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Posted on : 23 May 2017
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 candidateYou 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.How to applyInterested candidates should send their application (including motivation letter, CV and potential referees) to Prof. Dr. Olivier Vanakker, Center for Medical Genetics, Ghent University Hospital, Building K5, De Pintelaan 185, 9000 Gent or Olivier.Vanakker@Ugent.be. The vacancy remains open until a suitable candidate is found. A first evaluation of the received applications will be done on August 1st 2017.
9000 Ghent Belgium
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