Research Interests of Principal Investigator Dr. Nigel Key
As the Director of the UNC Blood Research Center, Dr. Key is an active clinician with a primary interest in disorders of thrombosis and hemostasis. The Key laboratory strives to develop and implement novel blood-based biomarkers to aid in the diagnosis and care of patients with disorders involving the coagulation system, both hemorrhagic and thrombotic.
For many years, we have been interested in the procoagulant properties of cells and cellular components (including extracellular vesicles and neutrophil-derived NETs) that interact with coagulation factors and lead to thrombin generation. We were the first to show the presence of circulating tissue factor in human sickle cell disease at a time when the presence of bioactive tissue factor in blood had not been established (Key NS, Blood 1998). We went on to develop the first described assay for the quantification of circulating microvesicle-associated tissue factor procoagulant activity in plasma using the human endotoxemia model (Aras O, Blood 2004). Most recently, we described a novel pathway of factor IX activation in the red cell storage lesion mediated by red cell-derived microvesicles (Noubouossie D, Blood 2020).
A second objective of the Key lab research program is to study fibrinolytic activity and hemostatic balance in different pathological contexts, including sickle cell disease, cancer and trauma. We developed and described plasma assays that detect global hypo- and hyper-fibrinolysis phenotypes. Our goal is to improve our understanding of the impact of the fibrinolytic system in several disease states.
A third major aim of the lab is to better understand the role and mechanisms of contact pathway activation in a variety of disease states. Measuring in vivo activation of the contact system is challenging because of the potential for artifactual ex vivo activation of contact factors that may confound assay interpretation. We recently developed a panel of robust enzyme-linked immunosorbent assays that can be used for sensitive and specific quantification of levels of activated enzymes of the contact system and intrinsic (factors XII, XI, IX and prekalllikrein) in complex with their cognate serpin inhibitors in plasma. These assays have allowed us to assess contact and intrinsic pathway activation in disorders of hemostasis and thrombosis, including sickle cell disease, red cell storage lesion, acute liver failure and trauma.