and molecular events which involve calpain when T-cells adhere to, undergo shape change, and migrate after encountering FN. | |
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