# RBPMS, a novel RNA splicing regulator of cardiac function and disease

> **NIH NIH K99** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $100,480

## Abstract

Project Summary/Abstract
Cardiovascular disease is the leading cause of mortality in the US and worldwide. Decades of endeavors in
studying cardiovascular disease have led to a substantial understanding of underlying mechanisms, but there is
still much to be learned. Cardiovascular homeostasis is regulated at both transcriptional and posttranscriptional
levels, and an increasing body of evidence suggests that RNA posttranscriptional modifications, such as
alternative RNA splicing, play essential roles in regulating cardiac function and disease. A previous study by the
applicant (Dr. Peiheng Gan) has revealed that RNA-binding protein with multiple splicing (RBPMS) is crucial for
cardiomyocyte proliferation and heart development through modulating alternative RNA splicing. In the new
study, the applicant found that RBPMS is required for adult cardiac contractility. The absence of RBPMS impaired
cardiomyocyte contractility and impacted the splicing of various sarcomeric genes, which displayed distinct
patterns. Cardiac RBPMS expression was decreased in patients with heart failure and doxorubicin-induced heart
failure in animal models. Intriguingly, the overexpression of RBPMS showed protective effects on contractility
and survival in doxorubicin-treated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
Together, these data suggest that RBPMS is a key regulator of adult heart function and heart failure progression.
During the K99 phase of this proposal (Aim 1), the applicant will characterize how RBPMS regulates
cardiomyocyte contraction through modulating RNA splicing using both mouse models and hiPSC-CMs. In Aim
2, the applicant will leverage cellular and molecular tools to characterize the functional interactions between
RBPMS and other cardiac RNA binding proteins (RBPs), including RBM20 and RBFOX1. This study provides
the applicant with a unique opportunity to investigate how different RBPs interact to regulate cardiac function
and alternative RNA splicing. During the R00 phase (Aim 3), the applicant will explore the therapeutic potential
of overexpressing RBPMS in doxorubicin-induced mouse heart failure and determine the molecular mechanisms
of RBPMS-mediated protective effects. The completion of the proposed study will provide critical insights into
the posttranscriptional regulation of cardiac function by RBPs and create new opportunities for curing
cardiovascular disease.
The applicant will acquire crucial knowledge and skills by studying RBPs and RNA posttranscriptional
modifications during his K99 phase to complement his previous expertise in cardiovascular research. Additionally,
the applicant’s career development will be enhanced by the expertise of an exceptional mentoring and advisory
committee, as well as the unparalleled resources and ample educational and training opportunities at UT
Southwestern Medical Center, a world-class research institution. The outstanding mentoring, unmatched
resources, and strong commi...

## Key facts

- **NIH application ID:** 10984736
- **Project number:** 1K99HL171888-01A1
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Peiheng Gan
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $100,480
- **Award type:** 1
- **Project period:** 2024-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10984736

## Citation

> US National Institutes of Health, RePORTER application 10984736, RBPMS, a novel RNA splicing regulator of cardiac function and disease (1K99HL171888-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10984736. Licensed CC0.

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