Neuenschwander, Pierre, Ph.D.

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B.S. Chemistry (ACS), 1985, Rochester Institute of Technology.
Ph.D. Biochemistry & Molecular Biology, 1990, State University of New York at Stony Brook.

Research Interest:
Blood Coagulation

Current Projects:

  1. Regulation of factor VIII activation/inactivation by the factor VIIa-tissue factor complex.
  2. Enzymology of factor IXa, and roles of cofactors.

Lay Summary:
Blood clotting is necessary for maintaining life. However, certain life-threatening conditions (heart attacks and strokes) can result if clotting is not controlled. Two enzymes involved in clotting are factor VIIa (fVIIa) and factor IXa (fIXa). Both of these enzymes are always present in the circulation, but in an inert form. Clotting ensues only when damage to blood vessels causes a cofactor protein, tissue factor, to be exposed to the circulation thus binding to and "activating" fVIIa. Subsequently, another cofactor protein is also activated (fVIIIa) which binds to and "activates" fIXa. The two resulting enzyme-cofactor complexes (fVIIa-tissue factor and fIXa-fVIIIa) have each been implicated in thrombosis and other clotting diseases. Thus, the purpose of this research program is to characterize both of these "activation" events and elucidate the ability of both of these complexes to regulate clotting.

Research Overview:
The long-term goals of my research are to rigorously describe the molecular and kinetic mechanisms by which cofactors in blood coagulation exert themselves. The results are aimed at elucidating the ability of cofactors to effectively mediate the hemostatic response, as well as elucidating their roles in thrombosis. The results will not only enhance our understanding of these fundamental reactions in hemostasis, but will also enable the rational design of inhibitors for treatment of thrombotic disease. There are currently several areas of interest within my laboratory. Each of these areas involves understanding the roles of cofactors in the regulation of either of the two factor X activating complexes that are central in blood clotting; the factor VIIa-tissue factor complex and the factor IXa-factor VIIIa complex.

Selected Papers and Abstracts:

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