# Cardiac Lineage-Specific Molecular Mechanisms of Heart Failure

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $766,287

## Abstract

Project Summary
The heart consists of a multitude of diverse cardiac cell types, including but not limited to cardiomyocytes,
cardiac fibroblasts, epicardial cells, endothelial/endocardial cells and smooth muscle cells, which coordinate to
sustain cardiac function and circulation throughout the body. Thus, regulated maintenance of these cell types
is crucial for optimal heart performance and disrupting the function of specific cell lineages can result in distinct
heart diseases including heart failure, which is a major leading cause of morbidity and mortality
worldwide. However, what are the specific cell lineages affected during heart failure and how do gene
regulatory networks control genetic programs that direct their pathologic outcomes are key biomedical
questions that remain to be resolved. To address these issues, we have created an interdisciplinary team that
includes physician-scientists who will collect patient heart tissue samples to investigate molecular mechanisms
involved in the pathogenesis of heart failure; genomic and epigenomic experts who will employ cutting-edge
single-cell sequencing and chromatin analysis technologies to examine cell-type specific chromatin
accessibility-interactions and corresponding gene expression; and stem cell biologists who will utilize human
pluripotent stem cell cardiac models and state-of-the-art genome-editing strategies to perform functional
confirmation studies. Through these integrative efforts and analyses, we plan to examine the hypothesis that
cis-regulatory elements and their enhancer-promoter interactions dynamically function and coordinate in a cell-
type specific manner to direct lineage-specific gene expression during cardiac tissue homeostasis, and altering
these highly-regulated cell-type specific cis-regulatory elements and corresponding gene regulatory networks
can lead to heart failure. Specifically, we propose to 1) identify cis-regulatory elements and cell-types that are
affected by heart failure-associated non-coding genetic variants; 2) investigate how gene regulatory networks
controlling specific cardiovascular cell-types are altered during heart failure; and 3) examine how perturbations
of cell-type specific cis-regulatory elements and gene regulatory networks during heart failure impact cell
function and gene expression.

## Key facts

- **NIH application ID:** 10558570
- **Project number:** 5R01HL156576-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Neil C Chi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $766,287
- **Award type:** 5
- **Project period:** 2021-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10558570

## Citation

> US National Institutes of Health, RePORTER application 10558570, Cardiac Lineage-Specific Molecular Mechanisms of Heart Failure (5R01HL156576-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10558570. Licensed CC0.

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