Elucidating SEX differences in radiation-induced cardiotoxicity with cell village ipscs
Active Cooperative Agreement Awarded Last action
- Award ID
- U01AI183953
- Recipient
-
The Leland Stanford Junior University UEI HJD6G4D6TJY5
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,623,008
Award facts
- Assistance listing
- 93.310 Trans-NIH Research Support
- Completion date 77% complete
- Funding agency
- Office of the Director National Institutes of Health, Department of Health and Human Services
- Place of performance
- Palo Alto, CA 94305, USA
Award details come from USAspending.gov.
Description
- Abstract
- 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.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $533,448 | |
| Amendment | $550,479 | |
| Original award | $539,081 |
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Colorado State University | $91,633 | |
| Colorado State University | $109,343 |
Quick answers
Who received award U01AI183953?
U01AI183953 was awarded to The Leland Stanford Junior University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on July 19, 2024.
How much is award U01AI183953 worth?
$1,623,008 has been obligated on U01AI183953.
Which agency awarded U01AI183953?
National Institute of Allergy and Infectious Diseases (National Institutes of Health) awarded U01AI183953, with funding from Office of the Director (National Institutes of Health).
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