Prof Sander (A. B.) Meijer PhD
Cellular receptors involved in the clearance of factor VIII and factor IX. Replacement therapy for hemophilia patients, which have a functional absence of factor VIII or factor IX, involves frequent intravenous infusions (every 48-72 hours) with either plasma-derived of recombinant factor VIII of factor IX. This high infusion frequency is the consequence of a particularly fast clearance mechanism that removes these haemostatic proteins from the circulation resulting in a half-life that varies between 14 and 18 hours. Insight into this mechanism may provide the basis for future treatment strategies that prolong half-life in vivo. Previous research has addressed the clearance mechanisms of factor VIII from the circulation. This has resulted in the identification of a factor VIII clearance pathway, which involves the low-density lipoprotein receptor-related protein (LRP) and low-density lipoprotein receptor (LDLR). Evidence for the involvement of LRP and LDLR in factor VIII clearance was obtained employing purified receptor/ligand systems, cellular degradation experiments and in vivo studies. Future studies aim at identification of critical residues in these coagulation factors that selectively interact with clearance receptors. This may ultimately result in the design of novel therapeutics that prolong half life of factor VIII and IX in the circulation.
- Protein chemistry (GFP tagged proteins)
- Molecular modeling
|Professor of Pharmaceutical plasma proteins, Faculty of Pharmacy, Utrecht University
|Staff member of Department of Plasma Proteins
|PhD student at the Department of Biomolecular Sciences, Wageningen University