# The role of RNA binding proteins in heart development and congenital heart defects

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $719,153

## Abstract

ABSTRACT
 Hypoplastic left heart syndrome (HLHS) is a congenital heart disease with a high mortality rate. Infants with
this syndrome are born with circulation problems due to hypoplasia of the left part of the heart that includes
aorta, left ventricle, mitral valve and aortic valve. Infants may need to undergo a series of open-heart surgeries
to restore systemic circulation. Even after the surgeries, these patients can develop heart failure and other
complications due to the overload on the right ventricle that serves as the single ventricle. Very little is known
about the etiology and pathogenic mechanisms of HLHS. Recent human genetic studies identified de novo
loss of function mutations in the RNA binding protein RBFOX2 that are linked to the HLHS phenotype. It is
currently unknown how RBFOX2 contributes to HLHS developmental defects. This is mainly because of our
lack of knowledge regarding the role of RBFOX2 in cardiovascular development and its target RNAs in the
embryonic heart. Using our Rbfox2 conditional knockout mouse model, which recapitulates several phenotypic,
cellular, and molecular features of HLHS, we will address these urgent and clinically relevant questions utilizing
genetic, molecular/cellular and state-of-the art custom designed sequencing and computational approaches.
Our main goal is to determine the mechanisms by which RBFOX2-regulated RNA networks contribute to
cardiovascular development and investigate their contributions to HLHS. Our work will determine the
underlying mechanisms of HLHS developmental defects caused by loss of RBFOX2. Ultimately, our findings
will advance development of innovative HLHS therapeutic strategies by restoring aberrant RBFOX2-regulated
gene expression in HLHS patients using modified antisense oligonucleotides in the future.

## Key facts

- **NIH application ID:** 10848467
- **Project number:** 5R01HL157780-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** MUGE NESLIHAN KUYUMCU-MARTINEZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $719,153
- **Award type:** 5
- **Project period:** 2023-04-12 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10848467

## Citation

> US National Institutes of Health, RePORTER application 10848467, The role of RNA binding proteins in heart development and congenital heart defects (5R01HL157780-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10848467. Licensed CC0.

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