The broad goal in my laboratory is to investigate crosstalk between coagulation and inflammation in animal models of disease. My primary interest is sickle cell disease, a blood disorder caused by a hemoglobin mutation that results in sickling of red blood cells. The primary complications of sickle cell disease are anemia and vaso-occlusive crisis (VOC), as well as chronic inflammation and coagulation activation. VOC is caused by the formation of multicellular aggregates between neutrophils, platelets, sickle red blood cells and the endothelium that is due, in part, to thrombin-dependent activation of protease activated receptor 1 (PAR-1).聽 We are currently investigating how biased agonism of PAR1 with activated protein C (APC) can beneficially influence vaso-occlusive crisis and other pathologies in sickle cell disease. We use a variety of tools, such as transgenic mice, clinically relevant pharmacologic inhibitors, and molecular and cellular biology techniques to study the role of coagulation proteases and protease activated receptors in health and disease.
