# Self organization of the sinoatrial node

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $498,847

## Abstract

Project Summary/Abstract
The sinoatrial node (SA node or SAN) is a minuscule, heterogeneous structure which initiates
and sets the rhythm of the heartbeat. Recent insights into embryonic development have
pinpointed T-box (TBX) transcription factors as key determinants of the SAN differentiation. Tbx18,
in particular, has been shown to be indispensable for the specification of the SA node during
development. In the past decade, we have learnt much about the electrophysiological bases of
pacemaker cell automaticity. The membrane and Ca2+ clock mechanisms can explain the
automaticity at the single, pacemaker cell level. However, heart rhythm cannot arise from mere
summation of the spontaneous electrical activities from single pacemaker cells. Rather, the
intricate architecture of the sinoatrial node allows the <10,000 nodal pacemaker cells to pace-
and-drive the atrial myocardium. However, little is known about how the SAN can self-assemble
its structure and the molecular determinants of synchronous sinus rhythm; i.e., how the
pacemaker cells and the rich network of non-myocytes become confined into the SA node area
to achieve its sole function of pace-and-drive. We hypothesize that Tbx18 induces acute,
inflammatory signals, and the acute inflammatory cytokines facilitate homing and/or proliferation
of non-myocytes such as fibroblasts and macrophages, and thus self-assembly of the developing
SAN. Somatic gene transfer technology, somatic cell reprogramming, and in vitro & in vivo models
of electrophysiology are the main tools of this study. This proposal is deliberately mechanistic,
with the singular goal of understanding the molecular determinants of synchronous sinus rhythm
generation.

## Key facts

- **NIH application ID:** 10052229
- **Project number:** 1R01HL147270-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Hee Cheol Cho
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $498,847
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10052229

## Citation

> US National Institutes of Health, RePORTER application 10052229, Self organization of the sinoatrial node (1R01HL147270-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10052229. Licensed CC0.

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