MSc Lynn Willems

Research:

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of pulmonary embolism (PE),  

characterized by fibro-thrombotic material obliterating large pulmonary arteries and remodelling of precapillary pulmonary arteries. If left untreated, it in progressive right ventricular failure and death. There is consequently an urgent need to i) understand why patients develop CTEPH after acute PE and ii) identify and treat patients at risk of post-surgery persistent pulmonary hypertension.

Peptidyl-Prolyl Cis/Trans Isomerase NIMA-Interacting protein 1 (Pin1) is an enzyme that catalyzes cis-trans isomerization of proline residues, resulting in significant changes in target protein conformation and stability. Recently, Pin1 was shown to enhance Tissue Factor expression in human vascular endothelial and smooth muscle cells; in addition, preliminary results have demonstrated that circulating levels of Pin1 are elevated in CTEPH patients. We consequently hypothesized that Pin1 could serve as a biomarker for early detection of CTEPH and that its inhibition might be beneficial for the prevention of vascular thrombotic diseases such as CTEPH.

Therefore, my PhD project will focus on elaborating the role of Pin1 in the initiation and/or progression of CTEPH. Hence, the aims of the proposal are to investigate, using patient cells, tissue, and preclinical animal models whether i) Pin1 is a discriminating biomarker to identify individuals at risk and ii) Pin1 inhibition restores EC dysfunction, and reduce thrombosis in CTEPH.

Curriculum vitae:

After obtaining my Bachelor’s degree in Biomedical Laboratory Science at Erasmus University College Brussels, I attended the KULeuven University for a Master’s degree in Biochemical Engineering Technology at KULeuven. I performed my master’s thesis within the Cardiovascular departement at the KULeuven on the role of SMAD1/5 signaling in dermal and diaphragmatic lymphatics, which sparked my interest in the circulatory systems. Hence, I started a joint-PhD between KULeuven and Leiden University, which is focused on role of Pin1 on endothelial dysfunction and thrombosis in chronic thromboembolic pulmonary hypertension.