Inappropriate platelet activation contributes to vascular diseases including stroke and myocardial ischemia. Our laboratory is focused on phospholipid signaling in platelets and its contribution to inappropriate platelet activation. Ongoing projects are directed at understanding the roles of pleckstrin and lipid kinases in platelets. Pleckstrin (p47) was once solely known as an early marker of platelet activation; more recently it has been noted to contain the prototypic Pleckstrin Homology motif. Over the past half dozen years, work derived from our laboratory has demonstrated that pleckstrin plays a dominant role in the reorganization of the platelet, and lymphocyte, cytoskeleton. Furthermore, our laboratory has established these effects are regulated by pleckstrin phosphorylation, require critical lipid-binding residues contained with the amino-terminal Pleckstrin Homology domain, and have implicated an effector for this process to be the small GTP-binding protein, Rac. Additional work from our laboratory has helped define the role of phospholipid kinases in the pathway that is initiated by G-protein coupled receptors and ultimately leads to actin reorganization. Our studies use molecular and cellular biologic techniques to examine blood cell biology, and involve expression mutagenesis, single cell microinjection, genetic library screening, and murine homologous gene targeting ("gene knock-out").