His general area of research focuses on how the active enzyme species generated during the blood coagulation process are regulated by both specific protease inhibitors present in blood, by cell-dependent processes or by various pharmacologic agents designed to suppress blood clot formation and propagation. The experimental approaches include studies in phlebotomy blood and reaction systems constructed with varying ensembles of purified proteins. The overall goal is to delineate the sequence of pro and anticoagulant events that allow the blood coagulation system to form a barrier that plug leaks in a vessel without blocking flow through the vessel. The empirical results from these studies and those from other laboratories are then translated into the existing reaction pathway framework of a mathematical model of coagulation developed by the Mann laboratory. Expansion of the reaction pathways encompassed by this model to facilitate interpretation and design of empirical studies, and transformation of this model into a research tool with clinical applicability are the long term goals of the modeling effort.

Dr. Thomas Orfeo