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E. Donnall Thomas Lecture and Prize

Program: General Sessions
Monday, December 7, 2015: 9:00 AM-10:00 AM
Hall D, Level 2 (Orange County Convention Center)

Lecture Title:
Thiol Isomerases as Potential Regulators Controlling The Initiation of Thrombus Formation

Barbara C. Furie, PhD, Professor Emeritus, Harvard Medical School and Bruce Furie, MD, Beth Israel Deaconess Medical Center, Harvard Medical School

No relevant conflicts of interest to declare.

After vascular damage, thrombus formation maintains the integrity of a closed, high-pressure circulatory system by rapidly initiating events in the vessel wall and in the blood to seal the breach. In the absence of injury, these events remain quiescent to maintain patent blood vessels.

Over the past 50 years, much has been uncovered about the molecular and cellular basis of thrombus formation. Under normal conditions, thrombus formation must be limited to the area of injury and thrombi must not propagate systemically. While the tissue factor pathway inhibitor, the protein C system, and antithrombin are known to play a critical role in limiting thrombus formation, what regulates initiation of thrombus formation that is, what keeps the process of clot formation dormant under normal conditions remains poorly understood.

With the application of digital high-speed, multi-channel fluorescence microscopy in vivo, thrombus formation can be studied in a physiologically relevant redox environment. Drs. Barbara and Bruce Furie will discuss new understanding gleaned from experiments in a laser-induced mouse model showing that extracellular thiol isomerases, including protein disulfide isomerase, are required for platelet accumulation and fibrin generation during thrombus formation. They will present this finding that suggests, in contrast to previously recognized regulatory mechanisms that modulate thrombus propagation after thrombus formation, that the thiol isomerase system may serve as a regulator of thrombus formation.

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