# Genetic dissection of Cardiac Conduction System homeostasis and regeneration

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $354,994

## Abstract

Abstract
Genetic dissection of Cardiac Conduction System homeostasis and regeneration
 The cardiac conduction system (CCS) is required for initiating and maintaining regular rhythmic heartbeats.
CCS defects commonly give rise to arrhythmia, a leading cause of morbidity and death worldwide. CCS
dysfunction can be inherited or acquired due to conditions such as drug toxicity or myocardial infarction. It is
imperative to elucidate the molecular mechanisms underlying CCS homeostasis to facilitate development of
cardiac therapies. Importantly, these mechanisms are poorly understood owing to numerous technical
challenges. Hippo signaling, a pivotal organ size control pathway, inhibits cardiomyocyte proliferation and
regeneration. However, the role of Hippo signaling in the CCS is unclear. Here we will determine whether Hippo
signaling regulates CCS homeostasis. Additionally, we will identify regulators and targets of Hippo signaling in
the CCS. Our preliminary observations revealed that disruption of Hippo signaling in the CCS caused cardiac
arrhythmias in mice, suggesting an important role of Hippo signaling in CCS homeostasis. Notably, deletion of
Hippo signaling rescued cardiac rhythm and function after CCS cell ablation, suggesting that repression of Hippo
signaling protects the CCS from damage. In addition, we identified candidate microRNA regulators and
downstream targets of Hippo signaling. Here we propose to investigate the function and molecular regulatory
mechanism of Hippo signaling in the CCS through in the following specific aims: 1) To define Hippo signaling
function in CCS homeostasis and elucidate the mechanism by which repression of Hippo signaling protects the
CCS from damage, 2) Identify upstream microRNA regulators of Hippo signaling in the CCS, and 3) Identify
downstream targets of the Hippo pathway that modulate CCS function.

## Key facts

- **NIH application ID:** 10084306
- **Project number:** 5R01HL142704-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Jun Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $354,994
- **Award type:** 5
- **Project period:** 2020-01-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10084306

## Citation

> US National Institutes of Health, RePORTER application 10084306, Genetic dissection of Cardiac Conduction System homeostasis and regeneration (5R01HL142704-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10084306. Licensed CC0.

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