TISSUE FACTOR IN BLOOD COAGULATION

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.