Donna Woulfe, Ph.D.

Teaching

BISC667 Fundamentals of Pharmacology

BISC850 Functions of Microparticles

BISC403 Genetic and Evolutionary Biology

 

Research Interests

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. We have more recently shown that the Akt substrate, Glycogen synthase kinase (GSK)3beta, is also a regulator of platelet signaling and thrombosis. In contrast to Akt2-/- mice, platelets from mice lacking one allele of GSK3beta are hyperresponsive to agonists and the mice are more susceptible to thrombosis than their wildtype counterparts. Ongoing research in the laboratory is on understanding new pathways that regulate Akt and GSK3 signaling in platelets, including the role of arrestin-2 in platelet signaling and function. We also have new collaborative projects centered on understanding the influence of hyperglycemia on platelet function in vitro and in vivo.

Selected Publications

Stolla, MC*, Li D, Lu L, and D.S. WoulfeEnhanced 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. WoulfeArrestin-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 DSPKD 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.

Assistant Professor

Phone: (302) 831-0850

Email: dswoulfe@udel.edu

Office: 329 Wolf Hall

Lab: 341 Wolf Hall

Education

  • B.S. - Bucknell University (Major: Biology, Minor: Biochemistry)
  • Ph.D. - University of Pennsylvania (Pharmacology)
  • Post-Doctoral Fellowship - University of Pennsylvania