Donna Woulfe, Ph.D.

Contact Dr. Woulfe

Center for Translational Medicine
1025 Walnut Street, Suite 408
Philadelphia, PA 19107

(215) 503-5152
(215) 503-5731 fax

Degree
Ph.D., University of Pennsylvania, Philadelphia, PA, 1999

Post-doctoral Fellowship
University of Pennsylvania, Platelet Biochemistry

University Appointment
Research Associate, Department of Medicine, University of Pennsylvania School of Medicine, 2002-03
Assistant Professor of Medicine, Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, 2004-present
Assistant Professor, Molecular Physiology and Biophysics, Thomas Jefferson University, 2007-present

Research and Clinical 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.

Publications

Most Recent Peer-reviewed Publications

1. A Syk inhibitor for sick platelets?
2. G-protein-coupled receptors as signaling targets for antiplatelet therapy.
3. GSK3beta is a negative regulator of platelet function and thrombosis.
4. Serglycin proteoglycan deletion induces defects in platelet aggregation and thrombus formation in mice.
5. Platelet G protein-coupled receptors in hemostasis and thrombosis
6. Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside-in signaling in platelets
7. Signaling receptors on platelets and megakaryocytes.
8. Boundary events: Contact-dependent and contact-facilitated signaling between platelets
9. 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
10. Defects in secretion, aggregation, and thrombus formation in platelets from mice lacking Akt2
11. Contact-dependent signaling during the late events of platelet activation.
12. Signaling through Gi family members in platelets: Redundancy and specificity in the regulation of adenylyl cyclase and other effectors
13. Interactions between Eph kinases and ephrins provide a mechanism to support platelet aggregation once cell-to-cell contact has occurred
14. Activation of Rap1B by Gi family members in platelets
15. ADP and platelets: The end of the beginning
16. Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin- cleaved PAR1
17. Structural basis for the selectivity of the RGS protein, GAIP, for Gα(i) family members: Identification of a single amino acid determinant for selective interaction of Gα(i) subunits with GAIP
18. Neutralization of TNF by the Antibody cA2 Reveals Differential Regulation of Adhesion Molecule Expression on TNF-Activated Endothelial Cells
19. Somatostatin receptor activation of cellular effector systems
20. The mouse/human chimeric monoclonal antibody cA2 neutralizes TNF in vitro and protects transgenic mice from cachexia and TNF lethality in vivo