About
Work in the laboratory is primarily focused on platelet biochemistry. Human platelets are anucleated cells in the blood that play a central role in hemostasis and thrombosis. Current studies are involved in defining the roles of three different platelet thrombin receptors in platelet aggregation. Turtle and avian blood which contain nucleated platelets (thrombocytes) are also being studied, relative to human platelets to ascertain evolutionary relationships.
1. I am studying platelet (PLT) biochemistry as it relates to PLT function in hemostasis. The effect and mechanism of action of extracellular adenosine triphosphate (ATP) on PLT function is studied.
2. We have demonstrated that there are three distinct thrombin receptors on human platelets: GPIb, PAR-1, PAR-4, and these respond differentially to different forms of thrombin. I am pursuing further studies on the mechanism, conditions, second messengers, and potential drugs that impact on these three thrombin pathways. Biological processes being studied include: inhibition and stimulation of PLT aggregation; G-protein involvement; second messenger production; Ca2+ mobilization; and phosphorylation of proteins. Analytical procedures required for these studies include: PAGE; western blotting detection with specific antibodies; autoradiography; PLT aggregation; Ca2+ fluorescence studies; deoxyribonucleic acid (DNA)purification; restriction endonucleases; southern blots; nick translation; DNA hybridization and agarase gel electrophoresis.
3. We are also studying the hemostatic pathways in sea turtles. We have found that their thrombocytes (nucleated platelet analogs) have some receptors that are similar in function to human platelet receptors and are lacking others. They have only the extrinsic coagulation pathway and lack the intrinsic pathway. Many of their coagulation factors can functionally replace the corresponding human factors. Research interests: Platelet biochemistry, platelet thrombin receptors
Ca+ Mobilization, Deoxyribonucleic Acid Cloning, Deoxyribonucleic Acid Sequencing, DNA Cloning, DNA Sequencing, Extracellular Adenosine Triphosphatase, Extracellular ATP, Glycoproteins, Hemostasis, Platelets, Receptor, Signal Transduction, Thrombin Receptors
Current anti-thrombotic/anti-platelet drugs used clinically have not fully solved the problem of cardiovascular disease processes which remain the leading cause of death among USA citizens. We have identified a unique in vitro model system employing specific inhibitors to assay alpha-,beta- and gamma-thrombins which act at specific platelet thrombin receptors. This model affords us the opportunity to screen new potential anti-thrombosis/anti-platelet drugs which may control the previously unknown thrombin pathways that we have uncovered.