William P. Fay, M.D.
Professor of Internal Medicine and Medical Pharmacology & PhysiologyOffice Location: 306 Cs&E
Office Phone: 882-2296
fayw@missouri.edu
Research Interests
• Role of leukocyte-derived tissue factor in thrombosis Techniques / Methodology: • Mouse gene targeting
• Role of plasminogen activator inhibitor-1 (PAI-1) in the proliferative response to vascular injury
• Mechanisms by which C-reactive protein (CRP) modulates thrombosis
• Role of heme oxygenase-1 in thrombosis
• Regulation of fibrinolysis by thrombin activatable fibrinolysis inhibitor (TAFI)
• Rodent models of human vascular disease
• Structure-function studies of blood coagulation proteins
• Thrombosis models
Research Description
Our research laboratory focuses on the roles of the blood coagulation and fibrinolytic systems in vascular disease. We are interested in the molecular processes that determine acute thrombus formation after vascular injury, as well as those that regulate subsequent thrombolysis. We also are interested in how components of the blood clotting and fibrinolytic systems contribute to the pathogenesis of chronic vascular disorders, such as atherosclerosis and restenosis after percutaneous coronary interventions. We study these issues by a variety of experimental approaches, ranging from in vitro studies with purified proteins to intact animal studies. In particular, we rely heavily on murine models of vascular injury and thrombosis, since they enable us to examine the impact of specific genes on complex biologic processes within the living animal. We also are conducting human genetic studies. These projects address the role of plasminogin activator inhibitor-1 as a risk factor for myocardial infarction, and the molecular basis of the variable sensitivity of patients to anticoagulation with warfarin.
Professional Background
- University of Illinois, B.S.
- University of Illinois, M.D.
- Residency in Internal Medicine, University of Michigan Medical Center
- Clinical and Research Fellowship in Cardiovascular Medicine, Mayo Clinic
- Postdoctoral Research Fellow, Howard Hughes Medical Institute
- Assistant Professor of Internal Medicine, University of Michigan
- Associate Professor of Internal Medicine, University of Michigan
Selected Publications
- Day SM, Duquaine D, Mundada LV, Menon RG, Khan BV, Rajagopalan S, Fay WP: Chronic iron administration increases vascular oxidative stress and accelerates arterial thrombosis. Circulation 2003; 107:2601-2606.
- Mundada LV, Prorok M, DeFord ME, Figuera M, Castellino FJ, Fay WP: Structure-function analysis of the streptokinase amino terminus (residues 1-59). J Biol Chem 2003; 278:24421-24427.
- Danenberg HD, Szalai, AJ, Swaminathan RV, Peng L, Chen Z, Seifert MS, Fay WP, Simon DI, Edelman ER: Increased thrombosis after arterial injury in human C-reactive protein-transgenic mice. Circulation 2003;108:512-515.
- Khil J, Im M, Heath A, Ringdahl U, Mundada L, Engleberg NC, Fay WP: Plasminogen enhances group A streptococcal virulence by streptokinase-dependent and streptokinase-independent mechanisms. J Inf Dis 2003; 188: 495-505.
- Peng L, Mundada L, Stomel JM, Liu JJ, Sun J, Yet S-F, Fay WP: Induction of heme oxygenase-1 expression inhibits platelet-dependent thrombosis. Antiox Redox Signal. 2004;6:729-735.
- Sun H, Ringdahl U, Homeister J, Fay WP, Engleberg C, Yang A, Wang X, Sjobring U, Ginsburg D: Plasminogen is a critical host pathogenicity factor for group A streptococcal infection. Science 2004;305:1283-1286.