CardHeal
Financiado
Novel strategies for mammalian cardiac repair
Recent ground-breaking studies by my team and others demonstrated that latent heart regeneration machinery can be awakened even in adult mammals. My lab’s main contribution is the identification of two, apparently different, molec...
Recent ground-breaking studies by my team and others demonstrated that latent heart regeneration machinery can be awakened even in adult mammals. My lab’s main contribution is the identification of two, apparently different, molecular mechanisms for augmenting cardiac regeneration in adult mice. The first requires transient activation of ErbB2 signalling in cardiomyocytes and the second involves extra cellular matrix-driven signalling by the proteoglycan agrin. Impressively, both mechanisms promote a major regenerative response that, in turn, enhances cardiac repair. In CardHeal we will use the two powerful regenerative models to obtain a holistic view of cardiac regeneration and repair mechanisms in mammals (mice and pigs).
In Aim 1, we will explore the molecular mechanisms underlying our discovery that transient activation of ErbB2 in adult cardiomyocytes results in massive cardiomyocyte dedifferentiation and proliferation followed by new vessels formation, scar resolution and functional cardiac repair. Specific objectives focus on ErbB2-Yap/Hippo signalling during cardiac regeneration; ErbB2 activation in a chronic heart failure model; ErbB2-induced regenerative EMT-like process; and cardiomyocyte re-differentiation.
In Aim 2, we will investigate the therapeutic effects of agrin, whose administration into injured hearts of mice and pigs elicits a significant regenerative response. Specific objectives are matrix-related cardiac regenerative cues, modulation of the immune response, angiogenesis, matrix remodeling, and developing a preclinical, large animal model to study agrin efficacy for cardiac repair.
Interrogating the differences and similarities between our two regenerative models should give us a detailed roadmap for cardiac regenerative medicine by providing deeper knowledge of the regenerative process in the heart and pointing to novel targets for cardiac repair in human patients.
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Duración del proyecto: 60 meses
Fecha Inicio: 2018-05-17
Fecha Fin: 2023-05-31
Fecha Fin: 2023-05-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2023-05-31
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2017-ADG:
ERC Advanced Grant
Cerrada
hace 7 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
WEIZMANN INSTITUTE OF SCIENCE
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
401.48K€ |
Participante