# Defining the Unique Role of Fibroblasts in Neonatal Cardiac Regeneration

> **NIH NIH F30** · UNIVERSITY OF ROCHESTER · 2021 · $51,036

## Abstract

Project Summary
 Adult hearts lack the capacity to regenerate. Since mature (adult) cardiomyocytes (CMs; cardiac muscle
cells) are post-mitotic, the fibrotic scar formed by cardiac fibroblasts (CFs) after a myocardial infarction is
irreversible. This scar often contributes to left ventricular dysfunction and heart failure, the leading causes of
death in US. Recent studies have found that the mammalian neonatal heart has a remarkable capacity to resolve
fibrosis and regenerate after an injury. This unique phenomenon may be mediated, in part, by CFs through
intrinsic intracellular factors or via extrinsic signals in the neonatal cardiac extracellular matrix. Evaluation of
published RNA-sequencing data has revealed an enrichment of Amphiregulin (i.e. Areg) in the heart during the
neonatal regenerative window. Areg is a pro-regenerative cytokine that has been also shown to stimulate CF
proliferation and fibrosis in the adult heart. However, the cellular responses to Areg may be different in the highly
regenerative neonatal heart. In this study, we will evaluate the contributions of neonatal CFs to cardiac repair
(Aim 1) through selective cell depletion and RNA sequencing while simultaneously defining their response to
pro-regenerative cytokines such as Areg (Aim 2) through in vivo and in vitro studies. Establishing the unique role
of CFs during neonatal cardiac regeneration will lead to more targeted approaches to combat the irreversible
cardiac fibrosis present after adult cardiac injury. This proposal also details a training plan of clinical activities to
complement the proposed research plan of the applicant. The longitudinal clinical electives in cardiovascular and
regenerative medicine will provide a better understanding of the clinical context of the research. Under the
guidance of the sponsor, thesis committee, and advisory committee, the applicant will develop her knowledge in
experimental design, scientific communications, and techniques in cardiovascular research. This proposal
contributes to current knowledge in cardiac fibrosis while training the applicant to be a clinician-scientist.

## Key facts

- **NIH application ID:** 10328485
- **Project number:** 5F30HL150883-02
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Adwiteeya Misra
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $51,036
- **Award type:** 5
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328485

## Citation

> US National Institutes of Health, RePORTER application 10328485, Defining the Unique Role of Fibroblasts in Neonatal Cardiac Regeneration (5F30HL150883-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10328485. Licensed CC0.

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