Philip J. Fay, Ph.D.

Philip J. Fay, Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, NY 14642

Office: (585) 275-6576
Fax: (585) 473-4314

Research Bio

Factor VIII serves as a protein cofactor for the serine protease, factor IXa in the surface-dependent conversion of factor X to factor Xa during the blood coagulation cascade reactions. Deficiency or defects in factor VIII result in hemophilia A, the most common of the severe, inherited bleeding disorders. Ongoing studies in our laboratory include physical and biochemical analyses of factor VIII structure and inter-subunit interactions. We are particularly interested in study of the activated form of the cofactor, factor VIIIa, which consists of a labile heterotrimeric structure. Additional studies assess functional changes reflecting altered structure following interaction of factor VIII/factor VIIIa with effector molecules (serine proteases) such as thrombin and activated protein C.



The role of factor VIIIa is to increase the kcat of factor IXa by several orders of magnitude. Little is known about the mechanism by which this is achieved. A second major focus of our lab is to elucidate the molecular basis for the cofactor effect following reconstitution of the intrinsic factor Xase complex (factor IXa, factor VIIIa (or isolated subunits) plus phospholipid vesicles) using purified components.

These projects are complemented by the generation and analysis of recombinant proteins possessing point mutations at sites proposed to contribute to intra- and inter-protein interactions. Overall, our research program is aimed at gaining fundamental insights into the structure, activity and regulation of a protein central to hemostasis.

Recent Journal Articles

Showing the 5 most recent journal articles. 140 available »

2013 Jun 4
Wakabayashi H, Fay PJ. "Modification of interdomain interfaces within the A3C1C2 subunit of factor VIII affects its stability and activity." Biochemistry.. 2013 Jun 4; 52(22):3921-9. Epub 2013 May 21.
2013 Jun 1
Wakabayashi H, Fay PJ. "Molecular orientation of factor VIIIa on the phospholipid membrane surface determined by fluorescence resonance energy transfer." The Biochemical journal.. 2013 Jun 1; 452(2):293-301.
2013 Jun
Yada K, Nogami K, Wakabayashi H, Fay PJ, Shima M. "The mild phenotype in severe hemophilia A with Arg1781His mutation is associated with enhanced binding affinity of factor VIII for factor X." Thrombosis and haemostasis.. 2013 Jun; 109(6):1007-15. Epub 2013 Mar 07.
2013 May 24
Griffiths AE, Rydkin I, Fay PJ. "Factor VIIIa A2 subunit shows a high affinity interaction with factor IXa: contribution of A2 subunit residues 707-714 to the interaction with factor IXa." The Journal of biological chemistry.. 2013 May 24; 288(21):15057-64. Epub 2013 Apr 11.
2013 Apr 2
Takeyama M, Wintermute JM, Manithody C, Rezaie AR, Fay PJ. "Variable contributions of basic residues forming an APC exosite in the binding and inactivation of factor VIIIa." Biochemistry.. 2013 Apr 2; 52(13):2228-35. Epub 2013 Mar 22.

Current Appointments

Professor - Department of Biochemistry and Biophysics (SMD) - Primary

Education

PhD | Biochemistry | Univ Rochester Sch Med/Dent1982
MS | Molecular Biology | SUNY at Buffalo1977
BS | Microbiology | Ohio State Univ-Columbus1975