Signaling Through Integrin Adhesion Receptors in Development, Vascular Biology and Cancer.
Integrins represent a ubiquitous family of transmembrane adhesion receptors that transfer biological information between the extracellular and intracellular environments. The general term “integrin signaling” is often used to refer to this process, which is involved in regulating biological events as diverse as embryonic development, synaptic plasticity of the nervous system, innate and adaptive immunity, and the functions of circulating blood cells. Integrin signaling encompasses both “inside-out” signals that regulate integrin affinity and avidity for extracellular ligands and “outside-in” signals that regulate anchorage-dependent cellular responses, such as cell motility and changes in gene expression. Defects in integrin signaling promote certain vascular, inflammatory and neoplastic disorders. The focus of this laboratory is to unravel the molecular basis of integrin signaling as it pertains to development, vascular biology and cancer. In this context, integrin signaling is required for the proliferation and differentiation of stem cells and hematopoietic progenitors into megakaryocytes, for platelet function in hemostasis and thrombosis, for endothelial cell participation in wound healing and angiogenesis, and for tumor progression. Recent work from this laboratory using complementary experimental systems, including human platelets, genetically-modified mice, zebrafish and animal models of neoplasia, indicates that integrin signaling is initiated by their interaction with specific protein kinases, phosphatases and molecular adapters. A current challenge is to integrate the wealth of information obtained from basic research into a complete understanding of integrin signaling, with diagnostic and therapeutic implications for cardiovascular and neoplastic diseases.
Education and Training
BA - Psychology, University of Illinois - 1961-1964
MD - University of Illinois College of Medicine - 1964-1968
Intern/Resident - Boston City Hospital (Harvard) - 1968-1970
Fellow - Hematology, Boston City Hospital, Thorndike Lab, Harvard - 1970-1971