The focus of our research is on the regulation of blood clotting, also called coagulation. This process is critical to life, as too little clot formation causes bleeding, while too much clot formation causes thrombotic events, such as heart attacks and strokes. We are particularly interested in anti-coagulant proteins, including Protein S (PS), Protein C (PC), and Tissue Factor Pathway Inhibitor (TFPI), which prevent thrombosis. We are also interested in the changes to the coagulation system that occur in different disease states, and how they contribute to the risk of thrombosis in patients. Our laboratory currently has three main areas of focus: 1. We are working to understand how PS, PC, and TFPI work together to control the coagulation process. We are using biochemical and structural biology approaches to understand how PS binds both PC and TFPI and to understand the effect of PS/PC function on PS/TFPI function, and vice versa. We have developed several novel reagents which allow us to independently study these proteins in complex systems, such as human plasma. 2. We are studying the changes in coagulation that occur in patients with Human Immunodeficiency Virus (HIV). Patients with HIV are at an increased risk of thrombosis, and this risk remains even after treatment with antiretroviral therapy. We have developed assays to measuring coagulation proteins in human plasma samples, and have shown that PS deficiency is common in this population. We are now collaborating with other laboratories across the College of Medicine to determine how PS deficiency develops, why it does not recover, and how PS deficiency may contribute to thrombotic risk. 3. Patients with Covid-19 are also at an increased risk of thrombosis. We are now characterizing the changes in coagulation that occur in these patients and are determining whether these changes, and the thrombotic risk, persist after patients have recovered from the virus.