# Integrating Transcriptome Reprogramming Into Cardiac Plasticity Regulatory Mechanisms

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $430,752

## Abstract

Project Abstract
Programmed terminal differentiation of cardiac myocytes is vital for reorganizing the heart's structure and
function to meet basic physiologic demands. Many of these differentiation mechanisms are redeployed after
ischemic injury or in the context of heart disease. While terminal differentiation is indispensable for basic
cardiac function this fate change is associated with the nearly complete cessation of myocyte proliferation,
which underlies one of the major barriers in the treatment of ischemic heart disease- the lack of effective
therapeutic strategies to remuscularize the fibrotic heart. Many differentiation mechanisms are redeployed after
injury, but it's unclear whether the response is adaptive or pathologic, thus understanding how the flow of
genetic information establishes and maintains myocyte differentiation improves our current knowledge of basic
cardiac physiology and provides insights into cardiac regeneration and disease. Much of our knowledge about
terminal differentiation has come from investigating gene regulatory mechanisms at the level of DNA and
epigenetics with little attention paid to post-transcriptional control of the cardiac transcriptome. Here we are
hijacking the function of a highly conserved RNA-binding protein muscle blind like-1 (MBNL1) to understand
how transcriptional reprogramming of myocyte terminal differentiation impacts post natal development and
post-infarct regenerative and pathologic remodeling. Specifically, this application will use an array of gain and
loss of function mouse models that permit cardiac myocyte specific temporal dosing of MBNL1 to reprogram
the heart's transcriptome to achieve the following aims: (1) determine the role of MBNL1-dependent
transcriptome reprogramming in establishing and maintaining cardiac myocyte differentiation, (2) define the
role of MBNL1-dependent transcriptome reprogramming in post-infarct regenerative and pathologic myocyte
remodeling, and (3) determine context dependent regulatory mechanisms underlying MBNL1-dependent
transcriptome reprogramming. Data from these aims will identify potential mechanisms by which transcriptional
reprogramming can be used to control either endogenous or stem-cell derived myocyte fate as a novel
therapeutic strategy for cardiac remodeling and regeneration.

## Key facts

- **NIH application ID:** 10371248
- **Project number:** 5R01HL141187-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jennifer Michelle Davis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $430,752
- **Award type:** 5
- **Project period:** 2018-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371248

## Citation

> US National Institutes of Health, RePORTER application 10371248, Integrating Transcriptome Reprogramming Into Cardiac Plasticity Regulatory Mechanisms (5R01HL141187-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10371248. Licensed CC0.

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