Research of dr. Eric Huizinga: An essential first step in the arrest of bleeding is the adhesion of blood platelets to a damaged vessel wall.
In this process the large multimeric glycoprotein von Willebrand Factor (VWF) functions as a bridge between blood platelets and collagen fibers exposed at sites of vascular damage. A fascinating aspect of VWF is that it has no significant interaction with platelets in the absence of vascular damage, but binds platelets rapidly once VWF becomes immobilized at sites of vascular damage or is exposed to high shear stress. In a long-standing collaboration with the Thrombosis and Haemostasis Laboratory of the University Medical Center Utrecht we study the structural basis of von Willebrand factor mediated platelet adhesion. We solved the crystal structure of the collagen-binding A3 domain of von Willebrand factor and mapped the position of its collagen-binding site by a combination of co-crystallisation with an inhibiting antibody and site-directed mutagenesis.