Bart van Vlijmen

The primary objective my research line is to dissect the biological mechanism(s) underlying acquired and genetic risk factors for thrombosis. Using recombinant in vivo models that express disease phenotypes (obesity, spontaneous thrombosis) or that lack genes key to the mechanistic pathways of interest, we have studied several risk conditions in relation to coagulation and thrombosis. Relevant technologies were successfully introduced including analysis of hepatic and vascular coagulation gene expression, mass-spectrometry-based targeted (plasma) proteomics, experimental and spontaneous thrombosis models, and an in vivo RNA interference (RNAi) strategy that allows simple and fast knockdown of hepatically expressed genes. Currently, we are succesfully using this technology to study a number of hepatic genes (potentially) relevant coagulation and thrombosis. RNAi studies on protein C and antithrombin proved very successful in unravelling the in vivo function of these anticoagulants and also provided novel, controlled models for both venous (Safdar et al. Blood 2013; Heestermans et al. Blood 2019) and arterial thrombosis research (Ouweneel et ATVB 2017). Our latest RNAi and recombinant mouse studies focus on SLC44A2, a novel venous thrombosis susceptibility gene, identified by our group in a meta-analysis of genome wide association studies (Germain et al. 2015). The research on SLC44A2 is sponsored by the Dutch Thrombosis Foundation and includes collaborations with the University of Michigan, Ann Arbor, USA and Marseille, France. As SLC44A2 also plays a role in transfusion-related disease (TRALI), the link between TRALI and VTE, i.e. two seemingly urelated diseases, is also investigated in collaboration with the Department of Clinical Immunology and Transfusion Medicine, Giessen University (Germany) under sponsorship of the Landsteiner Foundation for Blood Transfusion Research (LSBR).