Our research laboratory focuses on the roles of the blood coagulation and fibrinolytic systems in vascular disease. We are interested in the molecular processes that determine acute thrombus formation after vascular injury, as well as those that regulate subsequent thrombolysis.
Blood flow in injured carotid artery and pharmacological thrombolysis. Red bar denotes period of arterial injury. Ten minutes after occlusion, heparin (Hep) and human plasminogen (Pg) were administered, and 10 minutes later tPA (100 µg • kg-1 • mL-1) was infused. Note cyclic flow variation immediately preceding complete occlusion and restoration of flow 14 minutes after tPA was begun.
We also are interested in how components of the blood clotting and fibrinolytic systems contribute to the pathogenesis of chronic vascular disorders, such as atherosclerosis and restenosis after percutaneous coronary interventions. We study these issues by a variety of experimental approaches, ranging from in vitro studies with purified proteins to intact animal studies. In particular, we rely heavily on murine models of vascular injury and thrombosis, since they enable us to examine the impact of specific genes on complex biologic processes within the living animal. We also are conducting human genetic studies. These projects address the role of plasminogen activator inhibitor-1 as a risk factor for myocardial infarction, and the molecular basis of the variable sensitivity of patients to anticoagulation with warfarin.Ongoing projects in the laboratory include:
- Role of leukocyte-derived tissue factor in thrombosis
- Role of plasminogen activator inhibitor-1 (PAI-1) in the proliferative response to vascular injury
- Mechanisms by which C-reactive protein (CRP) modulates thrombosis
- Role of heme oxygenase-1 in thrombosis
- Regulation of fibrinolysis by thrombin activatable fibrinolysis inhibitor (TAFI)
I moved my research laboratory to the University of Missouri-Columbia in November 2004, when I assumed the position of Director of the Division of Cardiology. I currently hold appointments as Professor in the Department of Internal Medicine and in the Department of Medical Physiology and Pharmacology. I am very excited about the outstanding research opportunities at Mizzou, and I look forward to expanding my research program here in Columbia.