# Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $11,848

## Abstract

The parent grant, “Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia”, aims to
develop a pharmacologic testing platform for in vitro prediction of drug-induced cardiac
arrhythmia using engineered heart slices (EHS) embedded with human induced pluripotent stem
cell-derived cardiomyocytes (hiPSC-CMs). Aim 1 focuses on improving methods of quantifying
and controlling the maturity of hiPSC-CMs, which is key to the implementation and interpretation
of these models. The work proposed here will supplement Aim 1 of the parent grant by expanding
beyond healthy wildtype hiPSC-CMs to understand maturity in hiPSCs harboring genetic cardiac
disorders, specifically arrhythmogenic right ventricular cardiomyopathy (ARVC). The first aim of
this work is to establish the maturation trajectory of diseased hiPSC-CMs in comparison to
wildtype cells. This will be accomplished by assessing, at several time points, structural features
(i.e. sarcomere organization, troponin isoform expression), CD36 positivity (marker of metabolic
maturity), and transcriptomic entropy scoring (a novel RNA-sequencing based method). The
second aim is to evaluate the effects of targeted metabolic maturation on diseased vs healthy
hiPSC-CMs. We will measure maturity in cells treated with standard differentiation procedures
and media against cells supplemented with a novel nutrient formula shown to boost maturity in
wildtype hiPSC-CMs. By providing insight into the maturational differences of healthy and disease
cells and potentially allowing us to account for that confounding variable, this work will facilitate
the creation of robust disease models for drug response testing and therapeutic development.

## Key facts

- **NIH application ID:** 10250777
- **Project number:** 3R01HL152249-01S2
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** LESLIE TUNG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $11,848
- **Award type:** 3
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10250777

## Citation

> US National Institutes of Health, RePORTER application 10250777, Engineered Human Heart Slice for Testing Drug-Induced Arrhythmia (3R01HL152249-01S2). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10250777. Licensed CC0.

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