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We are investigating how the blood clotting cascade is regulated, with applications to thrombotic diseases, bleeding disorders, and inflammation. Many of our studies have focused on understanding the initiation phase of blood clotting, an event that takes place when the soluble plasma protein, factor VIIa (a serine protease), binds to the integral membrane protein, tissue factor (TF), on cell surfaces. In 2006, we discovered that polyphosphate (an inorganic polymer of phosphate present in many infectious microorganism and secreted by activated human platelets) is a novel modulator of the blood clotting cascade and may represent the long-sought (patho)physiologic activator of the contact pathway of blood coagulation.
Our current research efforts focus primarily on: (1) Understanding, with atomic-scale resolution, how blood clotting proteins interact with membrane surfaces and how these membrane binding events contribute so profoundly to catalysis; (2) Understanding the mechanisms by which polyphosphate modulates the clotting system in hemostasis, thrombosis and inflammation; and (3) Developing a new toolkit of methods to solve, at atomic resolution, the structure and dynamics of membrane lipids as they interact with membrane proteins and other biologically important ligands.
Our current research efforts focus primarily on: (1) Understanding, with atomic-scale resolution, how blood clotting proteins interact with membrane surfaces and how these membrane binding events contribute so profoundly to catalysis; (2) Understanding the mechanisms by which polyphosphate modulates the clotting system in hemostasis, thrombosis and inflammation; and (3) Developing a new toolkit of methods to solve, at atomic resolution, the structure and dynamics of membrane lipids as they interact with membrane proteins and other biologically important ligands.
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Journal of Thrombosis and Haemostasisno. 1 (2023): 1-1
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Research and Practice in Thrombosis and Haemostasis (2023): 100783-100783
Journal of thrombosis and haemostasis : JTHno. 4 (2023): 709-709
Nature communicationsno. 1 (2023): 2177-2177
Seminars in thrombosis and hemostasis (2023)
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Research and Practice in Thrombosis and Haemostasis (2023): 101317-101317
Journal of Thrombosis and Haemostasisno. 8 (2023): 2005-2006
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