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Project Title:  DNA Damage in the ISS Astronaut's Lymphocytes and Their Association with Stress-Induced Immune Dysfunction Reduce
Images: icon  Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 01/01/2016  
End Date: 09/30/2022  
Task Last Updated: 10/05/2020 
Download report in PDF pdf
Principal Investigator/Affiliation:   Wu, Honglu  Ph.D. / NASA Johnson Space Center 
Address:  Human Adaptation and Countermeasures Office 
2101 NASA Parkway, Mail Code SK 
Houston , TX 77058-3607 
Email: honglu.wu-1@nasa.gov 
Phone: 281-483-6470  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Feiveson, Alan  Ph.D. NASA Johnson Space Center 
Zhang, Ye  Ph.D. NASA Johnson Space Center 
Moreno-Villanueva, Maria  Ph.D. NASA Johnson Space Center 
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Stenger, Michael  
Center Contact: 281-483-1311 
michael.b.stenger@nasa.gov 
Solicitation / Funding Source: 2014-15 HERO NNJ14ZSA001N-MIXEDTOPICS. Appendix E: Behavioral Health & Human Health Countermeasures Topics 
Grant/Contract No.: Internal Project 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM-101:Evaluate the effects of deep-space radiation on immune dysfunction, as an additional hazard to the effects of psychophysiological stress and weightlessness (IRP Rev L)
(2) IM-105:Identify immune biomarkers that correlate with known spaceflight-related immune dysfunction and immune outcomes, as a first step in designing in-flight monitoring paradigms (IRP Rev L)
Flight Assignment/Project Notes: NOTE: End date changed to 9/30/2023 per NASA JSC. (Ed., 11/18/21)

NOTE: End date changed to 9/30/2022 per PI (Ed., 10/6/20)

NOTE: Extended to 3/31/2021 per PI (March 2019)--Ed., 10/3/19

Task Description: NOTE: This is an integrated project consisting of Dr. Brian Crucian's "Functional Immune Alterations, Latent Herpesvirus Reactivation, Physiological Stress, and Clinical Incidence Onboard the International Space Station" directed research; and Dr. Richard Simpson's "The Impact of an ISS Mission on the Anti-Viral and Functional Properties of NK-cells, T-cells, B-cells and Dendritic Cells," Dr. Kanokporn Rithidech's "Effects of Space Flights on the Proteome of Astronauts' Plasma," and Dr. Honglu Wu's "DNA Damage in the ISS Astronaut's Lymphocytes and Their Association with Stress-Induced Immune Dysfunction" solicited research.

The unique radiation environment encountered in space has been known to cause deleterious effects in humans, and these effects are of special concern for prolonged space missions beyond the protective terrestrial magnetosphere. DNA lesions, namely single- and double-strand breaks, are the most common of these effects and the most likely to compromise health. In addition to radiation, astronauts in space experience microgravity and other stress factors. In human cells, immune cells in particular, stress-induced catecholamine and corticoid release, as well as increased levels of inflammation, are known to induce DNA damage and impair DNA repair, which in turn results in single and double-strand breaks. Intact DNA repair machinery is crucial for immune cell functionality. Therefore understanding the interaction between DNA damage response and immune response is an important step towards improving knowledge of the mechanisms associated with immune dysfunction in the space environment.

In this study, we propose to quantify DNA damage in astronauts’ lymphocytes by measuring the frequency of single- and double-strand breaks. We will also perform RNA-seq analysis with a focus on pathways involved in DNA damage response and/or inflammatory response. Measures of DNA damage obtained before, during, and after long-duration International Space Station (ISS) missions will then be compared with the mRNA levels. The outcomes in the present study will also be compared to the measured T cell function, cytokine profiles and viral reactivation in the Integrated Immune Flight Study, which is the parental project of our proposed study.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2021 
Task Progress: Sample collection.

To date, collection of blood samples has been performed on 10 ISS crewmembers and 10 matching ground controls at all of the 7 (6 for ground controls) time points (L-180, L-45, mid-flight, late-flight, R+0, R+30, and R+90). Collection from the 11th crewmember and the ground control has not begun.

Sample analysis

RNA-seq analysis. Gene expression sample analysis using the RNA-seq technique was completed for 8 ISS crewmembers and 8 matching ground controls.

MicroRNA analysis. MicroRNA sample analysis using the RNA-seq technique was completed for 8 ISS crewmembers and 8 matching ground controls.

PCR analysis. Analysis of expression of DNA damage and immune function related genes using the PCR-array technique was completed for 4 ISS crewmembers and 4 matching ground controls. Supplies to analyse the next set of 4 crewmembers and ground controls have been purchased and received.

