# Molecular control of cardiac regenerative potential

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $732,709

## Abstract

Project Summary/Abstract
Around birth, mammals undergo the most complex and profound physiologic and metabolic changes for
adaptations to the extrauterine life. Intriguingly, this process is accompanied with loss of tissue regenerative
potential in many organs including the heart, skin and brain. The upstream signals that drive the perinatal loss
of organ regenerative capacity are largely unknown. Our study of heart regeneration suggests that activation of
thermogenic pathways such as the perinatal increase of circulating thyroid hormone levels and adrenergic
receptor activity during the ectotherm-to-endotherm transition inhibits cardiomyocyte proliferative potential and
heart regeneration in ontogeny and phylogeny (Hirose et al., Science 2019; Payumo et al., Circulation 2021).
Following this direction, we recently made preliminary yet intriguing observations that another thermogenic
pathway also regulates mammalian cardiomyocyte renewal potential. In this proposal, we will investigate
whether thermogenic tissues control mammalian cardiomyocyte cell-cycle arrest after birth. Their impact on
cardiomyocyte regeneration and heart repair after myocardial infarction will also be determined in adult mice.
Furthermore, the signaling molecules mediating the thermogenic organ-heart crosstalk will be examined.
Collectively, our proposed experiments will shed lights into the molecule mechanism and fundamental principle
governing the loss of organ regenerative capacity after the acquisition of endothermy.

## Key facts

- **NIH application ID:** 10758214
- **Project number:** 5R01HL138456-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Guo Huang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $732,709
- **Award type:** 5
- **Project period:** 2017-12-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10758214

## Citation

> US National Institutes of Health, RePORTER application 10758214, Molecular control of cardiac regenerative potential (5R01HL138456-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10758214. Licensed CC0.

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