Community Research and Development Information Service - CORDIS

Periodic Report Summary 1 - STRESSFATE (To Notch up a broken heart)

Heart failure is a major health issue and a cause of death and disability. The endogenous regenerative capacity of the heart is too weak to recover from damage and instead the heart repairs damage by synthesis of a scar tissue leading to functional deterioration. To improve cardiac regeneration, stem cell therapies and material-based approaches have been developed but up till now with limited success as we still lack detailed knowledge of and the functional technology to guide the regenerative process. Cardiac tissue is composed of muscle cells, non-muscle cells and extracellular matrix organized into a complex 3-dimensional architecture. The regeneration process requires specialization of cardiac stem cells in combination with remodelling of the extracellular matrix to form a functional contractile tissue. The Notch signaling pathway is a unique therapeutic target for regeneration of the heart, but we no nothing about the crosstalk between Notch and the biomechanical microenvironment. We aim to develop an in vitro model system using in situ differentiation of cardiac stem cells on 3-dimensional microtissue. The tissue can be engineered to mimic healthy or diseased myocardium tissue and be mechanically stimulated to mimic the beating heart. Using the model we aim to gain in-depth understanding on how the extracellular matrix and changes therein and the Notch signalling pathway, are interlinked. To use Notch modulation as a handle in cardiac regeneration we will develop technology for temporally and spatially controlled modulation of Notch signalling and build a prototype of functional scaffold for cardiac stem cell differentiation comprised of controlled delivery of Notch modulators from a synthetic matrix.

The candidate, a cell biologist, transferred to Eindhoven University of Technology (TU/e) as an assistant professor 2013 to build up a research line focusing on mechanobiology in cardiovascular tissues and especially on the integration of the mechanical environment with cell signaling through the Notch pathway. She aims to use the mechanistic insight to develop smart biomaterials for cardiovascular therapies and regeneration. She has developed a number of model systems (vessels on Chips, mechanically active microtissues ect) to address her research questions and is currently collaborating with biomaterials scientist on the design of biofunctionalized scaffolds to steer Notch activity for in situ regeneration of heart valves, cardiac stem cell therapy and tissue vascularization.

She has published more than 15 research papers and has several under review on Notch signaling and materials to steer Notch signaling as a corresponding author since 2014. She has initiated collaboration with scientist working on numerical models and is finalizing the first paper on the description of an computational model integrating Notch signaling with the hemodynamic environment in vascular morphogenesis.

She obtained a permanent position by January 2014 and is currently under evaluation for promotion to associate professor.

She has been engaged in several out reach activities (media appearances, news paper interviews etc) and has been invited to several international conferences (Gordon Conferences, The Notch meeting etc).

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Life Sciences
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