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Thomas Jefferson University - Donna Woulfe
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Donna Woulfe
Medicine
Thomas Jefferson University
Jefferson Medical College
Center for Translational Medicine
Assistant Professor
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Mailing Address
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Rm 412 College Bldg, 1025 Walnut St.
Philadelphia, Pennsylvania 19107
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Expertise and Research Interests
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My research interests focus primarily on the intracellular signaling mechanisms of platelet activation and how signaling in platelets contributes to thrombosis in vivo. Platelets normally circulate through the vasculature as small, discoid cells that become activated to initiate formation of the hemostatic plug at sites of vascular injury. Platelet plug formation is initiated when platelets are exposed to matrix components revealed beneath the damaged endothelium, is extended by soluble mediators that recruit additional platelets to the growing platelet plug, and is stabilized by contact-dependent signals to prevent dissolution of the plug. Each step in the generation of the platelet plug is supported by intracellular signals.
Agonists that extend formation of the platelet plug generally bind to G protein-coupled receptors on the platelet surface. My previous studies have focused on how platelets become activated by agonists that bind to G protein-coupled receptors. In particular, we have shown that a novel Gi-mediated pathway in platelets leads to activation of the Ras family member, Rap1, a small GTPase that has been shown to regulate activation of the platelet integrin aIIbb3. Continued studies are aimed at identifying Rap1-interacting proteins that either 1) directly regulate Rap1 activation or 2) serve as novel effectors of Rap1 in platelets.
My most recent studies have focused on the later events in platelet signaling that stabilize platelet aggregates as they grow and contribute to stability of the platelet plug in vivo. I have shown 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 formationii. Akt2-/- mice are also resistant to thrombosis in an arterial injury model. Initial studies suggest that one candidate effector of Akt in platelets is GSK3b. There may be others. Some of the questions we are trying to answer include: 1) How does reduced expression of GSK3b affect platelet function? 2) How is GSK3b regulated in platelets? 3) Does expression of Akt or GSK3b affect activation of integrin aIIbb3? 4) Do these pathways affect phosphorylation of the integrin tail or enhance platelet secretion? 5) Can we identify additional effectors of Akt in platelets?
Understanding these and other pathways that regulate platelet activation and platelet plug stability may help us to identify novel targets for the development of therapies for thrombotic disorders leading to heart attacks and strokes.
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Publications
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- Woulfe D, Jiang H, Morgans A, Monks R, Birnbaum M, and Brass LF. Defects in secretion, aggregation, and thrombus formation in platelets from mice lacking Akt2. J Clin Invest. 2004 Feb;113(3):441-50.
- Prevost N, Woulfe DS, Tognolini M, Tanaka T, Jian W, Fortna RR, Jiang H, and Brass LF. 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 . 2004 Feb 15;103(4):1348-55.
- Prevost N, Woulfe D, Tognolini M, and Brass LF. Contact-dependent signaling during the late events of platelet activation. J Thromb Haemost. 2003 Jul;1(7):1613-27.
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Individual Expertise profile of
Donna Woulfe, Copyright © Donna Woulfe.
Last Updated
: Friday, January 7, 2005 4:14:31 PM
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