William P. Fay
Professor of Medicine and Medical Pharmacology & Physiology
EDUCATION/TRAINING
INSTITUTION AND LOCATION DEGREE
University of Illinois, Urbana, IL B.S. 1978 Biology
University of Illinois, Chicago, IL M.D. 1982 Medicine
Positions/Employment
1990-1993 Instructor of Internal Medicine (Cardiology), University of Michigan
1993-1998 Assistant Professor of Internal Medicine, University of Michigan
1998-2004 Associate Professor of Internal Medicine, University of Michigan
2004-pres. Professor of Internal Medicine, Cardiology Division Director, University of Missouri-Columbia
Memberships and Honors
1978 B.S. Magna Cum Laude, University of Illinois
1980 Phi Beta Kappa, University of Illinois
1981 Alpha Omega Alpha, University of Illinois
1982 Finalist, William J. Grove Award (Outstanding Graduate), University of Illinois
1989 Finalist, Young Investigator's Award Competition, American College of Cardiology
1990 Outstanding Research Award for Cardiovascular Trainees, Mayo Clinic
1992 Winner, Young Investigator Prizes in Thrombosis, American Heart Association
1992- Fellow, American College of Cardiology
1994 ACC/ESC Academic Exchange Award
1998 Finalist, Update in Thrombolysis 1998 Research Award Competition
2001- Fellow, American Heart Association
2004- J.W. and Lois Winifred Stafford Distinguished Chair in Diabetes and Cardiovascular Research, University of Missouri
2006 Thrombosis Special Recognition Award, ATVB Council of AHA
2006 Co-Chair, Annual Scientific Meeting, ATVB Council of AHA
2007- Editorial Board, ATVB Journal
2007- Member, National Research Committee, AHA
2007 Co-Chair, Annual Scientific Meeting, ATVB Council of AHA
2008 Chair, Annual Scientific Meeting, ATVB Council of AHA
Selected Peer-Reviewed Publications
1. Fay WP, Shapiro AD, Shih JL, Schleef RR, and Ginsburg D: Complete deficiency of plasminogen-activator inhibitor type 1 due to a frame-shift mutation. N. Engl. J. Med. 1992;327:1729-1733.
2. Fay WP, Eitzman DT, Shapiro AD, Madison EL, and Ginsburg D: Platelets inhibit fibrinolysis in vitro by both plasminogen activator inhibitor-1 dependent and independent mechanisms. Blood 1994;83:351-356.
3. Eitzman DT, Schwartz RS, Saggin L, Chi L, Lucchesi BR, and Fay WP: Heparin neutralization by platelet-rich thrombi: Role of platelet factor 4. Circulation 1994;89:1523-1529.
4. Eitzman DT, Fay WP, Lawrence DA, Francis-Chmura AM, Shore JD, Olson ST, and Ginsburg D: Peptide-mediated inhibition of platelet and recombinant plasminogen activator inhibitor-1 in vitro. J. Clin. Invest. 1995;95:2416-2420.
5. Fay WP, Murphy JG, and Owen WG: High concentrations of active plasminogen activator inhibitor-1 in porcine coronary artery thrombi. Arterioscler Thromb Vasc Biol. 1996; 16:1277-1284.
6. Fay WP, Parker AC, Condery L, and Shapiro AD: Human plasminogen activator inhibitor-1 (PAI-1) deficiency: Characterization of a large kindred with a null mutation in the PAI-1 gene. Blood 1997;90:204-208.
7. Farrehi PM, Ozaki CK, Carmeliet P, and Fay WP: Regulation of arterial thrombolysis by plasminogen activator inhibitor-1 in mice. Circulation 1998;97:1002-1008.
8. Fay WP and Bokka L: Functional analysis of the amino and carboxyl termini of streptokinase. Thromb. Haemost. 1998;79:985-991.Fay WP and Parker AC: Effects of radiographic contrast agents on thrombin formation and activity.Thromb Haemost. 1998;80:266-272.
9. Fay WP, Parker AC, Ansari MN, Zheng X, and Ginsburg D: Vitronectin inhibits the thrombotic response to arterial injury in mice. Blood 1999; 93:1825-1830.
10. Zhu Y, Carmeliet P, and Fay WP: Plasminogen activator inhibitor-1 is a major determinant of arterial thrombolysis resistance. Circulation 1999;99:3050-3055.
11. Boxrud PD, Fay WP, Bock PE: Streptokinase binds to human plasmin with high affinity, alters the plasmin active site environment, and induces changes in substrate specificity. J. Biol. Chem. 2000;275:14579-14589.
12. Zhu Y, Farrehi PM, Fay WP: Plasminogen activator inhibitor-1 enhances neointima formation after oxidative vascular injury in atherosclerosis-prone mice. Circulation 2001;103:3105-3110.
13. Boxrud PD, Verhamme IMA, Fay WP, Bock PE: Streptokinase triggers conformational activation of plasminogen through specific interactions of the amino-terminal sequence and stabilizes the active zymogen conformation. J Biol Chem 2001;276:26084-26089.
14. Nagashima M, Yin ZF, Zhao L, White K, Zhu Y, Lasky N, Broze GJ, Fay WP, Morser J: Thrombin-activatable fibrinolysis inhibitor (TAFI) deficiency is compatible with murine life. J. Clin. Invest. 2002;109:101-110.