DNA damage analysis. DNA damage analysis is being performed at University of Konstanz, Germany.

Data analysis

RNA-seq data. Analysis of RNA-seq data was completed for 4 ISS crewmembers and 4 matching ground controls. Initial bioinformatics analysis of the next set of 4 crewmembers and 4 matching ground controls has begun.

MicroRNA data. Analysis of microRNA data was completed for 4 ISS crewmembers and 4 matching ground controls.

Bibliography Type: Description: (Last Updated: 10/06/2020) 

Show Cumulative Bibliography Listing
 
Articles in Peer-reviewed Journals Moreno-Villanueva M, Zhang Y, Feiveson A, Mistretta B, Pan Y, Chatterjee S, Wu W, Clanton R, Nelman-Gonzalez M, Krieger S, Gunaratne P, Crucian B, Wu H. "Single-cell RNA-sequencing identifies activation of TP53 and STAT1 pathways in human T lymphocyte subpopulations in response to ex vivo radiation exposure." Int J Mol Sci. 2019 May 10;20(9):E2316. https://doi.org/10.3390/ijms20092316 ; PMID: 31083348; PMCID: PMC6539494 , May-2019
Project Title:  DNA Damage in the ISS Astronaut's Lymphocytes and Their Association with Stress-Induced Immune Dysfunction Reduce
Images: icon  Fiscal Year: FY 2018 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 01/01/2016  
End Date: 12/31/2018  
Task Last Updated: 11/29/2017 
Download report in PDF pdf
Principal Investigator/Affiliation:   Wu, Honglu  Ph.D. / NASA Johnson Space Center 
Address:  Human Adaptation and Countermeasures Office 
2101 NASA Parkway, Mail Code SK 
Houston , TX 77058-3607 
Email: honglu.wu-1@nasa.gov 
Phone: 281-483-6470  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Feiveson, Alan  Ph.D. NASA Johnson Space Center 
Zhang, Ye  Ph.D. NASA Johnson Space Center 
Moreno-Villanueva, Maria  Ph.D. NASA Johnson Space Center 
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Baumann, David  
Center Contact:  
david.k.baumann@nasa.gov 
Solicitation / Funding Source: 2014-15 HERO NNJ14ZSA001N-MIXEDTOPICS. Appendix E: Behavioral Health & Human Health Countermeasures Topics 
Grant/Contract No.: Internal Project 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM-101:Evaluate the effects of deep-space radiation on immune dysfunction, as an additional hazard to the effects of psychophysiological stress and weightlessness (IRP Rev L)
(2) IM-105:Identify immune biomarkers that correlate with known spaceflight-related immune dysfunction and immune outcomes, as a first step in designing in-flight monitoring paradigms (IRP Rev L)
Task Description: NOTE: This is an integrated project consisting of Dr. Brian Crucian's "Functional Immune Alterations, Latent Herpesvirus Reactivation, Physiological Stress, and Clinical Incidence Onboard the International Space Station" directed research; and Dr. Richard Simpson's "The Impact of an ISS Mission on the Anti-Viral and Functional Properties of NK-cells, T-cells, B-cells and Dendritic Cells," Dr. Kanokporn Rithidech's "Effects of Space Flights on the Proteome of Astronauts' Plasma," and Dr. Honglu Wu's "DNA Damage in the ISS Astronaut's Lymphocytes and Their Association with Stress-Induced Immune Dysfunction" solicited research.

The unique radiation environment encountered in space has been known to cause deleterious effects in humans, and these effects are of special concern for prolonged space missions beyond the protective terrestrial magnetosphere. DNA lesions, namely single- and double-strand breaks, are the most common of these effects and the most likely to compromise health. In addition to radiation, astronauts in space experience microgravity and other stress factors. In human cells, immune cells in particular, stress-induced catecholamine and corticoid release, as well as increased levels of inflammation, are known to induce DNA damage and impair DNA repair, which in turn results in single and double-strand breaks. Intact DNA repair machinery is crucial for immune cell functionality. Therefore understanding the interaction between DNA damage response and immune response is an important step towards improving knowledge of the mechanisms associated with immune dysfunction in the space environment.

