# Elucidating Genotype-Phenotype Relationship of Polygenic Dilated Cardiomyopathies

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $121,848

## Abstract

PROJECT SUMMARY
Dilated cardiomyopathy (DCM) is a genetic cardiac disorder with high morbidity and an incidence of 1:250.
Although generally thought of as a disease with monogenic heritability, recent genetic studies suggest
complex polygenic causes. Functional profiles of polygenic cardiomyopathies are poorly understood and this
hampers effective therapeutics development. Recent advances in stem cell technology such as patient-
derived induced pluripotent stem cells (iPSCs) and genome-editing, provides an unprecedented opportunity
to study such disease phenotypes. Cardiomyocytes will be differentiated from iPSCs taken from patients with
two DCM related mutations and sequenced to understand transcriptome differences that may correlate with
disease susceptibility. The analysis will be normalized by using CRISPR to create isogenic controls and also
insert the mutations in healthy individuals that are related to these patients. We will then utilize the iPSC
platform coupled with tissue engineering to develop engineered heart tissues composed of cardiac specific
cells. We will perform single cell RNA sequencing to test the cell-cell interactions and crosstalk between the
cells. We will also perform functional assays like calcium-handling and contractility. CRISPR/dCas9 systems
will allow us to identify genes suitable for drug targeting. The overarching goal of the parent R01 grant is to
understand underlying mechanisms of polygenic DCM using the iPSC platform. The proposed diversity
supplement extends this work by studying patients of different ethnicities and considering how this factors in
disease severity. African-American and Hispanic patients are underrepresented in health studies, and
therefore more vulnerable to poor disease management. Dr. Carlos Vera will expand our cohort of 20
individuals by six iPSC lines derived from these minority populations and perform the proposed set of
experiments.

## Key facts

- **NIH application ID:** 10359919
- **Project number:** 3R01HL130020-06S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** THOMAS QUERTERMOUS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $121,848
- **Award type:** 3
- **Project period:** 2015-12-16 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10359919

## Citation

> US National Institutes of Health, RePORTER application 10359919, Elucidating Genotype-Phenotype Relationship of Polygenic Dilated Cardiomyopathies (3R01HL130020-06S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10359919. Licensed CC0.

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