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Prof. PhD J.J. Voorberg

Position
Research Associate
Main activities
Education, Research
Specialisation
Cellular Hemostasis
Focus of research
Within my research group we explore cellular components that are involved in maintenance of vascular homeostasis. Our research on “Cellular Haemostasis” aims to integrate biochemical and clinical research in the area of thrombosis and hemostasis, vascular biology as well as molecular and cellular immunology. Through this approach we aim to increase our current knowledge on the interactions of hemostatic proteins with the vessel wall as well as the immune system. We expect that studies in this area will result in novel therapeutic approaches for patients with vascular or haematological disorders.

Our current focus of research comprises the composition and regulatory mechanism involved in release of Weibel-Palade bodies, intracellular reservoirs of hemostatic protein, angiogenic factors and inflammatory components. In related studies we aim to characterize endothelial cells derived of peripheral blood of patient with vascular or hematological abnormalities. An important topic for the next 5 years comprises the interaction of hemostatic proteins with the immune system. These studies are relevant for a better understanding of the factor contribution to inhibitor development of hemophilia A as well the auto-immune disorder thrombotic thrombocytopenic purpura (TTP).

Key publications
  • Sorvillo Nicoletta, van Haren Simon D., Kaijen Paul H., ten Brinke Anja, Fijnheer Rob, Meijer Alexander B., Voorberg Jan Preferential HLA-DRB1*11-dependent presentation of CUB2-derived peptides by ADAMTS13-pulsed dendritic cells Blood 2013;121 (17):3502-3510 [PubMed]
  • Herczenik Eszter, van Haren Simon D., Wroblewska Aleksandra, Kaijen Paul, van den Biggelaar Maartje, Meijer Alexander B., Martinez-Pomares Luisa, ten Brinke Anja, Voorberg Jan Uptake of blood coagulation factor VIII by dendritic cells is mediated via its C1 domain Journal of allergy and clinical immunology 2012;129 (2):501-U341 [PubMed]
  • Martin-Ramirez Javier, Hofman Menno, van den Biggelaar Maartje, Hebbel Robert P., Voorberg Jan Establishment of outgrowth endothelial cells from peripheral blood Nature protocols 2012;7 (9):1709-1715 [PubMed]
  • Verbij Fabian C., Turksma Annelies W., de Heij Femke, Kaijen Paul, Lardy Neubury, Fijnheer Rob, Sorvillo Nicoletta, ten Brinke Anja, Voorberg Jan CD4+ T cells from patients with acquired thrombotic thrombocytopenic purpura recognize CUB2 domain-derived peptides Blood 2016;127 (12):1606-1609 [PubMed]
  • Verbij Fabian C., Stokhuijzen Eva, Kaijen Paul H. P., van Alphen Floris, Meijer Alexander B., Voorberg Jan Identification of glycans on plasma-derived ADAMTS13 Blood 2016;128 (21):e51-e58 [PubMed]
All Publications
Research programmes

Prof. PhD J.J. Voorberg (Cellulaire Hemostase)

My research programme focuses on cellular aspects of blood coagulation. Special emphasis is directed towards specialzied organelles in endothelial cells. These roganelles, designated Weibel-Palade bodies contain a range of bioactive components invovled in many different processes, such as hemostasis, inflammation, but also angiogenesis and wound healing. Weibel-Palade bodies contain tubular strucutres that are formed by assembly of von Willebrand factor multimers into helical structures. Folowing exocytosis of Weibel-Palade bodies vVWF tubules are rapidly converted into large string-like structures that remain bound to endothelial cells. These so-called VWF strings provide a binding site for blood platelets at sites of vascular injury. The formation of VWF strings is tightly regulated; following its formation VWF strings are rapidly cleaved by ADAMTS13 a metalloprotease that cleaves in the A2 domain of VWF. Functional absence of ADAMTS13 has been linked to the hematological disorder thrombotic thrombocytopenic purpura (TTP). The majority of patients with TTP circulating antibodies directed towards ADAMTS13 have been identified. These antibodies have been shown to target a speciifc site in the spacer domain which precludes its binding to VWF. Currently, we are addressing why antibodies directed towards ADAMTS13 develop in previously healthy individuals. In parallel we also studying the developemnt of inhibitory antibodies in patients with hemophilia A. These so-called FVIII inhibitors provide a major complication in treatment of patients with this X-linked bleeding disorder.

Postdocs
PhD R. Bierings
PhD I. Peyron

PhD Students
M. Swinkels

Others
BEng M. Hofman
BEng P. Kaijen