The endothelium is a central mediator of cystic fibrosis lung disease

As PhD candidate I will work under the co-supervision of Prof. Peter Carmeliet (Laboratory of Angiogenesis and Vascular Metabolism, VIB-KU Leuven CCB) and Prof. Peter Witters (clinician at UZ Leuven and specialist in CFLD). Prof Witters showed the involvement of endothelial cells (ECs) in cystic fibrosis (CF) pathology where they act as a semipermeable barrier, a key regulator of angiogenesis, coagulation, the vascular tone and inflammatory responses. It could contribute to different aspects of the disease including cardiovascular symptoms, excessive blood vessel formation, pulmonary and portal hypertension and CF-related diabetes. Despite the important role of vascular endothelium in many biological processes, it has largely been under investigated in CF. In this exciting project I will analyse single cell RNA sequencing data in explant lungs of CF patients. This will allow studying the specific contribution of ECs to the pathogenesis of CF lung disease. Validation of the findings will be performed by using immunohistochemistry, in situ hybridisation and biochemistry assays on collected lung tissue. Elucidating the pathophysiology will allow for the discovery of biomarker for endothelial disease in CF (e.g. microvesicles) and would lead to new therapeutic options which will be tested in vitro using cellular models (HUVEC, BOEC) and in vivo using murine models. Altogether this project will increase our understanding in the pathophysiology, define relevant biomarkers and could lead to novel therapies.