Dr. Joel Moake specializes in hemostasis-thrombosis. 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 and organelle storage site for coagulation factor VIII (FVIII); (4) molecular interactions between VWF and complement; (5) molecular mechanisms initiating the intrinsic coagulation pathway on endothelial cell surfaces; and (6) the pathophysiology of thrombosis in the anti-protein/phospholipid syndrome.
In recognition of his research accomplishments, Dr. Moake is an elected member of the American Society for Clinical Investigation and the Association of American Physicians. He has been repeatedly listed in the Best Doctors in America, and is one of a small number of physician members of the American Institute for Medical and Biological Engineering.
Von Willebrand factor (VWF) (green) is a long, thin protein that promotes blood clot formation. One end of VWF stays anchored to the blood vessel wall, while the rest unfurls like a sticky streamer, attracting platelets. Image by Nancy Turner
M.D., Johns Hopkins University School of Medicine (1967)
B.A., Johns Hopkins University (1964)
Dr. Moake and his 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;
– Unusually large VWF (ULVWF) multimers secreted from endothelial cells are not processed properly, and cause systemic platelet aggregation, in TTP;
– 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;
– FVIII is predominantly produced in endothelial cells and stored (along with VWF) in Weibel-Palade bodies (2015); and
– The alternative complement pathway is initiated and amplified by C3 binding to ULVWF multimers secreted by, and anchored to, human endothelial cells. The latter discovery provided a molecular linkage between hemostasis-thrombosis and inflammation.
