SASHA

In this project, the activity of DNA and RNA-editing enzymes involved in mutations that may be related to development of immune dysfunction-related disease states and cancer will be evaluated by analyzing blood samples taken from the crew before, during, and after spaceflight. This will help better understand changes in editing activity of these enzymes in blood stem cells due to spaceflight. This project is part of the expanded Integrated Space Stem Cell Orbital Reseach (ISSCOR) collaboration between the Sanford Stem Cell Institute, JM Foundation, and Axiom Space.

Research Overview

• SASHA (Ax-2) (Space Hematopoietic Stem Cell Aging (Ax-2)) evaluates whether immune dysregulation of stem cells occurs in human subjects due to spaceflight. Specifically, changes in editing activity of APOBEC and ADAR1 in human hematopoietic stem cells due to spaceflight.
• This investigation assesses ADAR1 and APOBEC activity in hematopoietic stem cells isolated from whole blood samples from human spaceflight subjects returned at ambient temperature.
• Dysregulation of adenosine deaminase acting on ribonucleic acid (ADAR; RNA editing enzyme) and the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC; DNA editing enzyme), has been linked to cancer.
• Whole peripheral blood samples are collected from crew members several times on the Axiom Mission 2 (Ax-2): preflight launch-30 ± 10 days, preflight launch-1 ± 10 day on the International Space Station (ISS) (immediately before egress from the ISS), postflight return+1 ± 10 day, postflight return +30 ± 10 days, postflight return+1 year, with annual sample collection desired up to return+5 years postflight.
• This longitudinal collection of samples allows investigators to study short- and long-term human stem cell immune dysregulation in spaceflight.

Description

SASHA (Ax-2) (Space Hematopoietic Stem Cell Aging (Ax-2)) collects whole blood samples from crew members to evaluate editing enzymes while exposed to spaceflight. Hematopoietic stem cells (HSCs) are the self-renewing cells responsible for reconstituting the entire blood cell pool. HSCs are subject to mutations that may be acquired, among other causes, in an enzymatic and episodic manner through pro-inflammatory cytokine-responsive APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) and ADAR1 (adenosine deaminase acting on RNA 1) activation. APOBEC is a deoxyribonucleic acid (DNA) editing enzyme that deaminates cytosine bases to uracil bases, which are then converted to thymine bases in DNA. ADAR1 is a ribonucleic acid (RNA) editing enzyme that deaminates adenosine bases to inosine, which are then converted to guanine bases in DNA. ADAR1 and APOBEC have been previously shown to be activated in inflammatory disease states and cancer.

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This investigation consists of collecting whole blood samples preflight, on orbit (prior to hatch close), and postflight, with rapid return at ambient temperature for postflight analysis. Investigators will evaluate ADAR1 and APOBEC activity as well as other changes that occur in HSCs due to spaceflight.

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