Donna Woulfe, Ph.D.

Contact Dr. Woulfe

1025 Walnut Street
Room 412
Philadelphia, PA 19107

(215) 503-5152
(215) 923-3836 fax

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. More recent studies showed 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. New collaborative projects center on understanding the influence of hyperglycemia on platelet function in vitro and in vivo.

Publications

Most recent Peer-reviewed Publications

1. Role of tumor suppressor p53 in megakaryopoiesis and platelet function
2. PKD is for dense granule secretion
3. Arrestin-2 differentially regulates PAR4 and ADP receptor signaling in platelets.
4. The kinetics of αIIbβ3 activation determines the size and stability of thrombi in mice: Implications for antiplatelet therapy
5. Akt signaling in platelets and thrombosis
6. A Syk inhibitor for sick platelets?
7. G-protein-coupled receptors as signaling targets for antiplatelet therapy.
8. GSK3beta is a negative regulator of platelet function and thrombosis.
9. Serglycin proteoglycan deletion induces defects in platelet aggregation and thrombus formation in mice.
10. Platelet G protein-coupled receptors in hemostasis and thrombosis
11. Eph kinases and ephrins support thrombus growth and stability by regulating integrin outside-in signaling in platelets
12. Signaling receptors on platelets and megakaryocytes.
13. Boundary events: Contact-dependent and contact-facilitated signaling between platelets
14. 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
15. Defects in secretion, aggregation, and thrombus formation in platelets from mice lacking Akt2
16. Contact-dependent signaling during the late events of platelet activation.
17. Signaling through Gi family members in platelets: Redundancy and specificity in the regulation of adenylyl cyclase and other effectors
18. Interactions between Eph kinases and ephrins provide a mechanism to support platelet aggregation once cell-to-cell contact has occurred
19. Activation of Rap1B by Gi family members in platelets
20. ADP and platelets: The end of the beginning

View All Publications