# Cellular and Molecular Mechanisms of Atrial Cardiomyocyte Lineage Commitment

> **NIH NIH R00** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $249,998

## Abstract

Project Summary
The purpose of this five-year proposal is to provide an integrative and personalized training program for the
applicant to transition into an independent academic position as a basic scientist in cardiac development and
regeneration. The long-term goal is to understand the underlying mechanisms of atrial CM lineage development
and atria-related congenitial heart diseases. The applicant has a strong background in single-cell gene
expression analysis, tissue cell culture, and mouse embryonic development with facility at the bench in all
aspects of single-cell analysis, tissue cell culture, and mouse embryos dissection. This career development plan
(K99 phase) will provide additional training in embryonic histology analysis, ChIP-seq data analysis, and cardiac
phenotypic analysis of transgenic mouse embryos to investigate the mechanisms of RA signaling in promoting
atrial CM lineage development. The applicant will also receive a wealth of informal and didactic training at
Stanford University in specialized areas such as professional development and writing skills, which will be critical
for the applicant to gain autonomy and launch a productive career as an independent investigator. Under the
expert mentorship of Dr. Sean Wu, MD PhD along with the assembled advisory committee (Dr. Quertermous,
Dr. Ruiz-Lozano, Dr. Krasnow, Dr. Bernstein, and Dr. Martin), the applicant will receive the necessary guidance
and resources to accomplish these goals and efficiently transition to independence during the R00 phase.
Atrial CM lineage development is a basic cellular process, and retinoic acid (RA) signaling has been reported to
be a critical pathway in promoting this process, but the underlying cellular and molecular mechanisms are still
largely unclear. The applicant has developed a single cell progeny assay to analyze the lineage specification of
cardiac progenitor cells, and identified a list of highly promising atrial CM specific genes with single cell RNA
sequencing. In this proposal, he will use conditional knockout mice, single-cell progeny assay, RA signaling
report assay, gene overexpression or downregulation assay, and ChIP-seq technology to analyze the cellular
and molecular mechanisms of RA signaling in promoting atrial CM lineage development. Results from this
research are expected to provide insights into the mechanisms of atrial tissue-related congenital heart diseases.
His specific aims are: Aim 1 (K99): To define the cellular mechanisms of RA signaling in promoting atrial CM
lineage development. Aim 2 (R00): To define the molecular mechanisms of RA signaling in promoting atrial CM
lineage development.

## Key facts

- **NIH application ID:** 10138515
- **Project number:** 5R00HL133472-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Guang Li
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,998
- **Award type:** 5
- **Project period:** 2019-04-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10138515

## Citation

> US National Institutes of Health, RePORTER application 10138515, Cellular and Molecular Mechanisms of Atrial Cardiomyocyte Lineage Commitment (5R00HL133472-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10138515. Licensed CC0.

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