# Human Induced Pluripotent Stem Cells for Cardiovascular Disease Modeling

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $691,803

## Abstract

PROJECT SUMMARY
While dilated cardiomyopathy (DCM) is one of the most common hereditary heart diseases, we currently lack
effective and targeted treatments. Cardiac fibrosis is an important hallmark of DCM and the presence of
excessive fibrotic tissues can severely hamper heart function. However, limited information exists on how DCM
mutations can induce cardiac fibrosis in familial DCM patients. This study aims to address this significant
knowledge gap using patient-specific human induced pluripotent stem cells (iPSCs) generated from common
DCM patients. In Aim 1, we will differentiate iPSCs into cardiac fibroblasts (iPSC-CFs) and cardiomyocytes
(iPSC-CMs) to study how cardiomyocyte-specific and non-cardiomyocyte-specific mutations can activate cardiac
fibroblasts. In Aim 2, we will examine whether iPSC-CFs induce cardiac dysfunction through secretory factors
and/or direct interaction with cardiomyocytes using a 3D engineered heart tissues (EHT) platform. In Aim 3, we
will identify gene/mutation-specific druggable targets using state-of-the-art CRISPR/dCas9i (inhibitory) and
CRISPR/dCas9a (activating) technologies, and validate these targets in an established DCM mouse model. By
completing this study, we expect to identify fibrosis-inducing DCM mutations, understand how they activate
cardiac fibroblasts, and potentially discover novel druggable mechanism to manage DCM. Collectively, this multi-
PI R01 study has tremendous translational value to aid future precision cardiovascular medicine.

## Key facts

- **NIH application ID:** 10585979
- **Project number:** 5R01HL113006-11
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Joseph C. Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $691,803
- **Award type:** 5
- **Project period:** 2012-05-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10585979

## Citation

> US National Institutes of Health, RePORTER application 10585979, Human Induced Pluripotent Stem Cells for Cardiovascular Disease Modeling (5R01HL113006-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10585979. Licensed CC0.

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