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Task Book: Biological & Physical Sciences Division and Human Research Program
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Project Title:  Effects of Chronic High LET Radiation on the Human Heart Reduce
Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
TRISH--TRISH 
Start Date: 11/01/2020  
End Date: 10/31/2023  
Task Last Updated: 12/02/2020 
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Principal Investigator/Affiliation:   Weil, Michael  Ph.D. / Colorado State University 
Address:  Department of Environmental & Radiological Health Sciences 
1618 Campus Delivery 
Fort Collins , CO 80521-2807 
Email: michael.weil@colostate.edu 
Phone: 970-491-5902  
Congressional District:
Web:  
Organization Type: UNIVERSITY 
Organization Name: Colorado State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Chatterjee, Anushree  Ph.D. University of Colorado at Boulder 
Brandl, Alexander  Ph.D. Colorado State University 
Chicco, Adam  Ph.D. Colorado State University 
Wu, Joseph  M.D., Ph.D. Stanford University 
Project Information: Grant/Contract No. NNX16AO69A-RAD0105 
Responsible Center: TRISH 
Grant Monitor:  
Center Contact:   
Solicitation / Funding Source: 2020 TRISH Space Radiation Solicitation TSRAD-2020. Translational Research Institute for Space Health (TRISH) Human-Based Models to Study Effects of Space Radiation and Countermeasures 
Grant/Contract No.: NNX16AO69A-RAD0105 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
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Human Research Program Elements: None
Human Research Program Risks: None
Human Research Program Gaps: None
Flight Assignment/Project Notes: NOTE: Start/End dates changed to 11/1/2020 and 10/31/2023, respectively, per E. Urquieta/TRISH (Ed., 9/14/21)

Task Description: We have detected adverse cardiac effects in mice and rats exposed to either high energy (HZE) ions or low dose rate neutrons, radiation exposures which simulate those in space. We propose to extend these findings to an engineered model of human cardiac tissue, identify biomarkers of radiation-induced cardiac damage, and test potential countermeasures against damage. To do this, we have assembled a team of experienced researchers from Colorado State University, Stanford University, and the University of Colorado. We will design and commission a facility that will allow us to expose engineered heart tissue (EHTs) to high linear energy transfer (LET) neutron radiation at low dose rate nearly continuously for more than a month. We will use the facility to irradiate EHTs fabricated using human induced pluripotent stem cells (hiPSCs) differentiated to cardiomyocytes, endothelium, and fibroblasts seeded into a fibrin/collagen-based extracellular matrix scaffold cast between flexible silicon posts. This is a robust physiological tissue model to identify functional and molecular changes, and we have previously flown hiPSC-derived cardiomyocytes aboard the International Space Station (ISS). Additional EHTs will be sham irradiated or irradiated with low dose rate gamma rays. The irradiated tissues will be screened for a panel of functional outcomes with known clinical relevance. Gene expression patterns will be determined to identify pathogenic gene networks that can be targeted with countermeasures, and media supernatants will be collected for metabolomics and proteomic analyses for biomarker discovery. Several small molecule countermeasures will be tested to attenuate adverse outcomes in the irradiated EHT based on published and preliminary studies in rodents and cell models. Among these is aspirin which targets oxidative stress, mitochondrial dysfunction and mtDNA damage, and inflammation implicated in our rodent models. We will also test overexpression of adeno-associated virus (AAV) transduced Nrf2 and antisense peptide nucleic acids (PNAs) directed against gene pathways identified in transcriptomic analyses as a novel and rapid multiplexed genetic countermeasure approach. Results from this proposed study will have the potential to improve risk assessments for space radiation induced cardiovascular disease, lead to methodologies for inflight detection for cardiac damage which, in turn, will inform decisions on whether countermeasures should be administered to individual crew members, and lead to the identification of those countermeasures.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2021 
Task Progress: New project for FY2021.

Bibliography Type: Description: (Last Updated: 07/25/2021)  Show Cumulative Bibliography Listing
 
 None in FY 2021