- About Us
- Education & Advisement
- Our Research
- Our People
- News & Events
- Log in
Donna Woulfe, Ph.D.
BISC690 Fundamentals of Pharmacology
BISC850 Functions of Microparticles
BISC403 Genetic and Evolutionary Biology
Dr. Woulfe's research interests focus primarily on the intracellular signaling mechanisms of platelet activation and how signaling in platelets contributes to thrombosis in vivo. Agonists that extend formation of the platelet plug generally bind to G protein-coupled receptors on the platelet surface. Dr. Woulfe's previous studies have focused on how platelets become activated by agonists that bind to G protein-coupled receptors and how platelet signaling stabilizes platelet aggregates as they grow. A key finding from these studies was that platelets from mice lacking certain isoforms of the serine/threonine kinase Akt (particularly Akt2) have defects in platelet secretion, fibrinogen binding, and stable aggregate formation. Akt2-/- mice are also resistant to thrombosis in an arterial injury model. In contrast, the Akt substrate, Glycogen synthase kinase (GSK)3beta, is a negative regulator of platelet signaling and thrombosis. Platelets from mice lacking one allele of GSK3beta are hyperresponsive to agonists and the mice are more susceptible to thrombosis than their wildtype counterparts. We have more recently shown that arrestin-2 regulates the function of PI3K and Akt signaling and function in platelets and have new collaborative projects centered on understanding the influence of hyperglycemia/diabetes on platelet function in vitro and in vivo.
Our newest work focuses on understanding novel interactions of platelet surface molecules and how they contribute to platelet signaling and thrombosis. In this regard, we are focusing on the agonist-dependent interaction of the thrombin receptor PAR4 with the ADP receptor P2Y12. We are also working to understand the stoichiometry and function of P2Y12 in resting and activated platelets and how two mutations in P2Y12 identified in patients with bleeding disorders may alter the interactions of P2Y12 with itself, G protein, or other receptors. Finally, we are exploring the role of a novel Ca++-dependent Ca++ channel, termed TMEM16f or anoctamin 6, in the shedding of small platelet fragments called microparticles. Preliminary data suggest that these platelet-derived microparticles may contribute to thrombosis and understanding the mechanism by which pro-coagulant microparticles are generated may suggest novel ways to inhibit their generation, function and ultimately, reduce cardiovascular risk.
D.S. Woulfe. PMNs deliver first aid to clot. Blood 2014; 124 (16)2475.
Jiang J., Woulfe DS, Papoutsakis ET. Shear enhances thrombopoiesis and formation of micorparticles that induce megakaryoctyic differentiation of stem cells. Blood. 2014; 124(13)2094-103.
Khan A, Li D, Ibrahim S, Smyth E, Woulfe DS. The physical association of the P2Y12 receptor with PAR4 regulates arrestin-mediated Akt activation. Mol Pharmacol. 2014 Jul;86(1):1-11.
Lindsey S, Jiang J, Woulfe D, Papoutsakis ET. Platelets from mice lacking the aryl hydrocarbon receptor exhibit defective collagen-dependent signaling. J Thromb Haemost. 2014;12(3):383-94.
Stolla, MC*, Li D, Lu L, and D.S. Woulfe. Enhanced platelet activity and thrombosis in a murine model of Type I diabetes are partially IGF-1 and PI3K-dependent. Journal of Thrombosis and Haemostasis, 2013 May, 11(5):919-29.
Bynagari-Settipalli YS, Lakhani P, Jin J, Bhavaraju K, Rico MC, Kim S, Woulfe D., and Kunapuli SP. Protein Kinase C isoform epsilon negatively regulates ADP-induced calcium mobilization and thromboxane generation in platelets. Arterioscler Thromb Vasc Biol. 2012 May;32(5):1211-9.
Apostolidis, PA, Woulfe, D.S., Chavez M, Miller, WM, Papoutsakis, ET. Role of Tumor Suppressor p53 in Megakaryopoiesis and Platelet Function. Experimental Hematology, 2012 Feb;40(2):131-42.
Li, D., D'Angelo, L., Chavez, M. and D. S. Woulfe. Arrestin-2 differentially regulates PAR4 and ADP receptor signaling in platelets. J Biol Chem. 2011 Feb 4;286(5):3805-14.
Stolla, M., Stefanini, L., Roden, R.C., Chavez, M., Hirsch, J., Greene, TL., Ouellette, T.D., Maloney, L.F., Diamond, S.L., Poncz., M., Woulfe, D.S., and Bergmeier, W. The kinetics of aIIbb3 activation determines the size and stability of thrombi in mice: implications for antiplatelet therapy. Blood. 2011 Jan 20;117(3):1005-13.
