- Study of biomarkers for soft tissue mineralization, using pseudoxanhoma elasticum as a model.
- Mineralization of soft tissues, such as skin or blood vessels, leads to destruction of the affected tissue and hence important morbidity and mortality.
- It is a feature in common disorders such as chronic kidney disease, atherosclerosis and diabetes mellitus.
- A more extreme presentation of soft tissue mineralization can be seen in genetic disorders, among which pseudoxanthoma elasticum (PXE) is considered a hallmark disease.
- PXE is an autosomal recessive connective tissue disorder mainly characterized by calcification and fragmentation of the elastic fibers in the extracellular matrix of the skin, eyes and cardiovascular system.
- This results in progressive skin lesions, retinal bleeding leading to blindness and accelerated atherosclerosis with a high cardiovascular risk.
- It is part of a larger spectrum of ectopic mineralization disorders including diseases such as Generalized Arterial Calcification of Infancy (GACI) and the PXE-like syndrome with coagulation factor deficiency. Recent progress in the understanding of the mechanisms leading to calcification in these diseases lead to the identification of two compounds, 4-phenyl butyrate and bisphosphonates, for their treatment.
- Experiments in animal models showed successful results with both compounds on the mineralization process.
- An important caveat is however the lack of reliable non-invasive biomarkers to monitor such treatments when performing a human clinical trial.
- The current project aims to identify and validate biomarkers for soft tissue calcification in general and PXE and its related disorders specifically.
- Several approaches have been described and the added value of combining different biomarkers was demonstrated for other diseases.
- Therefore, we search for biomarkers using three approaches: RNA profiling - looking for coding and non-coding RNA signatures; DNA methylation analysis - looking for epigenetic biomarkers; and high-definition mass spectrometry - looking at disease-specific differences in profiles of proteins.
- This is done on patients, cell cultures and animal models (zebrafish models) of PXE and its related diseases GACI and PXE-like disease with coagulation deficiency.
Profile of the candidate
- You hold or plan to hold a Master of Science Degree in Medicine, Pharmaceutical Sciences, Bio-engineer, Biochemistry and biotechnology, Biomedical sciences or similar. You have a strong interest in research and are highly motivated to complete a PhD. Commitment and perseverance are necessary.
- You are willing to work in an interactive research team.
- You have good didactic and communicative skills. Good academical skills and grades and profound knowledge of English and Dutch are mandatory.
- Candidates must be in possession of a certificate “working with laboratory animals” or be prepared to obtain this certificate.