Overview

The axis of the program is regulation of the hemostasis system, the surveillance system for vascular anomalies arising from injury, environmental input, or disease. The focal point is the protease thrombin, which regulates both the procoagulant and anticoagulant pathways of hemostasis.

Pathways under investigation include the Protease-Activated Receptor (PAR) assembly on platelets (thrombin is the protease), thrombin specificity, Ca(II)-mediated folding and membrane assembly of the thrombin zymogen prothrombin, microenvironmental regulation of thrombosis by sodium and calcium ions, the basis for individual propensity to thrombosis (thrombophilia), the impact of infection on thrombosis propensity, the relation of steroid hormones to vascular disease, development of diagnostic markers of pre-symptomatic ischemic vascular disease, extracorporeal thrombosis with model biomaterial systems, and the enzymology of the hemostasis system in vivo.

Special methodologies include biophysical measurements of protein structure, including analytical centrifugation for quaternary structure, fluorescence spectroscopy for folding reactions, isolated heart perfusion for endothelial biochemistry, and ultradilute platelet culture for platelet biochemistry and metabolism.