Grant: Travel Awards - Institute Community Support

Hemophilia A is a common inherited bleeding disorder. Patients with hemophilia A have blood clots that do not form properly, which increases the risk for bleeding. Factor VIII (FVIII) is a protein that helps blood clots to form. Some patients with hemophilia A have decreased production of FVIII or a FVIII protein that does not function properly as a result of a mutation in the gene for FVIII. Other patients diagnosed with hemophilia A have low plasma levels of FVIII because of increase clearance or removal of FVIII from the plasma. However, mechanisms that regulate clearance of FVIII are largely unknown. In these studies, we investigate the role of CLEC4M, a cell surface receptor expressed in the liver, in regulating FVIII clearance. In these studies, we show that mice which express CLEC4M in their liver have decreased plasma levels of FVIII as compared with mice that do not express CLEC4M. We show that CLEC4M can bind to sugar molecules on the FVIII protein. We also show that CLEC4M expressing cells can internalize and break down FVIII protein. These studies are important because they could help us better understand how FVIII is cleared from the blood, and improve the health of patients with hemophilia A by helping to develop strategies that could reduce FVIII clearance.