Responsible Center: NASA JSC
Grant Monitor: Elgart, Robin
Center Contact: 281-244-0596 (o)/832-221-4576 (m)
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
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|| 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.