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Most of the work we are currently doing is devoted to understanding the molecular basis for platelet activation in vivo. Individual projects are looking at the role of heterotrimeric G proteins in initiating platelet activation, low molecular weight GTP-binding proteins in fostering integrin activation, and Eph kinases in maintaining platelet activation. The actual studies are being done in vitro using isolated human platelets and transfected cell systems, and in vivo using genetically engineered mice. Selected Publications: Woulfe, D., H. Jiang, A. Morgans, R. Monks, M. Birnbaum, and L.F. Brass (2004) Defects in secretion, aggregation and thrombus formation in platelets from mice lacking Akt2. J. Clin. Invest. 113:4414-450. Prévost, N., D.S. Woulfe, M. Tognolini, T. Tanaka, W. Jian, R.R. Fortna, H. Jiang and L. F. Brass (2004) Signaling by ephrinB1 and Eph kinases in platelets promotes Rap1 activation, platelet adhesion and aggregation via effector pathways that do not require phosphorylation of ephrinB1. Blood 103:1348-1355. O'Brien, PJ, H. Koi, S. Parry, L.F. Brass, J.F. Strauss 3rd, L.P. Wang, J.E. Tomaszewski, L.K. Christenson (2003) Thrombin receptors and protease-activated receptor-2 in human placentation: receptor activation mediates extravillous trophoblast invasion in vitro. Am J Pathol. 163:1245-54. Yang, J., J. Wu, H. Jiang, R. Mortensen, S. Austin, D.R. Manning, D. Woulfe and L.F. Brass (2002) Signaling through Gi family members in platelets: redundancy and specificity in the regulation of adenylyl cyclase and other effectors. J. Biol. Chem. 277:46035-46042. Prevost, N., D. Woulfe, T. Tanaka and L.F. Brass (2002) Interactions between Eph kinases and ephrins provide a novel mechanism to support platelet aggregation once cell-to-cell contact has occurred. Proc. Nat. Acad. Sci 99:9219-9224. D. Woulfe, H. Jiang, R. Mortensen, J. Yang and L.F. Brass (2002) Activation of Rap1B by Gi family members in platelets. J. Biol. Chem. 277:23382-23390. |
