# Forkhead Transcription Factor is required for Cardiomyocyte Proliferation

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $45,520

## Abstract

Project Summary/Abstract
Myocardial infarction results from ischemic injury to the coronary arteries, and triggers localized cardiomyocyte
(CM) death as well as turnover of damaged cardiac tissue into fibrotic tissue. Adult mammalian CMs fail to
sufficiently proliferate post-injury and allow for persistent fibrosis within the heart which elevates patient
morbidity. Heart disease remains the leading cause of death in the United States and current therapeutics only
attenuate the progression of heart disease: they cannot reverse cardiac damage by inducing CM proliferation.
However, it may be possible to stimulate adult CM proliferation as mono- and bi-nucleated CMs were recently
shown to proliferate in post-natal, young, mammalian hearts. Therefore, it is imperative to discern the
mechanisms driving CM proliferation and if their manipulation can improve pediatric and adult CM proliferation
and cardiac regeneration. In this proposal, we will utilize a ventricular amputation model in adult zebrafish to
study cardiac regeneration. Adult zebrafish CMs are mono-nucleated, diploid, and display robust proliferation
after injury which makes them ideal to identify and study the molecular mechanisms regulating CM
proliferation. Using transcriptome profiling (RNA-Seq) after ventricular resection, we identified that Forkhead
box M1, Foxm1, expression increased during the early stages of cardiac regeneration. The goals of this
proposal are to determine the role of Foxm1 in cardiac regeneration and CM proliferation. We will utilize loss-
of-function approaches to study foxm1 mutants after cardiac injury. In addition, we will address the question
whether Foxm1 is activated by the Ras/MAPK signaling axis, and investigate downstream foxm1 target genes
via transcriptional profiling. These studies will be critical in understanding how CMs are activated to become
mitotic after injury. Understanding these intricate mechanisms will provide us with new insights to stimulate
cardiomyocyte proliferation and discover genetic targets to enhance cardiac regeneration in mammalian
systems.

## Key facts

- **NIH application ID:** 10023934
- **Project number:** 5F31HL149148-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Daniel Anthony Zuppo
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-08-30 → 2022-08-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023934

## Citation

> US National Institutes of Health, RePORTER application 10023934, Forkhead Transcription Factor is required for Cardiomyocyte Proliferation (5F31HL149148-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10023934. Licensed CC0.

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