Structure and biology of integrin adhesive receptors for extracellular matrix proteins
Since 2003, Dr. Santoro has led the Department of Pathology, Microbiology and Immunology to national prominence in research, clinical practice and education. Dr. Santoro plays a leading role in the development of personalized and genomic medicine at Vanderbilt and at the national level. He is a member of the Personalized Health Care Committee of the College of American Pathologists and chairs the working group that compiles and edits the Genome Analysis Resource Guide and the Molecular Pathology Resource Guide. Dr. Santoro has also been a pioneer in the elucidation of the molecular mechanisms of cellular adhesion to the extracellular matrix and in defining the role of adhesion molecules in disease. His research group is largely responsible for the discovery and characterization of collagen receptors.
He received his M.D. and Ph.D. in Biochemistry from Vanderbilt in 1979. Dr. Santoro went on to complete residency training in laboratory medicine (clinical pathology) at Washington University and Barnes Hospital in St. Louis.
Dr. Santoro is the author of more than 140 publications and has been an Established Investigator of the American Heart Association, a member of the Pathology A Study Section of the National Institutes of Health, and a member of the editorial board of BLOOD. He has been elected to membership in the American Society of Clinical Investigation (ASCI) and the Association of American Physicians (AAP). Throughout his career, Dr. Santoro has played an active role in the clinical laboratory aspects of hemostasis and thrombosis. He is the author of numerous articles and textbook chapters in the field.
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.