# Elucidating Electro-Mechanical Dysfunction in Heart Failure with Human Stem Cell Models

> **NIH NIH P01** · STANFORD UNIVERSITY · 2020 · $2,366,100

## Abstract

PROJECT SUMMARY (OVERVIEW)
The overarching goal of this Program Project Grant (PPG) is to better understand the mechanisms by which
altered sodium (Na+) and calcium (Ca2+) signaling contribute to electromechanical dysfunction in heart failure
(HF). Project 1 (Wu) will define the mechanism of Na+-Ca2+ dysregulation leading to arrhythmia in HF and
explore the impact of genetic heterogeneity on this phenomenon in induced pluripotent stem cell-derived
cardiomyocytes (iPSC-CMs) derived from patients with mutations associated with dilated cardiomyopathy
(DCM), which is a major cause of heart failure. Project 2 (Bers) will do parallel mechanistic studies in adult HF
rabbit myocytes and intact hearts to understand how to break the vicious cycle Na+/Ca2+ dysregulation.
Importantly, quantitative mechanistic results will inform and be validated by rabbit and human computational
models. Project 3 (Mercola) will advance these investigations by taking a high-throughput approach to the
electrophysiological phenotypes to elucidate the role of non-ion channel proteins in the cellular dysfunction and
drug-induced arrhythmia, identifying novel therapeutic targets in this pathway, and generate an in silico model
to predict arrhythmia susceptibility. An Administrative Core A (Wu) will support the three projects. Computational
Modeling Core B (Grandi) will support all three projects by creating multi-scale computational models of iPSC-
CMs and adult myocytes and tissues that incorporate patient-specific channel and drug effects. Together, these
cross-disciplinary and synergistic studies will help lead to our goal of “Precision Medicine” for preventing HF and
sudden cardiac death.

## Key facts

- **NIH application ID:** 10006331
- **Project number:** 5P01HL141084-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Joseph C. Wu
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,366,100
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006331

## Citation

> US National Institutes of Health, RePORTER application 10006331, Elucidating Electro-Mechanical Dysfunction in Heart Failure with Human Stem Cell Models (5P01HL141084-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10006331. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*