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Project Title:  The Impact of Spaceflight and Radiation on Clonal Hematopoiesis Reduce
Images: icon  Fiscal Year: FY 2023 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 05/01/2023  
End Date: 04/30/2026  
Task Last Updated: 05/18/2023 
Download Task Book report in PDF pdf
Principal Investigator/Affiliation:   Mason, Christopher  Ph.D. / Weill Medical College of Cornell University 
Address:  1305 York Ave, Room Y13-04, Box 140 
 
New York , NY 10021-5663 
Email: chm2042@med.cornell.edu 
Phone: 203-668-1448  
Congressional District: 12 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Weill Medical College of Cornell University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Bailey, Susan  Ph.D. Colorado State University 
De Vlaminck, Iwijn  Ph.D. Cornell University 
Elemento, Olivier  Ph.D. Weill Medical College of Cornell University 
Hassane, Duane  Ph.D. Weill Medical College of Cornell University 
Levine, Ross  MD Sloan Kettering Institute for Cancer Research 
Project Information: Grant/Contract No. 80NSSC23K0832 
Responsible Center: NASA JSC 
Grant Monitor: Elgart, Robin  
Center Contact: 281-244-0596 (o)/832-221-4576 (m) 
shona.elgart@nasa.gov 
Unique ID: 15495 
Solicitation / Funding Source: 2019-2020 HERO 80JSC019N0001-HHCBPSR, OMNIBUS2: Human Health Countermeasures, Behavioral Performance, and Space Radiation-Appendix C; Omnibus2-Appendix D 
Grant/Contract No.: 80NSSC23K0832 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
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No. of Master's Candidates:  
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Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: None
Human Research Program Gaps: None
Task Description: Clonal hematopoiesis (CH) occurs when blood cells harboring an advantageous mutation propagate faster than others. These mutations can confer a risk for certain hematological cancers and cardiovascular disease. However, little is known about the methods for reducing these clones, nothing is known about CH in astronauts, and there is little information about the proper way to understand and stratify the risk of these mutations that are found in normal individuals.

The goal of this proposal is to delineate the risk of CH for astronauts and other patients using improved, novel methods that map nucleic acids isolated from peripheral blood and urine. We hypothesize that radiation imparts a selective advantage, specifically in hematopoietic cells with DNA Damage Response mutations, and that spaceflight duration and radiation dose can drive and mediate this selection process.

We will use a cohort of >1,100 patients from Weill Cornell Medicine (WCM) with both blood and urine, where 11% already show CH, as well as existing data from healthy cohorts (n=20,000) from the Englander Institute for Precision Medicine (EIPM) and Memorial Sloan Kettering Cancer Center (MSKCC) (n=25,000). We will use established methods for purifying and extracting DNA, using protocols developed for the NASA Twins Study and our published EIPM PreCISE-1 test for CH. This includes 100+ genes involved in clonal hematopoiesis, cancer, and cardiovascular diseases (CVD), sequenced to a depth of >2000x coverage (with unique molecular barcodes), giving >95% sensitivity for variant allele frequencies (VAF) > 1% (about 1/50 cells).

The presence of CH can inform long-term CVD and cancer risk, and thus can serve as a useful metric for astronauts preparing for long-term missions. Also, CH confers a mutation-specific inflammatory risk, which can potentiate post-flight or post-radiation morbidity and be compared to other risk factors. Thus, identifying and managing CH represents a crucial unmet need for astronaut health, radiation risk stratification, and guiding oncology patients more broadly.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2023 
Task Progress: New project for FY2023.

Bibliography: Description: (Last Updated: 06/07/2024) 

Show Cumulative Bibliography
 
 None in FY 2023