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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL029019-18
Application #
6183611
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
1982-07-01
Project End
2003-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
18
Fiscal Year
2000
Total Cost
$1,876,636
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029
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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
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VanScyoc, Wendy S; Sorensen, Brenda R; Rusinova, Elena et al. (2002) Calcium binding to calmodulin mutants monitored by domain-specific intrinsic phenylalanine and tyrosine fluorescence. Biophys J 83:2767-80

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