The Camire Lab
Our laboratory is interested in the molecular and cellular processes that contribute to and regulate blood coagulation. This dynamic defense mechanism has a major impact on human health and disease as failure of this system to respond appropriately can lead to life-threatening bleeding or thrombosis. We are interested in questions related to the enzymology, biochemistry, and molecular genetics of enzyme complexes involved in blood coagulation. We use a combination of kinetic, biophysical and structural techniques in conjunction with the expression of well characterized recombinant blood clotting proteins to gain insight into how proteins involved in the production of thrombin assemble and function within macromolecular enzyme complexes. Furthermore, we also employ biological models to evaluate hemostasis in vivo and to investigate new therapies for treatment of bleeding disorders.
The Krish Lab
In one project, my colleagues and I are investigating the mechanism of TFPI-dependent regulation of factor Xa by the extrinsic pathway. This study also explores the significance of the regulation of factor Xa formation, the contributions of factor VIIa , and the kinetics of blood cleavages in the conversion of factor IX to IXa. In our study of prothrombin regulation, we are investigating membrane-dependent steps in the activation of prothrombin; the significance of membrane channeling in the kinetic mechanism of prothombinase assembly; and the consequences of activated protein C on the fate of thrombinase.
The Zheng Lab
We are investigating the ADAMTS13 domains required for substrate recognition and specificity, the cellular origin of ADAMTS13 biosynthesis, the polarity of ADAMTS13 secretion in vascular endothelial and epithelial cells the signals and mechanisms that direct ADAMTS13 sorting and secretion, and the effect of ADAMTS13 mutations in patients with congenital TTP on ADAMTS13 sorting or secretion. Recombinant DNA, protein engineering, expression and purification, cell culture, immunofluorescent and confocal microscopy, and various other biochemical and biophysical assays will be employed in the laboratory. The advancement in this area will not only provide more insight into understanding of pathogenesis of thrombotic thrombocytopenic purpura, but also better diagnostic and therapeutic tools for this fatal disease.