Paula B. Tracy, PhD
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Paula B. Tracy, PhDEducation:Graduate School Training:ResidencyFellowshipSpecialty:Biochemistry and Cell BiologyCertifications:Academic Appointments:Chair and Professor of Biochemistry Professor of Medicine Biography:Dr. Tracy has been a faculty member and member of the Thrombosis Research Center at the University of Vermont College of Medicine since 1985. She was Vice-Chair of Biochemistry, and Professor of Biochemistry and Medicine beginning in 1997 and has served as Interim Chair since 2005. Dr. Tracy serves on the editorial board of several journals related to hemostasis and thrombosis, has been a member of the National Institutes of Health Hematology peer-review study section for eight years, served as Chairperson of the Gordon Conference on Hemostasis in 1996, and is serving as the Program Chairperson (Basic Sciences) for the 22nd International Society of Thrombosis and Haemostasis in Boston, MA, July, 2009. As a result of her contributions to Hemostasis and Thrombosis research, Dr. Tracy received a “Special Recognition Award” presented by the American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology in 2001 and was named a University Scholar for 2003-2004 by the Graduate College at the University of Vermont. Major Research Interests:Dr. Tracy’s current research interests are focused on how platelets regulate blood clotting reactions. The principle objective of her laboratory is to develop a fundamental understanding of how platelets participate in and regulate the formation of the important bioregulatory molecule, thrombin. Thrombin generation is effected by a Ca2+-dependent, membrane-bound complex of the cofactor protein, factor Va, and the serine protease factor Xa. Efforts are focused in 3 distinct, yet interrelated areas. One specific goal is to provide a quantitative understanding of the integrally related kinetic and binding events regulating the functional interactions of factors Va and Xa with the platelet membrane surface. The platelet membrane receptors, the intracellular signaling pathways, and the enzymatic processes controlling these events are being identified with biochemical and molecular biological approaches. A second goal is to define how thrombin, once formed, interacts with platelet proteins to modulate its activity. The multiple interactions of thrombin with platelet membrane proteins and how they modulate thrombin-induced platelet activation is central to our studies because thrombin activation of platelets has a dramatic effect on the assembly and function of prothrombinase. The third major goal is to define how megakaryocytes, platelet progenitor cells, developmentally regulate the endocytosis of the required cofactor factor V(a) and, to determine the cellular events regulating its endocytosis, its intracellular trafficking to storage granules and the phenotypic changes in the factor V molecule resulting from these interactions. Because the platelet-derived factor Va pool is essential for normal blood clotting, defining how platelets acquire this essential protein, process it, and express it at their membrane surface is key in regulating thrombin generation. The formation of thrombin at the surface of platelets is pivotal to the physiological and pathophysiological functions they provide as they localize to injured vascular tissue. Current Grant Support Grant Title: Regulation of Plasma Factor V Endocytosis by Megakaryocytes Grant Title: Surface Dependent Reactions in Thrombosis & Thrombolysis Grant Title: Hemostasis & Thrombosis Program for Trainees Publications:Representative Publications from a Total of 89 Camire RM, Pollak ES, Kaushansky K and Tracy PB: Secretable human platelet-derived factor V originates from the plasma pool (1998). Blood 92:3035-3041. Bouchard BA, Silveira JR and Tracy PB: On the role of EPR-1 or an EPR-1-like molecule in regulating factor Xa incorporation into Prothrombinase (2001). Thromb Haemost. 86:1133-1134. Bouchard BA and Tracy PB: Platelet regulation of thrombin generation in cardiovascular disease (Invited Review) (2001). Ital. Heart J. 2:819-823. Silveira JR, Kalafatis M and Tracy PB: Carbohydrate moieties on the procofactor factor V, but not the derived cofactor factor Va, regulate its inactivation by activated protein C (2002). Biochemistry 41:1672-1680. Tracy PB: Role of platelets and leukocytes in coagulation. In: Hemostasis and Thrombosis: Basic Principles and Clinical Practice, 4th edition. RW Colman, J Hirsh, VJ Marder, AW Clowes and JN George, eds. Lippincott-Raven Publishers, Philadelphia, PA , pp 576-596 (2001). Gould WR, Silveira JR, Tracy PB: Unique in vivo modifications of coagulation factor V produce a physically and functionally distinct platelet-derived cofactor: Characterization of purified platelet-derived factor V/Va (2004). J Biol Chem 279:2383-2393. Gould WR, Simioni P, Silveira JR, Tormene D, Kalafatis M, Tracy PB: Megakaryocytes endocytose and subsequently modify human factor V in vivo to form the entire pool of a unique platelet-derived cofactor (2005). J Thromb Haemost 3:450-456. Bouchard BA, Williams JL, Meisler NT, Long MW, Tracy PB: Endocytosis of plasma-derived factor V by megakaryocytes occurs via a clathrin-dependent, specific membrane binding event (2005). J Thromb Haemost 3:541-551. Bouchard BA, Meisler NT, Nesheim ME, Liu C-X, Strickland DK, Tracy PB: A unique function for LRP-1: A component of a two-receptor system mediating specific endocytosis of plasma-derived factor V by megakaryocytes (2008). J Thromb Haemost 6:638-644. Kleiman NS, Freedman J, Tracy PB, Furie BC, Bray PF, Phillips DR, Storey RF, Rusconi CP, French PA, Steinbuhl SR, Becker RC: Platelets: Developmental biology, physiology and translatable platforms for preclinical investigation and drug development (2008). Platelets 19:239-251. |
