We are interested in the molecular and biochemical mechanisms involved in the formation of blood clots. Coagulation occurs after cellular proteins are exposed to flowing blood. Exposure of these proteins triggers a series of enzymatic reactions that culminate in the production of thrombin. Thrombin then activates platelets and cleaves the plasma protein, fibrinogen, to fibrin, which polymerizes into a web-like mesh that reinforces the blood clot. Clot formation is dictated by proteins and cells found in the blood, cells lining the blood vessels, and the flow of blood through the vessels. To examine events leading to blood clot formation, we use a variety of assays that model blood coagulation in vivo. Using these assays, we can precisely control the levels of plasma proteins and cells, and correlate enzyme activity (thrombin) and functional effect (clot formation). Our approaches have revealed novel, clinically-important information about mechanisms that promote clot formation in hemostasis and thrombosis.
Some facts about thrombosis and bleeding:
- Complications of abnormal blood clotting are the number one killer of Americans today.
- Heart disease is the number one cause of death in American women - more than all forms of cancer and the next four leading causes of death combined.
- Recent estimates suggest that one in every two men and one in every 3 women aged 40 and under will develop coronary heart disease in their lifetime.
- Thrombosis is the most frequent cause of death in cancer patients.
- Severe bleeding complicates approximately 10% of open-heart surgeries.
- Annually there are over 1 million cases of bleeding in the US that are the primary cause of hospitalization.
- More people die of arterial thrombosis than from cancer; more people die from venous thrombosis than from accidents.