# Genetic dissection of Cardiac Conduction System homeostasis and Repair

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2024 · $641,791

## Abstract

ABSTRACT
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. Despite its
importance, the molecular mechanisms underlying CCS homeostasis and regeneration are poorly understood.
Hippo signaling, a fundamental molecular signaling pathway, inhibits cardiomyocyte proliferation and
regeneration. However, the role of Hippo signaling in the CCS is largely unclear. We made the first evidence of
an essential role for the Hippo signaling in maintaining CCS homeostasis and repair after injury, which functions
via the canonical Hippo signaling mediated by Hippo downstream effectors Yap and Taz. Deletion of Hippo
signaling Lats1 and Lats2 in the CCS caused disrupted CCS homeostasis and cardiac arrhythmias in adult mice,
which is rescued via genetic deletion of Yap/Taz in the CCS. However, upon CCS injury, Lats1/2 deletion is
protective and improved cardiac function. Our preliminary data also suggested a crosstalk between the Hippo
and TGF-β signals, as well as Yap/Taz interactions with different transcription factors in no-injury and injury CCS.
Here we will further study these findings at the single-cell level to provide unprecedented and novel mechanistic
insight(s) into the molecular regulatory mechanisms of the CCS. We are aimed to identify therapeutic targets
applicable to the future treatment of human patients with CCS dysfunction and regenerative medicine.

## Key facts

- **NIH application ID:** 10803751
- **Project number:** 2R01HL142704-04A1
- **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:** 2024
- **Award amount:** $641,791
- **Award type:** 2
- **Project period:** 2018-09-25 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803751

## Citation

> US National Institutes of Health, RePORTER application 10803751, Genetic dissection of Cardiac Conduction System homeostasis and Repair (2R01HL142704-04A1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10803751. Licensed CC0.

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