# Regulatory Mechanisms of Myocardial Reprogramming in Zebrafish

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $387,500

## Abstract

Cardiomyocytes experience a wide range of physiologic and pathologic stimuli, which can influence their
cellular state. Although cardiomyocyte hypertrophy and hyperplasia are well known adaptive cardiac cellular
responses, some cardiomyocytes also retain the capacity to reprogram (i.e. cardiac plasticity) in order to alter
their differentiation state and identity to adapt to stress. For instance, cardiomyocyte de-differentiation is a
component of the maladaptive response during heart failure; a portion of the right ventricle in Ebstein's
anomaly, which is exposed to altered hemodynamic forces, becomes “atrialized”; and both cardiomyocyte de-
differentiation and trans-differentiation regulate cardiac regeneration under certain conditions. Thus, this
cardiac “adaptive cellular reprogramming” can act in not only pathologic but also beneficial circumstances.
However, despite the importance of cardiac reprogramming in regulating adaptive responses to stimuli, our
understanding of the intrinsic processes that control cardiomyocyte plasticity and the external cues that
activate cardiac reprogramming to modify cardiomyocyte differentiation states and cell identities remains yet to
be fully elucidated. Thus, the overall goals of these proposed studies are to illuminate the underlying
mechanisms that 1) control cardiomyocyte plasticity, 2) activate cardiomyocyte reprogramming in plastic
cardiomyocytes and 3) regulate the reprogramming of these cardiomyocytes. The results of these cardiac
reprogramming studies will not only illuminate how cardiomyocytes may adaptively (or maladaptively)
reprogram in response to cellular stress in vivo but also provide further insight into how to direct mammalian
cells from various cell sources (i.e. fibroblasts, pluripotent stem cells, cardiac progenitor cells) into functional
ventricular and atrial cardiomyocytes for human cardiac disease modeling and therapeutic screening in cell
culture systems as well as for human cardiac regenerative therapies.

## Key facts

- **NIH application ID:** 9902536
- **Project number:** 5R01HL132298-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Neil C Chi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,500
- **Award type:** 5
- **Project period:** 2017-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902536

## Citation

> US National Institutes of Health, RePORTER application 9902536, Regulatory Mechanisms of Myocardial Reprogramming in Zebrafish (5R01HL132298-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9902536. Licensed CC0.

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