15. Peng L, Bhatia N, Parker AC, Zhu Y, Fay WP: Endogenous vitronectin and plasminogen activator inhibitor-1 promote neointima formation in murine carotid arteries. Arterioscler Thromb Vasc Biol. 2002;22:934-939.
16. Zhu Y, Tomasiak R, Fay WP: Do Clinically-Relevant Circulating Concentrations of Radiographic Contrast Agents Inhibit Platelet-Dependent Arterial Thrombosis? Thromb Res. 2002;105:413-418.
17. 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.
18. 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.
19. Danenberg HD, Szalai, AJ, Swaminathan RV, Peng L, Chen Z, Sotomayor M, Seifert MS, Fay WP, Simon DI, Edelman ER: Increased arterial thrombosis following arterial injury in human C-reactive protein transgenic mice. Circulation 2003;108:512-515.
20. 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; J Inf Dis 2003; 188:497-505.
21. 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.
22. 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.
23. Rusconi CP, Roberts JD, Pitoc GA, Nimjee SM, White RR, Quick G, Fay WP, Sullenger BA: Antidote-mediated control of anticoagulant aptamer activity in vivo. Nature Biotechnology 2004;22:1423-1428.
24. Parker AC, Mundada LV, Schmaier AH, Fay WP: Factor VLeiden inhibits fibrinolysis in vivo. Circulation 2004;110:3594-3598.
25. Day SM, MD, Reeve JL, Pedersen, B, Farris DM, Myers DD, Im M, Wakefield TW, Mackman N, Fay WP: Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall. Blood 2005;105:192-198.
26. Filippov S, Koenig GC, Chun T-H, Hotary KB, Ota I, Bugge TH, Roberts JD, Fay WP, Birkedal-Hansen H, Holmbeck K, Sabeh F, Allen ED, Weiss SJ: MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells. J. Exp. Med. 2005; 202:663-671.
27. Tilley RE, Pedersen B, Pawlinski R, Sato Y, Shen Y, Erlich JH, Shen Y, Day S, Huang Y, Eitzman DE, Boisvert W, Curtiss LK, Fay WP, Mackman N: Atherosclerosis in mice is not affected by a reduction in tissue factor expression Arterioscler. Thromb. Vasc. Biol. 2006; 26:555-562.
28. Deerhake JP, Merz JC, Cooper JV, Eagle KA, Fay WP: The duration of anticoagulation bridging therapy in clinical practice may significantly exceed that observed in clinical trials. J Thromb Thrombolysis. 2007;23:107-113.
29. Meier DJ, Seva S, Fay WP: A comparison of anticoagulation results of patients managed with narrow vs. standard international normalized ratio target ranges. J Thromb Haemost. 2007;5:1332-1333.
30. Fay WP, Garg N, Sunkar M: Vascular functions of the plasminogen activation system. Arterioscler Thromb Vasc Biol 2007;27:1231-1237.
31. Kuchay SM, Kim N, Grunz EA, Fay WP, Chishti AH: Double knockouts reveal that protein tyrosine phosphatase 1B is a physiological target of calpain-1 in platelets. Molec Cell Biol 2007;27:6038-6052.
32. Ahmed A, Stephens JC, Kaus CA, Fay WP: Impact of preemptive warfarin dose reduction on anticoagulation after initiation of trimethoprim-sulfamethoxazole or levofloxacin. J Thromb Thrombolysis 2008;26:44-48.
33. Wu J, Stevenson MJ, Brown JM, Grunz EA, Strawn T, Fay WP: C-Reactive protein enhances tissue factor expression by vascular smooth muscle cells: Mechanisms and in vivo significance. Arterioscler Thromb Vasc Biol. 2008;28:698-704.
Research Support
Ongoing or approved for funding:
VA Merit Review Award PI: W. Fay, 30% effort
“C-Reactive Protein, Tissue Factor, and Thrombosis: Mechanisms and In Vivo Significance
4/1/07-3/31/10 (total direct costs $546,400 over 3 years of award)
The objectives are to determine the mechanisms by which CRP stimulates tissue factor expression and the in vivo significance of this pathwayMissouri Life Sciences Trust Fund
“Targeting Plasminogen Activator Inhibitor-1 to Inhibit Restenosis”
PI: W. Fay, 22% effort
01/01/09 – 12/31/11 (total direct costs $725,000 over 3 years of award)
The objective is to study effects of PAI-1 inhibitory compounds on restenosis in a porcine model.Recent:
““Molecular Genetics of Coagulation Disorders” PI: D. Ginsburg. W. Fay is Director of Project 4, “Regulation of Fibrinolysis at Sites of Arterial Injury.” 45% effort
Type: NIH/NHLBI Program Project Grant P01 HL57346
The objectives are to clarify the roles of PAI-1, vitronectin, and fibrinogen in regulating the proliferative response to arterial injury. 9/1/03-8/31/08 ($250,000 annual direct costs of Project 4)
Pending:
“Molecular Genetics of Coagulation Disorders” PI: D. Ginsburg
Dr. Fay is Co-Investigator (10% effort) on Project 3: (“Thrombosis and Hemostasis in Host Defense from Bacterial Infection”, PI: H. Sun). NIH/NHLBI Program Project Grant (competing renewal of P01 HL57346) The objectives are to generate and characterize inhibitors of streptokinase (SK) expression by group A streptococci (GAS) and examine the efficacy of SK expression inhibitors in a murine model of GAS infection.
4/1/09-3/31/14 ($223,863 annual direct costs of Project 3)