Woulfe DS. PKD is for dense granule secretion. Blood. 118(2):220-2, 2011.
Woulfe, D.S. Akt signaling in platelets and thrombosis. Expert Review of Hematology. 3 (1): 81-91, 2010.
Woulfe, D.S. A Syk inhibitor for Sick Platelets? Blood. Apr 2;113(14):3133-4, 2009.
Smyth, S.S., Woulfe, D.S., Weitz, J.I., Gachet, C., Conley, P.B., Goodman, S.G., Roe, M.T., Kuliopulos, A., Moliterno, D.J., French, P.A., Steinhubl, S.R., and Becker R.C. G-Protein–Coupled Receptors as Signaling Targets for Antiplatelet Therapy. Arteriosclerosis, Thrombosis, and Vascular Biology. 29(4):449-57, 2009.
Li, D, August, S, and Woulfe, D.S. GSK3b is a Negative Regulator of Platelet Function and Thrombosis. Blood. 111(7):3522-30, 2008.
Woulfe D.S., Lilliendahl JK, August S, Rauova L, Kowalska MA, Abrink M, Pejler G, White JG, Schick BP. Serglycin proteoglycan deletion induces defects in platelet aggregation and thrombus formation in mice. Blood. 111(7):3458-67, 2008.
Prevost, N.*, Woulfe, D.S.*, Jiang, H., Stalker, T., Marchese, P., Ruggeri, Z.M., Jiang, H., and Brass, L.F. Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside-in signaling in platelets. Proc Natl Acad Sci U S A. 102(28):9820-5, 2005 (*co-first authors).
Woulfe. D.S. Platelet G protein-coupled receptors in hemostasis and thrombosis. J Thromb Haemost. 3(10):2193-200, 2005.
Woulfe, D.S., Jiang, H., Monks, B., Birnbaum, M. and Brass, L.F. Defects in secretion, aggregation, and thrombus formation in platelets from mice lacking Akt2. The J of Clinical Investigation, 113: 441-450, 2004.
Prevost, N.*, Woulfe, D.S.*, Tognolini, M., Tanaka, T., Jian, W., Fortna, R., Jiang, H., and Brass, L.F. Signaling by ephrinB1 and EphA4 in platelets promotes Rap1 activation, platelet adhesion and agregation via effector pathways that do not require phosphorylation of ephrinB1. Blood, 103(4):1348-55, 2004. (*co-first authors).
Yang, J., Wu, J., Jiang, H., Mortensen R., Austin, S., Manning, D.R., Woulfe, D., and Brass L.F. Signaling through Gi family members in platelets. Redundancy and specific regulation of adenylyl cyclase and other effectors. Journal of Biological Chemistry, 277(48):46035-42, 2002.
Prevost, N., Woulfe, D., Tanaka, T., and Brass, L.F. Interactions between Eph kinases and ephrins provide a mechanism to support platelet aggregation once cell-to-cell contact has occurred. Proc. Natl. Acad. Sciences USA, 99(14):9219-24, 2002.
Woulfe, D.S., Jiang, H., Yang, J., and Brass. L.F. Activation of Rap1B by Gi family members in human platelelets. Journal of Biological Chemistry, 277(26):23382-90, 2002.
O'Brien, P.J., Prevost, N., Molino, M., Holinger, M.K., Woolkalis, M.J., Woulfe, D.S., and Brass, L.F. Thrombin responses in human endothelial cells: contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1. J of Biological Chemistry, 275(18):13502-13509, 2000.
Woulfe, D.S. and Stadel, J.M. Structural Basis for the Selectivity of the RGS Protein, GAIP for Gai Family Members: Identification of a Single Amino Acid Determinant for Selective Interaction of Gai Subunits with GAIP. Journal of Biological Chemistry, 274(25):17718-17724, 1999.
Nakada, M.T., Tam, S.H., Woulfe, D.S., Casper K.A., Swerlick, R.A., and Ghrayeb, J.: Neutralization of TNF by the antibody cA2 reveals differential regulation of adhesion molecule expression on TNF-activated endothelial cells. Cell Adhesion and Communication 5(6):491-503, 1998.
Siegel, S.A., Shealy, D.J., Nakada, M.T., Le, J., Woulfe, D.S., Progert, L., Kollias, G., Ghrayeb, J., Vilcek, J., and Daddona, P.E.: The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo. Cytokine 7(1):15-25, 1995.
Phone: (302) 831-0850
Office: 329 Wolf Hall
Lab: 341 Wolf Hall
- B.S. - Bucknell University (Major: Biology, Minor: Biochemistry)
- Ph.D. - University of Pennsylvania (Pharmacology)
- Post-Doctoral Fellowship - University of Pennsylvania