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Diseases/Research Topics Integrin Adhesion Receptors in Blood Cell Development and Function; Adhesion-dependent Signaling in Hematopoietic Cell Biology; Integrin Interactions with Protein Tyrosine Kinases and Phosphatases.

Integrins transfer information between the extracellular and intracellular environments at plasma membrane sites referred to as initial adhesions, focal complexes and focal adhesions. The general term “integrin signaling” is often used to refer to this process, which is involved in regulating processes as diverse as embryonic development and normal blood cell function. Integrin signaling encompasses “inside-out” signals that regulate integrin affinity and avidity for extracellular ligands and “outside-in” signals, whereby ligated integrins regulate anchorage-dependent cellular responses, such as motility and changes in gene expression. Defects in integrin signaling likely 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 hematopoietic and vascular cells, particularly platelets, their precursors cells- megakaryocytes, and endothelial cells. In this context, integrins are required for proliferation and differentiation of stem cells and hematopoietic progenitors into megakaryocytes, for platelet function in hemostasis and thrombosis, and for endothelial cell participation in wound healing and angiogenesis. Recent work from this laboratory indicates that outside-in signaling in these cell types is initiated by the interaction of integrins with specific protein tyrosine kinases and phosphatases. One current challenge is to integrate the wealth of information obtained from studies of human blood and vascular cells with that obtained from their gene-targeted murine counterparts and from other eukaryotic model systems to yield a complete understanding of the protein-protein interactions involved in adhesive signaling.

Track(s):
MCB
Molecular Pharmacology

BMS Focus Areas:
Cancer Biology