Gene targeting of Cdc42 GTPase inhibited filopodia and lamellipodia formation on immobilized collagen-related peptide.

Role and the mechanisms of action of Rho GTPases in regulation of platelet function

The long term objective of our research efforts is to better understand the biochemical mechanisms involved in the regulation of platelet function in hemostasis and thrombosis. We anticipate that a better understanding of these mechanisms will be helpful in delineating the signal(s) that may be targeted for the development of novel, safer and more effective antithrombotic agents.

We are investigating the roles of Rac1, Cdc42 and RhoA, small molecule GTP binding proteins belonging to the Rho family of GTPases, in regulation of platelet function using a dual approach of gene targeting Rho GTPases in mice and pharmacologically inhibiting Rho GTPases by rationally designed small molecule inhibitors that specifically inhibit Rac, Cdc42 and RhoA GTPases.

Anti-diabetic small molecules mimic the anti-platelet actions of insulin