This program is directed toward the detailed understanding of tissue factor, the central initiator of blood coagulation. Tissue factor, a transmembrane protein, functions as an essential activator of an enzyme and enzyme precursor that circulate in the blood, factors VIIa and VII. Together, the form a specific enzyme that starts the coagulation of blood by activating two other blood proteins. Recent evidence indicates that tissue factor is implicated not only in blood coagulation but also in thrombosis, which is a clot that forms inside a blood vessel. This problem is being approached using techniques involving computer simulations, physical chemistry, enzyme kinetics and molecular biology. A new finding suggests that tissue factor may also be involved in the spread of cancer. Accordingly, one project is designed to test this hypothesis by manipulating the tissue factor content of cells that in their native state are only slightly metastatic. We also are interested in the detailed structure of tissue factor in complex with the enzyme, factor VIIa and the next protein involved in the coagulation scheme, factor X. These projects involve research laboratories at Mt. Sinai School of Medicine and Yale University. There are four research teams in this program which are collaborating on a series of experiments that are intended to answer several fundamental questions regarding blood coagulation and thrombosis.
| 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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