# Elucidating Sex Differences in Radiation-induced Cardiotoxicity with Cell Village iPSCs

> **NIH NIH U01** · STANFORD UNIVERSITY · 2024 · $539,081

## Abstract

Project Summary
Radiation-Induced Cardiotoxicity (RIC) remains a concerning health issue, particularly in accidental radiation
exposure scenarios as evident in the Life Span Study of Japanese atomic bomb survivors. However, the complex
interplay of factors contributing to the diverse presentations of RIC remains elusive. This project aims to shed
light on the critical roles of sex hormone “estrogen” and genetic variations in estrogen receptor (ER) signaling in
modulating RIC susceptibility and response. The research takes an innovative approach by combining state-of-
the-art techniques and multidisciplinary expertise. Firstly, a "cell village" strategy will be employed which leverage
pooling human induced pluripotent stem cell (iPSC) derivatives from a diverse cohort of 200 individuals. Pooled
iPSCs will be differentiated into 3D cardiac organoids (iPSC-COs) and treated with varying doses of estrogen
and radiation to simulate different physiological conditions and radiation exposure, respectively. Cutting-edge
single-cell genomics and computational technologies will be employed to scrutinize the resulting transcriptomic
and epigenomic changes in each individual. This will help us identify inter-individual variations and underlying
genetic mutations that contribute to differential molecular responses upon irradiation. Additionally, animal models
will be employed to simulate radiological incidences and corroborate multi-omics data to functional outcomes in
whole organisms. Collectively, these experiments will elucidate the genes responsible for sexual disparity in RIC
and its relation to estrogen signaling which can provide insights into personalized risk prediction and intervention
strategies, addressing a critical knowledge gap in the field of radiation biology and cardiovascular health.

## Key facts

- **NIH application ID:** 10923208
- **Project number:** 1U01AI183953-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Adam J Chicco
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $539,081
- **Award type:** 1
- **Project period:** 2024-07-19 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10923208

## Citation

> US National Institutes of Health, RePORTER application 10923208, Elucidating Sex Differences in Radiation-induced Cardiotoxicity with Cell Village iPSCs (1U01AI183953-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10923208. Licensed CC0.

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