Joel Moake MD

Joel Moake, MD, has done clinical and basic research in hemostasis-thrombosis for more than 40 years. His special interests have been: (1) shear stress-induced, von Willebrand factor (VWF)-mediated platelet adhesion/aggregation; (2) the pathophysiology and therapy of thrombotic thrombocytopenic purpura (TTP), the hemolytic-uremic syndromes (HUS), and other types of thrombotic microangiopathies; (3) the cellular site of production of coagulation factor VIII (FVIII) and other coagulation proteins; and (4) molecular interactions between VWF and the alternative complement pathway My research team was the first to determine that: high shear stress-induced platelet adhesion/aggregation requires large human VWF multimers, as well as platelet glycoproteins Ib and IIb-IIIa, adenosine diphosphate (ADP) and calcium (1986); ultra-large (or unusually large) VWF (ULVWF) multimers secreted from endothelial cells are not processed properly, and cause systemic platelet aggregation, in thrombotic thrombocytopenic purpura (TTP, 1982); inhibition of the VWF-cleaving protease, ADAMTS-13, by Shiga toxin contributes to ULVWF-mediated thrombosis in the microcirculation of the kidney in the common enterohaemorrhagic E. coli-associated type of HUS (2002); the alternative complement pathway is initiated and amplified by C3 binding to ULVWF multimers secreted by, and anchored to, human endothelial cells (2013; FVIII is produced and stored (along with VWF) in human endothelial cell Weibel-Palade bodies (2015); and, in addition to FVIII, other coagulation factors are predominantly produced in human endothelial cells (2019-20). The 2013 discovery provides a molecular linkage between hemostasis-thrombosis and inflammation. The 2015 and 2019-20 findings suggest a new mechanism for the activation of the intrinsic coagulation pathway on endothelial cell surfaces, and the activation of the extrinsic coagulation pathways on vascular fibroblasts.