# Smyd1's role in regulating disease-induced remodeling and gene expression in the cardiomyocyte per period 09/01/2020-08/31/2021.

> **NIH NIH F32** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $2,500

## Abstract

Project Summary
Heart failure is the leading cause of death in developed countries and is characterized by myocyte growth,
fibrosis and organ remodeling, and is accompanied by transcriptional changes in the myocyte genome. These
global changes in gene expression, which constitute both adaptive and maladaptive reprogramming, are driven
by structural changes in chromatin. Although many epigenetic factors have been identified that influence these
transcriptional changes, the proteins responsible for regulating chromatin and their subsequent effects on
cellular and organ remodeling during heart disease are largely unknown. One key mechanism to alter
chromatin structure is through histone modifications and early studies utilizing histone deacetylase inhibitors
revealed that heart disease progression could be attenuated upon treatment in animal models, although the
ubiquitous expression of these proteins and the non-specific nature of the inhibitors has made them unfeasible
as a therapeutic tool in the heart, thus far. In contrast, Smyd1, is a unique myocyte-specific histone
methyltransferase that regulates gene expression in the cardiomyocyte. It was originally shown to play a role in
early cardiac development, however more recently, we have determined that Smyd1 is differentially regulated
in human heart failure patients and in mouse models of heart disease. In addition, we have demonstrated that
loss of Smyd1 in the adult mouse heart leads to pro-hypertrophic signaling resulting in myocyte growth, fibrosis
and functional decline. Additionally, we examined the two Smyd1 isoforms, Smyd1a and Smyd1b, in isolated
myocytes and showed that Smyd1a overexpression was capable of inhibiting phenylephrine-induced
hypertrophy. To build upon this work I will (Aim 1) determine if overexpression of Smyd1a in the heart is able to
inhibit disease-induced remodeling using a novel transgenic mouse model, and (Aim 2) identify the specific
genes modified by Smyd1 in the genome to regulate hypertrophic signaling in the myocardium using chromatin
immunoprecipitation and next-generation DNA sequencing (ChIP-Seq). This proposal will allow me to
determine the function of Smyd1 in the adult heart, evaluate its role in attenuating heart disease and identify
the molecular mechanisms by which myocyte growth is regulated. Overall these experiments will enhance our
understanding of how global changes in chromatin remodeling are coordinated and how they affect cardiac
phenotype during the development of heart disease.

## Key facts

- **NIH application ID:** 10450278
- **Project number:** 3F32HL144034-03S2
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Marta Szulik
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,500
- **Award type:** 3
- **Project period:** 2018-09-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450278

## Citation

> US National Institutes of Health, RePORTER application 10450278, Smyd1's role in regulating disease-induced remodeling and gene expression in the cardiomyocyte per period 09/01/2020-08/31/2021. (3F32HL144034-03S2). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10450278. Licensed CC0.

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