# The role of YTHDF2 in postnatal cardiac growth and homeostasis

> **NIH NIH F31** · OHIO STATE UNIVERSITY · 2021 · $41,136

## Abstract

PROJECT SUMMARY / ABSTRACT
Cardiomyocytes lose their ability to proliferate postnatally, after which cardiac growth and adaptation to stress
are driven by physiological hypertrophy. While adaptive remodeling can occur in response to injury, persistent
strain on the heart can elicit chronic hypertrophy, maladaptive remodeling and heart failure. Hypertrophy is driven
by structural and functional changes in cardiomyocytes resulting from altered gene expression. While abundant
studies have investigated heart failure pathogenesis at the transcriptional level, investigation into the post-
transcriptional events underlying cardiac homeostasis have only recently emerged. N6-methyladenosine (m6A),
the most abundant mRNA modification, has been shown to play a role in the heart's ability to maintain
homeostasis. YTH domain containing protein 2 (YTHDF2) has been implicated in regulating gene expression
through preferential binding and degradation of mRNAs with the m6A modification. However, the cardiac role of
YTHDF2 is completely unknown. Our goal is to better understand how YTHDF2 functions to impact
cardiomyocyte phenotype and therefore regulate cardiac development and homeostasis. Our preliminary results
hint at regulation of Yes-associated protein (YAP) as key molecular mechanism for YTHDF2-dependent control
of heart homeostasis. YAP is an effector of the Hippo signaling pathway that functions to regulate proliferative
genes. We therefore hypothesize that YTHDF2 regulates postnatal cardiac development and homeostasis via
YAP modulation. In Aim 1, we will induce cardiomyocyte-specific neonatal knockout of YTHDF2 to assess the
impacts of ablation on postnatal cardiac development. In Aim 2, we will characterize the role of YTHDF2 in
modulating YAP activity in the heart. This work will be carried out in the laboratory of Dr. Federica Accornero, an
expert in post-transcriptional regulation of cardiac hypertrophy, and under the co-supervision of Dr. Juan Alfonzo,
a leader in the fields of expert in RNA biology and biochemistry. With successful completion of proposed work,
our research will elucidate a role for YTHDF2 in determining cardiomyocyte phenotype and thus its role in
development and homeostasis of the heart. Our long-term goal is be able to target cardiac m6A and YTHDF2 as
an avenue for improving heart failure patient outcomes.

## Key facts

- **NIH application ID:** 10234362
- **Project number:** 1F31HL158234-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Christopher J. Gilbert
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $41,136
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234362

## Citation

> US National Institutes of Health, RePORTER application 10234362, The role of YTHDF2 in postnatal cardiac growth and homeostasis (1F31HL158234-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10234362. Licensed CC0.

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