Background:

Dr. Tracy received her Ph.D. in Biology, with an emphasis in Biochemistry, from Syracuse University in 1977. Her current interests in how platelets regulate blood clotting reactions developed as a result of her 5 years of post-doctoral training in the Special Coagulation Laboratory, Division of Hematology at the Mayo Clinic in Rochester, MN. Her first university appointment was made in 1983 as an Assistant Professor of Pathology at the University of Rochester, Rochester, NY. In 1985, she moved to the University of Vermont as a Research Assistant Professor of Medicine and Biochemistry and member of the Thrombosis Research Center. She became a tenured Professor of Biochemistry in 1995, and in July 2005, accepted the position of Interim Chairperson of the department. In addition to her research activities and pre- and post-doctoral training activities, Dr. Tracy also has assumed a significant teaching role in the graduate and medical schools. She is a strong proponent of academia and thus spends her time between administration, research, teaching and mentoring her students. As a result of her research and training endeavors, Dr. Tracy serves on the editorial board of several journals related to hemostasis and thrombosis, was a member of the National Institutes of Health Hematology Study Section for eight years and served as Chairperson of several highly specialized meetings, such as the Gordon Research Conference on Hemostasis and the Federation of the American Society of Experimental Biologists Summer Research Conference on Proteases and Vascular Biology.

Research Interests:

Cell & Molecular Biology
Coagulation Biology & Disease
Enzymology
Structural Biology

Project Description:

The principle objective of our laboratory is to develop a fundamental understanding of how platelets participate in and regulate the formation of the important bioregulatory effector molecule, thrombin. Thrombin generation is effected by the macromolecular complex, Prothrombinase, which consists of a CaČ⁺-dependent, membrane-bound complex of the cofactor protein, factor Va, and the serine protease, factor Xa. One specific goal is to provide both a qualitative and quantitative understanding of the integrally related kinetic and binding events regulating the functional interactions of factors Va and Xa with the platelet membrane surface. A structural model of how Prothrombinase assembles on the activated platelet membrane is being determined using a cross-linking and proteomics approach. The membrane receptors, the intracellular signalling pathways and the enzymatic processes controlling these events are also being identified using biochemical and molecular biological approaches. A second major goal is to define how megakaryocytes, platelet progenitor cells, developmentally regulate the endocytosis and possible synthesis of the required cofactor factor V(a) and, to determine the cellular events regulating its intracellular trafficking to storage granules and the phenotypic changes in the factor V molecule resulting from these interactions. Since 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 to our understanding of how thrombin generation is regulated. The formation of thrombin at the surface of platelets is pivotal to the physiological and pathophysiological functions they provide as they localize to vascular and extravascular tissue sites.