# Role of DNA methylation in cardiac failure and recovery

> **NIH NIH K23** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2022 · $198,720

## Abstract

PROJECT SUMMARY/ABSTRACT
Heart failure (HF) is a chronic, progressive and irreversible disorder that is associated with significant morbidity,
mortality and expense. However, recovery of cardiac function has been reported in ~15% of HF patients on left
ventricular assist devices (LVADs), which can be significant enough to allow for device explantation. Thus, the
ability to potentiate cardiac recovery would be paradigm-shifting. Identification of factors associated with cardiac
recovery will provide an opportunity to a) focus our efforts aimed at promoting recovery, b) gain insight into the
mechanisms leading to disease progression and reversal, and c) discover new therapeutic targets. My goal in
seeking a Mentored Research Career Development Award is to acquire the necessary training and experience
to pioneer the novel field of epigenomics and genomics of HF by positioning myself as a pivotal translational
integrator in the virtuous cycle of “bedside to bench research and back”. My clinical background along with the
translational research training gained through this proposal, will allow me to orchestrate successful translational
studies by prioritizing gene pathways of high clinical relevance for functional studies and by better standardizing
and integrating clinical and genomic data. This proposal includes a discovery approach to understand the
molecular bases for HF and cardiac recovery (Aim 1) and a predictive approach to design a multivariate model
predictive of cardiac recovery (Aim 2). In Aim 1, we will focus on answering the questions “what gene pathways
are dysregulated in HF” and “does LVAD therapy uniquely alter these gene pathways in responders vs non-
responders” (Aim 1A), for which we will compare DNA methylation and gene expression from myocardium of
HF and non-failing controls, followed by comparisons between pre- and post-LVAD within responders as
compared to non-responders. Next, we will investigate the molecular mechanisms by which DNA methylation
reprograms cardiac metabolism in cardiac recovery. We hypothesize that DNMT3a binds to, and methylates,
specific genetic loci to alter gene expression involved in regulation of glycolysis and oxidative phosphorylation
(Aim 1B). We will perform ChIP-qPCR of DNMT3a in a targeted manner of our already identified gene candidates
(e.g. HADHA, etc.). In Aim 2, we will define the epigenetic predictors of cardiac recovery, by comparing DNA
methylation and gene expression in responders and non-responders at the pre-LVAD timepoint, and will build a
multivariable predictive model including clinical variables. The expertise of our multidisciplinary team, combined
with formal didactics will provide the support needed to achieve my training aims, developing skills in: (1) design
of genetic/epigenetic studies; (2) bioinformatics; and (3) professional development as a PI. In summary, our
research will further our understanding of the mechanisms involved in HF and recovery and lay the foundation
for t...

## Key facts

- **NIH application ID:** 10455474
- **Project number:** 5K23HL150322-03
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Omar Enrique Wever-Pinzon
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $198,720
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10455474

## Citation

> US National Institutes of Health, RePORTER application 10455474, Role of DNA methylation in cardiac failure and recovery (5K23HL150322-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10455474. Licensed CC0.

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