Project description
Engineered heart tissue approach to study mechanisms of heart failure
The ERC-funded DISSECT-HF project aims to create engineered heart tissue (EHT) with the use of human induced pluripotent stem cells (hiPSC) obtained from patients with specific forms of heart failure (HF). The project will focus on three HF aetiologies with a clear trigger and a large inter-individual susceptibility that include pregnancy-induced HF, anthracycline cardiotoxicity, and phospholamban cardiomyopathy. The goal is to elucidate common pathophysiological mechanisms involved in the development of HF. A deep understanding of HF molecular mechanisms and knowledge about inter-individual susceptibility will greatly advance treatment possibilities.
Objective
The objective of DISSECT-HF is to generate engineered heart tissue (EHT) with the use of human induced pluripotent stem cells (hiPSC) from specific forms of heart failure (HF). It focusses on three etiologies of HF with a clear trigger and a large inter-individual susceptibility (pregnancy induced HF, anthracycline cardiotoxicity and PLN cardiomyopathy) to unravel common pathophysiological mechanisms involved in the development of HF. The rationale is: - Better understanding of molecular pathways leading to HF and knowledge about inter-individual susceptibility is needed to improve treatment. - For detection of changes on a molecular level cardiac tissue is needed. - Using innovative experimental approaches, such as dynamic loaded EHT (dyn-EHT), patient specific cells, unbiased target finding and deep phenotyping, I will dissect common disease pathways in the development of HF. SPECIFIC OBJECTIVES: 1. Construction of dyn-EHT from patient specific hiPSC derived cardiomyocytes, endothelial cells and fibroblasts. 2. Generation and deep-phenotyping of dyn-EHT from: A) Females with pregnancy induced HF (susceptible) and siblings with a normal pregnancy (resilience) B) Cancer patients with severe HF after anthracyclines (susceptibility) and patients who could resist high dose anthracyclines (resilience) C) Patients with an early PLN cardiomyopathy phenotype (susceptible) versus elderly asymptomatic PLN mutation carriers (resilience) 3. Identify overlapping and diverse factors. 4. Validate discoveries and apply in unique human cohorts with data on incident HF. WORKPACKAGES: WP1: Optimize construction of dyn-EHT from patient specific hiPSC. WP2: Phenotyping of dyn-EHT from the three HF etiologies focussing on susceptibility and resilience. WP3: Explore the transcriptome and proteome and apply a systems biology approach. WP4: Validate results and explore human relevance in a large cohort with unique phenotyping.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences genetics RNA transcriptomes
- natural sciences biological sciences genetics mutation
- medical and health sciences clinical medicine obstetrics
- medical and health sciences clinical medicine oncology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2021-COG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
9713 GZ Groningen
Netherlands
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