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CardHeal SIGNED

Novel strategies for mammalian cardiac repair

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EC-Contrib. €

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Project "CardHeal" data sheet

The following table provides information about the project.

Coordinator
WEIZMANN INSTITUTE OF SCIENCE 

Organization address
address: HERZL STREET 234
city: REHOVOT
postcode: 7610001
website: www.weizmann.ac.il

contact info
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surname: n.a.
function: n.a.
email: n.a.
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 Coordinator Country Israel [IL]
 Total cost 2˙268˙750 €
 EC max contribution 2˙268˙750 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2018
 Duration (year-month-day) from 2018-06-01   to  2023-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    WEIZMANN INSTITUTE OF SCIENCE IL (REHOVOT) coordinator 2˙268˙750.00

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 Project objective

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.

 Publications

year authors and title journal last update
List of publications.
2019 Rachel Sarig, Rachel Rimmer, Elad Bassat, Lingling Zhang, Kfir Baruch Umansky, Daria Lendengolts, Gal Perlmoter, Karina Yaniv, Eldad Tzahor
Transient p53-Mediated Regenerative Senescence in the Injured Heart
published pages: 2491-2494, ISSN: 0009-7322, DOI: 10.1161/circulationaha.119.040125
Circulation 139/21 2020-01-30
2019 Oren Yifa, Karen Weisinger, Elad Bassat, Hanjun Li, David Kain, Haim Barr, Noga Kozer, Alexander Genzelinakh, Dana Rajchman, Tamar Eigler, Kfir Baruch Umansky, Daria Lendengolts, Ori Brener, Nenad Bursac, Eldad Tzahor
The small molecule Chicago Sky Blue promotes heart repair following myocardial infarction in mice
published pages: , ISSN: 2379-3708, DOI: 10.1172/jci.insight.128025
JCI Insight 4/22 2020-01-30

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