Grant: CIHR Fellowship

Von Willebrand Disease (VWD) is the most common inherited bleeding disorder characterized in humans. Patients with VWD have blood clots that do not form properly, which increases the risk for bleeding. Von Willebrand factor (VWF) is a protein in the blood that helps platelets bind to each other and to the blood vessel wall. VWF also binds and protects factor VIII (FVIII), a protein which helps blood clots to form. Some patients with VWD have decreased production of VWF or a VWF protein that does not function properly as a result of a mutation in the gene for VWF. Other patients diagnosed with VWD have low plasma levels of VWF or FVIII because of increase clearance or removal of VWF or FVIII from the plasma. We believe that mutations in the gene for VWF and the clearance receptor stabilin-2 can increase the clearance of VWF and FVIII and contribute to VWD. The purpose of our research is: (1) to characterize the ability of stabilin-2 to regulate the clearance of VWF; (2) to investigate how mutations in the VWF gene increase the rate of clearance of VWF; (3) to characterize how mutations in the VWF gene increase the rate of clearance of FVIII. These studies are important because they could help us better understand how VWF and FVIII are cleared from the blood, and identify new genetic causes responsible for VWD. These studies could improve the health of patients with VWD by helping to develop strategies that could reduce VWF and FVIII clearance.