Human Factor VIII Structure & Function
Technician Amy Griffiths working in the Fay Lab
Factor VIII serves as a protein cofactor for the serine protease, factor IXa in the membrane-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, inter-subunit interactions, and intermolecular interactions with other components of the clotting cascade. Overall, our research program is aimed at gaining fundamental insights into the structure, activity and regulation of a protein central to hemostasis. This information will have specific implications for understanding hemophilia A and developing superior therapeutics for its treatment.
- Cofactor Activity in Factor VIIIa of the Blood Clotting Pathway is Stabilized by an Interdomain Bond Between His 281 and Ser 524 Formed in Factor VIII. J Biol Chem. In press. (2014 Apr 01).
- Combining mutations that modulate inter-subunit interactions and proteolytic inactivation enhance the stability of factor VIIIa. Thromb Haemost. 112, . (2014 Mar 06).
- Residues flanking scissile bonds in Factor VIII modulate rates of cleavage and proteolytic activation catalyzed by Factor Xa. Biochemistry. 52, 8060-8. (2013 Nov 12).