Prof Jan (J. J.) Voorberg PhD

Training

Molecular and cell biology

Research interests

Biology of factor VIII and von Willebrand factor (VWF). VWF is synthesized by megakaryocytes and vascular endothelial cells where it is stored in specific organelles designated Weibel-Palade bodies. Following stimulation of endothelial cell with agonists that induce either a rise in cAMP or intracellular Ca2+, Weibel-Palade bodies release their content into the circulation thereby altering the local micro-environment within the vasculature. Regulated release of Weibel-Palade bodies allows for rapid responses to vascular perturbation. Current research focuses on the molecular mechanism involved in regulated release of inflammatory and haemostatic components from this intracellular storage pool. Following its release from vascular endothelium polymeric VWF is rapidly processed by the metalloprotease ADAMTS13. Ultra large VWF polymers have been found in the circulation of patients with acquired thrombotic thrombocytopenic purpura (TTP) which is due to the presence of inhibitory antibodies directed towards ADAMTS13. The characteristics of these antibodies are currently being addressed at the molecular level using phage display of antibody libraries. Related to this line of research are ongoing investigations into the mechanisms that underlie the development of inhibitory antibodies to blood coagulation factor VIII in patients with the bleeding disorder hemophilia A.

Technology

• Endothelial cell biology
• Confocal microscopy
• Phage display
• Human antibodies

Resume

2012-present	Prof of Cellular Hemostasis, University of Amsterdam, The Netherlands
2004-present	Staff member Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands
2003	Sabbatical leave Department of Medicine, University of Minnesota, Minneapolis, USA
1991-2003	Staff member Department of Plasma Proteins, Sanquin Research, Amsterdam, The Netherlands
1987-1991	PhD student at Department of Molecular Biology, CLB, Amsterdam, The Netherlands