The overall goal of this Program Project is to understand how the processes of coagulation, thrombosis and fibrinolysis are initiated, regulated and terminated. This goal includes obtaining a fundamental understanding of the interrelationships between these processes, and ultimately obtaining the means to rationally manipulate them for diagnostic and therapeutic purposes. One of the concepts that has become increasingly clear is that much of the regulation of coagulation and fibrinolysis takes place through the assembly of macromolecular complexes on membrane and fibrin surfaces. Therefore, while we will study the functional properties of individual molecules, our emphasis is on those characteristics which pertain to the regulation of that molecule's function. This approach includes studies of macromolecular assemblies utilizing model systems such as synthetic vesicles, as well as platelets, fibrin and endothelial cells. There are also studies aimed at determining those characteristics of the vitamin K- dependent coagulation factors which result in regulation of expression at the level of carboxylation and thus the membrane binding phenomenon. The composite of the four projects and the two cores of this program will lead to detailed investigations of surface dependent reactions specific in thrombosis and thrombolysis, however, the principles discovered have ubiquitous applications in biology.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Research Review Committee B (HLBB)
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University of Vermont & St Agric College
Schools of Medicine
United States
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Kusak, Piotr; Czarnecka, Danuta; Gissel, Matthew et al. (2016) Activated factor IX, factor XI and tissue factor identify patients with permanent atrial fibrillation treated with warfarin who are at risk of ischemic stroke. Arch Med Sci 12:1000-1007
Bouchard, Beth A; Chapin, John; Brummel-Ziedins, Kathleen E et al. (2015) Platelets and platelet-derived factor Va confer hemostatic competence in complete factor V deficiency. Blood 125:3647-50
Brummel-Ziedins, Kathleen E; Everse, Stephen J; Mann, Kenneth G et al. (2014) Modeling thrombin generation: plasma composition based approach. J Thromb Thrombolysis 37:32-44
Bouchard, Beth A; Gissel, Matthew T; Whelihan, Matthew F et al. (2014) Platelets do not express the oxidized or reduced forms of tissue factor. Biochim Biophys Acta 1840:1188-93
de Haan, Hugoline G; Bezemer, Irene D; Vossen, Carla Y et al. (2014) Genetic variants in Cell Adhesion Molecule 1 (CADM1): a validation study of a novel endothelial cell venous thrombosis risk factor. Thromb Res 134:1186-92
Undas, A; Brummel-Ziedins, K E; Mann, K G (2014) Anticoagulant effects of statins and their clinical implications. Thromb Haemost 111:392-400
Whelihan, Matthew F; Kiankhooy, Armin; Brummel-Ziedins, Kathleen E (2014) Thrombin generation and fibrin clot formation under hypothermic conditions: an in vitro evaluation of tissue factor initiated whole blood coagulation. J Crit Care 29:24-30
Baker, Jason V; Brummel-Ziedins, Kathleen; Neuhaus, Jacqueline et al. (2013) HIV replication alters the composition of extrinsic pathway coagulation factors and increases thrombin generation. J Am Heart Assoc 2:e000264
Butenas, Saulius (2013) Comparison of natural and recombinant tissue factor proteins: new insights. Biol Chem 394:819-29
Whelihan, Matthew F; Mann, Kenneth G (2013) The role of the red cell membrane in thrombin generation. Thromb Res 131:377-82

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