Dr C Reutelingsperger
Applications accepted all year round
About the Project
EVOluTION – European Vascular Interventions and Therapeutic Innovation Network is a Marie Skłodowska-Curie Actions (MSCA) Innovative Training Network (ITN) offering joint research training at the PhD level.
EVOluTION will train 11 PhD students in the tissue-protective processes operative in our body, with exemplars and proof-of-concept investigations into 1) dietary approaches to augment synthesis and release of vasculo-protective mediators, 2) mechanisms, mediators and targets of the resolution of inflammation arena, and 3) chemical, biochemical and engineering approaches for therapeutic innovation.
Research project
Vascular calcification is an actively regulated process involving vascular smooth muscle cells (VSMC), extracellular vesicles (exosomes) and proteins such as sphingomyelin phosphodiesterase-3 (SMPD3), the vitamin-K dependent Matrix Gla Protein (MGP) and Bone Morphogenetic Proteins (BMP). The objectives are to develop targeted therapeutic strategies that limit exosome formation and that harness MGP to suppress vascular calcification. Research and training activities of ESR 4 will focus on drug discovery and drug testing (High Content Analysis and preclinical evaluation). ESR 4 will combine in silico approaches utilizing structural bioinformatics methods (identification and priorization of druggable pockets in target proteins like SMPD3, BMP-2 and -4) and Structure-Based Virtual Screening of small molecule inhibitors of calcification. In silico analysis will be performed with technology developed in house and in vitro analyses will be performed using VSMC cultures and the BioHybridTM system (calcification and exosome production as readout). Best hit molecules will be tested in vivo in mouse models of vascular calcification: intimal calcification (apoE-/- on Western Type Diet supplemented with i) vitamin K-nutraceuticals, and ii) warfarin); medial calcification (apoE-/- on Western Type Diet supplemented with high phosphate in combination with unilateral nephrectomy).
Expected Results
Functional platform of novel therapeutic small molecules to treat vascular calcification.
Planned secondment(s)
1) NattoPharma, Norway (M24 – 25, 2 months): To study small molecules on vitamin K activity.
2) LMU, Germany (M30 – 31, 2 months): To study small molecules in experimental atherosclerosis.
Main Supervisor
Name: Chris Reutelingsperger
Email: [Email Address Removed]
Website: https://www.carimmaastricht.nl/profile/c.reutelingsperger
Host Institution
CARIM School for Cardiovascular Diseases
Maastricht University
Universiteitssingel 50
6229 ER Maastricht
The Netherlands
For informal enquiries regarding the research project, plesae contact the supervisor. For enquiries related to the application process, please contact Annabelle Scott [Email Address Removed].
Funding Notes
Applicants must satisfy the donor's eligibility requirements: at the time of the recruitment by the host organisations, the candidates 1) must not have resided in the host country for more than 12 months in the last 3 years, and 2) must be in the first four years of his/her research career and not have a doctoral degree.
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