# Elucidation of the Role for PHF7 in Direct Reprogramming of Fibroblasts to Cardiomyocytes

> **NIH NIH F32** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $42,725

## Abstract

Project Summary
Ischemic heart disease is the leading cause of morbidity, mortality, and healthcare expenditure worldwide due
to an inability of the heart to regenerate following injury. Following myocardial infarction (MI), cardiomyocytes
undergo massive cell death and through activation of resident cardiac fibroblasts (CFs), are replaced by non-
contractile fibrotic scar, ultimately leading to heart failure. Novel heart failure therapies aimed at promoting
cardiomyocyte regeneration are desperately needed. In recent years, direct reprogramming of resident CFs to
induced cardiac-like myocytes (iCLMs) has emerged as a promising therapeutic strategy to repurpose the fibrotic
response of the injured heart toward a functional myocardium. Direct cardiac reprogramming was initially
achieved through the overexpression of the transcription factors (TFs) Gata4, Mef2c, and Tbx5 (GMT); later,
Hand2 (GHMT) and Akt1 (AGHMT) were found to enhance this process in embryonic and neonatal cell types.
However, these cocktails have demonstrated limited success in reprogramming adult human and mouse
fibroblasts, constraining the clinical translation of this therapy. Our laboratory undertook a screen of mammalian
gene regulatory factors to discover novel regulators of cardiac reprogramming in adult fibroblasts and identified
the histone reader PHF7 as the most potent activating factor. In work currently under revision, we have
demonstrated the ability of PHF7 to markedly activate reprogramming in adult human and mouse fibroblasts by
increasing chromatin accessibility at cardiac super enhancers when added to a five-factor reprogramming
cocktail. However, it is not yet known which transcription factors are necessary for PHF7 to optimally facilitate
adult cardiac reprogramming. Our preliminary data support the overall hypothesis that PHF7 is a critical regulator
of cardiac cell fate conversion and potently reprograms adult fibroblasts to functional cardiomyocytes in vitro and
in vivo in the presence of fewer cardiac transcription factors. To explore this hypothesis, I will address the
following aims: (1) to define the factors necessary to achieve adult cardiac reprogramming with PHF7, and (2)
to define the ability of PHF7 to improve cardiac function following myocardial infarction in vivo. Completion of
these studies will enhance our understanding of the factors necessary to achieve cardiac reprogramming in adult
cell types and elucidate the mechanisms necessary for this conversion. Further, these studies will potentially
provide the basis for development of a novel therapeutic factor in cardiac reprogramming for the treatment of
ischemic heart disease. The proposed studies will be performed in the large and highly productive laboratory of
Dr. Eric N. Olson, PhD at University of Texas Southwestern Medical Center. All studies and career development
will be carried out under the guidance of Dr. Olson, a pioneer in the field of direct cardiac reprogramming.

## Key facts

- **NIH application ID:** 10313560
- **Project number:** 1F32HL160116-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Glynnis Garry Bann
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $42,725
- **Award type:** 1
- **Project period:** 2021-12-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313560

## Citation

> US National Institutes of Health, RePORTER application 10313560, Elucidation of the Role for PHF7 in Direct Reprogramming of Fibroblasts to Cardiomyocytes (1F32HL160116-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10313560. Licensed CC0.

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