This program is devoted to understanding the way in which blood coagulation is initiated when blood contacts damaged tissues. In general, it is thought that the mechanism involves the formation of a complex between tissue factor, a specific glycoprotein found on many cell types, and factor VII, a protein that circulates in the blood. In project 1, we will be focussing on the mechanisms and kinetics of this interaction both in traditional, static systems, and an """"""""open"""""""" flow system developed in our laboratory. In project 2, measurements of this interaction will be made utilizing fluorescence and other biophysical techniques. In project 3, we will be studying the regulation of the tissue factor gene in vascular tissue. In project 4, the kinetics of feed-back regulation on the tissue factor pathway of coagulation will be studied. Project 5 is devoted to the flow reactor with a special emphasis on flow profiles. Here, both experimental data and computer simulation of laminar flow and disturbed flow will be evaluated. In project 6, the emphasis will be on producing mutations in the tissue factor protein that will be used for structure/function studies in the other projects. Taken together, these projects will enable us to describe this important initiation reaction in terms of the physical chemistry, biochemistry, genetics and regulation.
| Hathcock, James; Rusinova, Elena; Vaananen, Heikki et al. (2007) Lipid-bound factor Xa regulates tissue factor activity. Biochemistry 46:6134-40 |
| Jesty, Jolyon; Rodriguez, Jose; Beltrami, Edward (2005) Demonstration of a threshold response in a proteolytic feedback system: control of the autoactivation of factor XII. Pathophysiol Haemost Thromb 34:71-9 |
| Song, Xu; Sui, Aiwei; Garen, Alan (2004) Binding of mouse VL30 retrotransposon RNA to PSF protein induces genes repressed by PSF: effects on steroidogenesis and oncogenesis. Proc Natl Acad Sci U S A 101:621-6 |
| Hathcock, James J; Nemerson, Yale (2004) Platelet deposition inhibits tissue factor activity: in vitro clots are impermeable to factor Xa. Blood 104:123-7 |
| Schecter, Alison D; Berman, Adriane B; Yi, Lin et al. (2004) MCP-1-dependent signaling in CCR2(-/-) aortic smooth muscle cells. J Leukoc Biol 75:1079-85 |
| Kim, William J H; Chereshnev, Igor; Gazdoiu, Mihaela et al. (2003) MCP-1 deficiency is associated with reduced intimal hyperplasia after arterial injury. Biochem Biophys Res Commun 310:936-42 |
| Schecter, Alison D; Berman, Adriane B; Taubman, Mark B (2003) Chemokine receptors in vascular smooth muscle. Microcirculation 10:265-72 |
| Feinstein, Efraim; Deikus, Gintaras; Rusinova, Elena et al. (2003) Constrained analysis of fluorescence anisotropy decay:application to experimental protein dynamics. Biophys J 84:599-611 |
| Simon-Lukasik, Kristine V; Persikov, Anton V; Brodsky, Barbara et al. (2003) Fluorescence determination of tryptophan side-chain accessibility and dynamics in triple-helical collagen-like peptides. Biophys J 84:501-8 |
| Roque, Merce; Kim, William J H; Gazdoin, Michaela et al. (2002) CCR2 deficiency decreases intimal hyperplasia after arterial injury. Arterioscler Thromb Vasc Biol 22:554-9 |
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