"Regulation of von Willebrand Factor Function by Lipoproteins: Implications for the Thrombotic Microangiopathies and Sickle Cell Disease"

Abstract: Von Willebrand factor (VWF) is the largest protein in the blood, where it circulates as a series of disulfide-linked multimers. Its function is regulated by hydrodynamic flow. Under elevated shear stress or flow acceleration VWF unfolds to reveal previously cryptic sites for platelet binding, cleavage by the plasma metalloprotease ADAMTS13, and self-association sites through which the already massive protein forms even larger structures. These structures include fibers capable of spanning the lumens of blood vessels with diameters up to 300 µm. The fibers are very efficient at capturing platelets from the flowing blood. We recently found that VWF self-association process is regulated by plasma lipoproteins. High-density lipoprotein (HDL) inhibits VWF self-association whereas low-density lipoprotein (LDL) enhances selfassociation. The overall impact of the lipoproteins depends on the ratio of their concentrations. In this talk, I will explore our studies of VWF self-association and its mechanical and biochemical consequences in addition to the physiological and medical implications of its regulation by plasma lipoproteins. These will include studies on thrombotic microangiopathies and the vaso-occlusive process in sickle cell disease.

Speaker Bio

José López, MD is a native of New Mexico, where he attended college and medical school before moving to Seattle for residency, specialty training in hematology, and laboratory training in biochemistry at the University of Washington.

Dr. López’ first faculty position was with the Gladstone Institute for Cardiovascular Disease and the University of California, San Francisco, after which he moved to the Baylor College of Medicine, where he became Professor of Medicine and Vice Chair of Medicine for Research. In 2006, he was recruited back to Seattle to head the research program at Puget Sound Blood Center, now Bloodworks Northwest. Throughout his career, Dr. López’ research has focused on the mechanisms of platelet attachment to injured and normal blood vessels and the diseases that involve this process, which include bleeding diseases such as von Willebrand disease and clotting diseases such as thrombotic thrombocytopenic purpura, heart attack, and stroke. His research program has received continuous NIH funding since he established his laboratory.

Dr. López has twice served as a regular member of National Institutes of Health (NIH) study sections and has been Associate Editor for the journals Circulation and Blood and recently finished a term on the Council of the International Society on Thrombosis and Haemostasis. Dr. López has participated in numerous other activities for the scientific community including serving on the Council for the Center of Scientific Review of the NIH and on the Board of Scientific Counselors, also at NIH. He is Professor of Medicine at the University of Washington and is Adjunct Professor in the Departments of Biochemistry, Mechanical Engineering, and Pathology.