In this study, we propose to quantify DNA damage in astronauts’ lymphocytes by measuring the frequency of single- and double-strand breaks. We will also perform RNA-seq analysis with a focus on pathways involved in DNA damage response and/or inflammatory response. Measures of DNA damage obtained before, during, and after long-duration International Space Station (ISS) missions will then be compared with the mRNA levels. The outcomes in the present study will also be compared to the measured T cell function, cytokine profiles and viral reactivation in the Integrated Immune Flight Study, which is the parental project of our proposed study.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2018 
Task Progress: Collection of the blood samples has been made in 7 ISS astronauts and 7 matching ground control subjects. Only one astronaut (and the matching control subject) had all of the pre-, during, and post-flight collections completed. All together, 30 samples have been collected. Peripheral blood mononuclear cells (PBMC) have been isolated from whole blood for all 30 samples and split in 3 aliquots for SSB (single strand breaks), DSB (double strand breaks), and RNA-seq analysis. Immediately after PBMC isolation, cell viability and apoptosis rate were measured. Impacts of stowage of blood samples at ambient temperature on gene expressions were also tested.

Bibliography Type: Description: (Last Updated: 10/06/2020) 

Show Cumulative Bibliography Listing
 
 None in FY 2018
Project Title:  DNA Damage in the ISS Astronaut's Lymphocytes and Their Association with Stress-Induced Immune Dysfunction Reduce
Images: icon  Fiscal Year: FY 2016 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 01/01/2016  
End Date: 12/31/2018  
Task Last Updated: 08/24/2016 
Download report in PDF pdf
Principal Investigator/Affiliation:   Wu, Honglu  Ph.D. / NASA Johnson Space Center 
Address:  Human Adaptation and Countermeasures Office 
2101 NASA Parkway, Mail Code SK 
Houston , TX 77058-3607 
Email: honglu.wu-1@nasa.gov 
Phone: 281-483-6470  
Congressional District: 22 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Feiveson, Alan  Ph.D. NASA Johnson Space Center 
Zhang, Ye  Ph.D. NASA Johnson Space Center 
Moreno-Villanueva, Maria  Ph.D. NASA Johnson Space Center 
Project Information: Grant/Contract No. Internal Project 
Responsible Center: NASA JSC 
Grant Monitor: Baumann, David  
Center Contact:  
david.k.baumann@nasa.gov 
Solicitation / Funding Source: 2014-15 HERO NNJ14ZSA001N-MIXEDTOPICS. Appendix E: Behavioral Health & Human Health Countermeasures Topics 
Grant/Contract No.: Internal Project 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Immune:Risk of Adverse Health Event Due to Altered Immune Response (IRP Rev F)
Human Research Program Gaps: (1) IM-101:Evaluate the effects of deep-space radiation on immune dysfunction, as an additional hazard to the effects of psychophysiological stress and weightlessness (IRP Rev L)
(2) IM-105:Identify immune biomarkers that correlate with known spaceflight-related immune dysfunction and immune outcomes, as a first step in designing in-flight monitoring paradigms (IRP Rev L)
Task Description: NOTE: This is an integrated project consisting of Dr. Brian Crucian's "Functional Immune Alterations, Latent Herpesvirus Reactivation, Physiological Stress, and Clinical Incidence Onboard the International Space Station" directed research; and Dr. Richard Simpson's "The Impact of an ISS Mission on the Anti-Viral and Functional Properties of NK-cells, T-cells, B-cells and Dendritic Cells," Dr. Kanokporn Rithidech's "Effects of Space Flights on the Proteome of Astronauts' Plasma," and Dr. Honglu Wu's "DNA Damage in the ISS Astronaut's Lymphocytes and Their Association with Stress-Induced Immune Dysfunction" solicited research.

The unique radiation environment encountered in space has been known to cause deleterious effects in humans, and these effects are of special concern for prolonged space missions beyond the protective terrestrial magnetosphere. DNA lesions, namely single- and double-strand breaks, are the most common of these effects and the most likely to compromise health. In addition to radiation, astronauts in space experience microgravity and other stress factors. In human cells, immune cells in particular, stress-induced catecholamine and corticoid release, as well as increased levels of inflammation, are known to induce DNA damage and impair DNA repair, which in turn results in single and double-strand breaks. Intact DNA repair machinery is crucial for immune cell functionality. Therefore understanding the interaction between DNA damage response and immune response is an important step towards improving knowledge of the mechanisms associated with immune dysfunction in the space environment.

In this study, we propose to quantify DNA damage in astronauts’ lymphocytes by measuring the frequency of single- and double-strand breaks. We will also measure expression levels of 90 genes known to be involved in DNA damage response and/or inflammatory pathways. Measures of DNA damage obtained before, during, and after long-duration International Space Station (ISS) missions will then be compared with the mRNA levels of the selected genes. The outcomes in the present study will also be compared to the measured T cell function, cytokine profiles and viral reactivation in the Integrated Immune Flight Study, which is the parental project of our proposed study.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2016 
Task Progress: New project for FY2016.

Bibliography Type: Description: (Last Updated: 10/06/2020) 

Show Cumulative Bibliography Listing
 
 None in FY 2016