Samuel A. Santoro, M.D., Ph.D.
Dorothy B. and Theodore R. Austin Professor and Chair
Assistant to the Chair: Debra Ferrin, debra.ferrin@Vanderbilt.Edu
Campus Mail address:
Pathology, Microbiology and Immunology-3rd Fl
C-3321 MCN (2561)
US Mailing address:
Vanderbilt University School of Medicine
Dept Pathology, Microbiology and Immunology-3rd Fl
Nashville, TN 37232-2561
Structure and biology of integrin adhesive receptors for extracellular
The molecular mechanisms of cell-substrate adhesion and the biologic roles of cellular adhesion are the foci of our research program. Most of our studies are centered on the alpha 2/beta 1 integrin, a cell surface receptor for collagen that was originally identified and characterized in our laboratory. Current efforts are devoted to elucidation of the structural basis of ligand recognition by the integrin, the structural basis of integrin activation and the roles of the alpha 2/beta 1 and related integrins in complex biological processes such as differentiation, development, wound healing and repair, tumor cell invasion and metastasis, and hemostasis and thrombosis.
Ongoing projects include: 1) elucidation of the structural basis by which the integrin recognizes and binds both collagenous and noncollagenous ligands, 2) elucidation of the structural basis of integrin activation that permits higher affinity binding of some ligands or that is required for the binding of other ligands, 3) exploration of the role of altered integrin expression in the invasive and metastatic behavior of tumor cells, 4) definition of the structural and biologic basis of MMP-1 (matrix metalloproteinase-1) interactions with the integrin and the role of the interaction in regulating cell surface matrix metalloproteinase activity in wound repair and related events, 5) examination of the role of integrin-mediated cell-matrix interactions in the establishment and maintenance of the differentiated epithelial phenotype, and 6) and elucidation of the structural basis and pathbiologic function of the alpha 2/beta 1 integrin as a receptor for echoviruses and reoviruses. In addition, we continue to identify new ligands that implicate the alpha 2/beta 1 integrin in novel facets of biology and pathology.
Our studies combine the application of modern protein and peptide biochemistry, immunochemical and molecular genetic approaches (including knockout mice) to address the fundamental roles and mechanisms of cellular adhesion in complex cell biological processes.