# Cardioprotective Therapy for Doxorubicin Using iPSC Microtissue and CRISPR Screening

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $627,358

## Abstract

PROJECT SUMMARY
In tandem with recent improvements in anti-cancer treatment efficacy, cancer treatment-related cardiotoxicity
has become a serious clinical problem. Doxorubicin-induced cardiotoxicity (DIC) is one of the most common
chemotherapy-related cardiotoxicities. Here, combining human induced pluripotent stem cells (iPSCs) with
large-scale CRISPR screening, nanotechnology, and engineered 3D cardiac microtissue technology, we will
develop a pipeline which enables us to identify therapeutic targets and potential chemical compounds that
protect cardiomyocytes from DIC. First, we will perform genome-wide perturbation screening in doxorubicin
resistance using CRISPR technology. It will enable us to identify druggable genes that are causative for DIC or
essential for resistance in DIC. Second, we will perform high-throughput screening of chemical compounds
using nanoparticles. It will enable us to identify cardioprotective chemicals and compile a Cardioprotective
Drug Repurposing Library. Third, we will develop a 3D cardiac microtissue platform that can detect
cardioprotective effects of the candidate therapies. The 3D cardiac microtissue will consist of iPSC-derived
cardiomyocytes, endothelial cells, and fibroblasts, reflective of complex cell-cell interaction and
microenvironment. The goal of this proposal is identify cardioprotective therapy for DIC and to develop
platforms that are expandable to other cancer treatment-related cardiotoxicities.

## Key facts

- **NIH application ID:** 10296896
- **Project number:** 1R01HL150693-01A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** JAYAKUMAR RAJADAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $627,358
- **Award type:** 1
- **Project period:** 2021-08-10 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10296896

## Citation

> US National Institutes of Health, RePORTER application 10296896, Cardioprotective Therapy for Doxorubicin Using iPSC Microtissue and CRISPR Screening (1R01HL150693-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10296896. Licensed CC0.

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