# Gene Modulation of Acetylation Modifiers to Reveal Regulatory Links to Human Cardiac Electromechanics

> **NIH NIH F31** · GEORGE WASHINGTON UNIVERSITY · 2023 · $37,882

## Abstract

PROJECT ABSTRACT
Epigenetic regulation is critical for cardiac electromechanics and pathology. Epigenetic modulators, such as
histone deacetylases (HDACs), are known master regulators of gene expression and influence cardiac function
through chromatin remodeling, direct action on transcription factors (TFs), and action on cytoskeletal and
contractile proteins, among others. Recently, novel pharmacological agents, HDAC inhibitors, have been
developed as treatments for cancer and immune diseases, driving an interest in robust characterization of HDAC
control in cardiac function. Our preliminary experiments focused on computational modeling of RNAi-informed
transcriptomic data in human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) but saw
limitations in knockdown efficiency and loss-of-function-only modulation using siRNAs. To extend and improve
this work, we propose an experimental approach based on bidirectional perturbation (repression/activation) of
individual HDAC genes in hiPSC-CM by CRISPR interference and activation (CRISPRi/a). Transcriptomic
analysis of these samples will inform computational gene regulatory network (GRN) inference to model
relationships between HDACs, TFs, and cardiac ion channels. GRN-predicted relationships will be validated by
all-optical electromechanical assays measuring voltage, calcium, and contraction traces in hiPSC-CM. An
iterative approach will allow feedback from functional experiments to refine our computational models. Such
studies will advance our understanding of how certain HDACs drive electrophysiological phenotypes in the heart,
which is critical in the fields of cardiac injury, cardiac therapeutics, and cardio-oncology.

## Key facts

- **NIH application ID:** 10677295
- **Project number:** 1F31HL168800-01
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** MARIA POZO
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $37,882
- **Award type:** 1
- **Project period:** 2023-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10677295

## Citation

> US National Institutes of Health, RePORTER application 10677295, Gene Modulation of Acetylation Modifiers to Reveal Regulatory Links to Human Cardiac Electromechanics (1F31HL168800-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10677295. Licensed CC0.

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