# Human Induced Pluripotent Stem Cells for Cardiovascular Disease Modeling

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $481,020

## Abstract

PROJECT SUMMARY
Among the familial cardiomyopathies, cardiac laminopathy caused by LMNA mutations accounts for
approximately 6% of all cases. Compared to other DCM patients with left ventricular dilation, LMNA
cardiolaminopathy patients exhibit a severe clinical course, conduction abnormalities, and a high rate of heart
failure. LMNA DCM has a complex pathophysiology and it has been hypothesized that this form of cardiac
disease is due to defects in function of cardiomyocytes (CMs) as well as defects in non-CM populations such
as endothelial cells (ECs). However, the detailed molecular mechanisms of LMNA cardiolaminopathy remain
elusive due to limited patient-derived bio-specimens and lack of appropriate disease models. To overcome
the problem, in this R01 grant renewal application, we will generate human induced pluripotent stem cell-
derived cardiomyocytes (iPSC-CMs) from LMNA DCM patients as well as matched family controls and healthy
unrelated controls. To clarify the detailed molecular mechanisms, we will conduct structural,
electrophysiological, developmental, transcriptome, and mechanistic analyses using patient-specific as well
as genome-edited isogenic iPSC-CMs and iPSC-ECs. Importantly, we will perform drug screening studies
targeting dysregulated signaling pathways. To confirm the beneficial action of identified targeting compounds,
we will then conduct transcriptomic and functional analysis of isogenic LMNA iPSC-CM and iPSC-ECs using
high throughput platforms. Collectively, these studies will uncover mechanistic insights of LMNA
cardiolaminopathy, a major cause of DCM, which may help identify novel therapeutic candidates that can
target CMs and ECs, two key cell populations.

## Key facts

- **NIH application ID:** 9983131
- **Project number:** 5R01HL113006-09
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Joseph C. Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $481,020
- **Award type:** 5
- **Project period:** 2012-05-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983131

## Citation

> US National Institutes of Health, RePORTER application 9983131, Human Induced Pluripotent Stem Cells for Cardiovascular Disease Modeling (5R01HL113006-09). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9983131. Licensed CC0.

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