Summary
Despite advances in clinical care, heart failure consequent to myocardial infarction remains a leading cause of mortality worldwide. Absence of cardiac regeneration post-infarction is mostly explained by the reduced mitotic potential of adult cardiomyocytes, that, in comparison with their embryonic counterparts, have an accumulation of morphological, metabolic and biochemical adaptations that render them recalcitrant to proliferation. Devising tools to precisely control the maturational status of cardiomyocytes would enable novel therapies for cardiac regeneration, either by stimulating cell cycle reentry of pre-existing cardiomyocytes, or enhancing the maturational status of cardiomyocytes derived from induced pluripotent stem cells for cell therapy. Novel.CaRe will explore the therapeutic potential of micropeptides, a novel class of proteins that, despite their small size, can play major cellular roles. Based on extensive preliminary work, I propose an ambitious interdisciplinary research program bridging advanced omics, animal models, human samples, bioinformatics, cellular phenotyping and innovative strategies for gene therapy. We will apply new translatomics and proteomics approaches to identify micropeptides conserved across species and modulated during cardiomyocyte maturation, define their cellular functions and test their potential to induce proliferation of cell cycle withdrawn cardiomyocytes or enhance maturation of stem cell-derived cardiomyocytes. In a high-risk, high-gain part of the project, we will develop a novel approach for gene therapy enabling time-controlled, cardiomyocyte-specific expression of a combination of micropeptides normally expressed by embryonic cardiomyocytes and assess if this strategy successfully promotes regeneration of the adult heart post-injury. In conclusion, Novel.CaRe will generate new resources, technology and knowledge, pushing beyond the state-of-the-art in the fields of molecular cardiology and cardiac regeneration.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101115959 |
| Start date: | 01-07-2024 |
| End date: | 31-10-2029 |
| Total budget - Public funding: | 1 592 281,00 Euro - 1 592 281,00 Euro |
Cordis data
Original description
Despite advances in clinical care, heart failure consequent to myocardial infarction remains a leading cause of mortality worldwide. Absence of cardiac regeneration post-infarction is mostly explained by the reduced mitotic potential of adult cardiomyocytes, that, in comparison with their embryonic counterparts, have an accumulation of morphological, metabolic and biochemical adaptations that render them recalcitrant to proliferation. Devising tools to precisely control the maturational status of cardiomyocytes would enable novel therapies for cardiac regeneration, either by stimulating cell cycle reentry of pre-existing cardiomyocytes, or enhancing the maturational status of cardiomyocytes derived from induced pluripotent stem cells for cell therapy. Novel.CaRe will explore the therapeutic potential of micropeptides, a novel class of proteins that, despite their small size, can play major cellular roles. Based on extensive preliminary work, I propose an ambitious interdisciplinary research program bridging advanced omics, animal models, human samples, bioinformatics, cellular phenotyping and innovative strategies for gene therapy. We will apply new translatomics and proteomics approaches to identify micropeptides conserved across species and modulated during cardiomyocyte maturation, define their cellular functions and test their potential to induce proliferation of cell cycle withdrawn cardiomyocytes or enhance maturation of stem cell-derived cardiomyocytes. In a high-risk, high-gain part of the project, we will develop a novel approach for gene therapy enabling time-controlled, cardiomyocyte-specific expression of a combination of micropeptides normally expressed by embryonic cardiomyocytes and assess if this strategy successfully promotes regeneration of the adult heart post-injury. In conclusion, Novel.CaRe will generate new resources, technology and knowledge, pushing beyond the state-of-the-art in the fields of molecular cardiology and cardiac regeneration.Status
SIGNEDCall topic
ERC-2023-STGUpdate Date
12-03-2024
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