Von Willebrand factor (VWF) is a blood coagulation protein that is produced by endothelial cells in the blood vessel wall. VWF is stored in secretory organelles, so-called Weibel-Palade bodies, from which it is rapidly secreted into the circulation following injury. Low circulating levels of the hemostatic protein Von Willebrand factor (VWF), such as in Von Willebrand disease, give rise to an increased risk of bleeding. The exact mechanisms that give rise to low VWF levels are still unknown but can depend on regulators of membrane trafficking and secretion in endothelial cells, such as SNARE proteins.
In this project, which builds on recent publications from our lab on Weibel-Palade body biogenesis and VWF secretion (Karampini et al., Haematologica 2021, 106(4):1138-1147) and which is funded by the Landsteiner Stichting voor Bloedtranfusie Research (LSBR), we aim to understand how components of the membrane fusion machinery in anterograde and retrograde ER-Golgi transport control VWF trafficking through the endothelial secretory pathway. You will use cutting-edge molecular and cellular analysis, such as high resolution imaging, proteomics and CRISPR gene editing, to unravel the molecular mechanisms that determine Weibel-Palade body biogenesis and VWF secretion.
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