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Untangling fibroblast plasticity in vascular ageing

Project description

The role of fibroblasts in vascular function and ageing

Ageing cells progressively lose their structural properties and physiological function. With respect to the vascular system, changes in the vascular wall due to ageing could translate into loss of arterial elasticity and reduced compliance. In turn, this increases the risk for hypertension as well as atherosclerotic and cardiovascular disease. The EU-funded FIB-AGE project focuses on the role of fibroblasts in vascular function and ageing. The project will employ a multi-disciplinary approach to characterise different mesenchymal cell populations at the single-cell level. Identification of key molecular players promoting vascular ageing and dysfunction will lead to novel therapeutic targets and interventions.

Objective

Vascular ageing is a major cause of cardiovascular disease, but effective treatment for fibrotic effects of vascular ageing is lacking. Recent studies show that fibroblasts exhibit physiological and pathological functions beyond their central role in fibrosis. Supporting this view of the field, the host lab recently showed great intra-vascular fibroblast plasticity in atherosclerotic and ageing murine arteries. We hypothesize that vascular dysfunction and fibrosis with ageing originate from altered fibroblast plasticity and function.
As part of my career restart, I will join an excellent laboratory, globally recognized for its expertise in advanced vascular biology research, embedded in a modern research institute, equipped with outstanding training facilities. I will combine my acquired scientific, technical and management skills with the infrastructure and expertise of the host lab to comprehensively study ageing-related fibroblast plasticity and to reveal the function of distinct fibroblast subsets in vascular function and ageing. I will combine the hosts cutting-edge high throughput techniques, including single cell sequencing and a newly established fibroblast functionality screening platform (FIBROSCREEN), with my expertise in vascular contractility assessment. I will study fibroblast function and plasticity in vivo, in vitro and in interventional studies ex vivo, in so far unimaginable detail. By sophisticated integration of this obtained data, I will identify key fibroblast players promoting vascular ageing and dysfunction.
With this strategy, I will be the first to reveal subsets of fibroblasts in vascular ageing, to couple their function to vascular ageing progression and to suggest first interventional targets for future exploitation. Together with career guidance by the host, concomitant training opportunities, and a clear plan for dissemination this will ensure my integration into European academia as an independent researcher.

Coordinator

UNIVERSITEIT MAASTRICHT
Net EU contribution
€ 187 572,48
Address
MINDERBROEDERSBERG 4
6200 MD Maastricht
Netherlands

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Region
Zuid-Nederland Limburg (NL) Zuid-Limburg
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 187 572,48