Chronic Thrombo-embolic Pulmonary Hypertension
(CTEPH) is a progressive lung disease, characterized by progressive thrombotic occlusion of the pulmonary vasculature. Recent studies have stressed the importance of inflammation and endothelial injury in the development and progression of CTEPH. In addition, inflammation driven thrombosis in the pulmonary vasculature is also seen in other diseases including Acute Respiratory Distress Syndrome (ARDS) and COVID. The endothelium plays a major role in the control of thrombosis, however, it remains largely unknown how activation or injury of the pulmonary endothelium contributes to CTEPH and other forms of inflammatory thrombosis. This project focuses on the occurrence of in situ thrombosis in the lung circulation, with a specific focus on the contribution of the endothelium to local thrombosis. Elucidating the molecular endothelial mechanisms of in situ thrombosis, the aim is to develop pharmacological strategies to prevent pulmonary thrombosis.
The Amsterdam UMC is a central referral center for CTEPH patients. As patients undergo surgery for CTEPH at a regular basis, our lab has an established pipeline for isolating cells from surgical restmaterial. Following the transcriptomic and proteomic analysis of CTEPH endothelial cells in in last years, we have identified a number of candidate genes/proteins which contribute to in situ thrombosis in CTEPH.
publication link to get an impression of the work.
For the current PostDoc position, we are looking for an enthusiastic PostDoctoal Fellow with biomedical or medical background who is eager to decipher the early steps in the pathophysiology of CTEPH. The work will mainly involve laboratory work using endothelial cells. The Department of Pulmonary Disease hosts a large preclinical laboratory, which directly links fundamental cell biology to daily patient care. Your core business
- Isolation and culture of endothelial cells from patient tissue;
- Endothelial cell culture, using 3D flow models;
- Genetic editing with CRISPR/Cas9, short hairpin RNA and or lentiviral overexpression models;
- Perform Chromatic Immunoprecipitation (ChIP);
- qPCR, Western Blot and immunofluorescence;
- Data analysis;
- Scientific writing.