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Project Title:  Combined Effects of Simulated Microgravity and Space Radiation on Human Cells Reduce
Images: icon  Fiscal Year: FY 2024 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology   | Animal Biology: Vertebrate  
Start Date: 10/26/2018  
End Date: 04/25/2023  
Task Last Updated: 08/21/2023 
Download report in PDF pdf
Principal Investigator/Affiliation:   Hada, Megumi  Ph.D. / Prairie View A&M University 
Address:  College of Arts and Sciences, PO BOX 519, MS-2230, New Science Bldg 
 
Prairie View , TX 77446 
Email: mehada@pvamu.edu 
Phone: 936-261-3155  
Congressional District: 10 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Prairie View A&M University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Wang, Jing  Ph.D. University of Texas MD Anderson Cancer Center 
Takahashi, Akihisa  Ph.D. Gunma University Heavy Ion Medical Center, Japan 
Fujiwara, Keigi  Ph.D. University of Texas MD Anderson Cancer Center 
Project Information: Grant/Contract No. 80NSSC19K0133 
Responsible Center: NASA KSC 
Grant Monitor: Zhang, Ye  
Center Contact: 321-861-3253 
Ye.Zhang-1@nasa.gov 
Unique ID: 12118 
Solicitation / Funding Source: 2016-17 Space Biology (ROSBio) NNH16ZTT001N-FG. App G: Flight and Ground Space Biology Research 
Grant/Contract No.: 80NSSC19K0133 
Project Type: GROUND 
Flight Program:  
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:
Space Biology Element: (1) Cell & Molecular Biology
(2) Animal Biology: Vertebrate
Space Biology Cross-Element Discipline: None
Space Biology Special Category: (1) Cell Culture
(2) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: NOTE: End date changed to 04/25/2023 per NSSC information (Ed., 7/31/23)

NOTE: End date changed to 10/27/2022 per NSSC information (Ed., 9/15/21)

Task Description: Space radiation and microgravity are two major environmental stressors for human in space travel. One of the fundamental questions in space biology research is whether the combined effects of microgravity and exposure to cosmic radiation are synergistic. While studies addressing this question have been carried out for half a century in space or using simulated microgravity on the ground, the reported results are conflicting. Although the reason for the variation in results is not known, it is possible that it may be due to the diversity of biological systems used but more importantly to the experimental designs and hardware used in these studies. For the assessment and management of human health risks in future Moon and Mars Missions, it is necessary to obtain more basic data on the molecular and cellular responses to combined effects of radiation and microgravity.

To establish a firm baseline database, we propose to undertake a systematic study on cultured mammalian cells' responses to the simultaneous insult of radiation and microgravity (both immediate and long term) to elucidate the molecular signaling pathways that lead to these biological effects. The results of the study will provide cellular and molecular biological bases for the assessment and management of human health risks in space.

Recently Dr. Takahashi, co-investigator of this proposal, has developed microgravity-irradiation systems consisting of a 3D clinostat synchronized to the carbon-ion or X-ray irradiation systems. Our new experimental setup allows us to avoid stopping clinostat rotation during irradiation, which was required in all other previous experiments. Gunma University Heavy Ion Medical Center is the only facility in the world where we can expose samples to high-linear energy transfer (LET) irradiation as well as low-LET irradiation under the simulated microgravity condition (i.e., without interrupting clinostat rotation).

Our preliminary data obtained from the use of this new device on gene expression in human fibroblasts show that splicing cycle-related genes and cell cycle related genes are significantly up-regulated and S-phase DNA replication and DNA repair-related genes were down-regulated with C-ion irradiation under simulated microgravity.

In this proposal we will investigate 3 different endpoints from early to late responses in 2 human cell lines using our new devices to study combined effects of microgravity and space radiation. Human fibroblasts and epithelial cells will be exposed to X-rays and C-ions under the simulated microgravity condition (rotated with 3-D clinostat). Control cells will be irradiated in 1G environment (with the static stage). We will investigate the extent of expression of specific proteins and of the post-translational modification states of signaling proteins (Aim 1), gene expressions and the pathways involved (Aim 2), and the extent of chromosome aberrations (Aim 3) caused by the combined effects of simulated microgravity and radiation. To investigate from the early to late endpoints in the same cell types will provide cellular and molecular biological data that are needed to understand the impact of combined effects of simulated microgravity and space radiation on human health. One of the selected endpoints is chromosome aberration, which is a well-established biomarker for cancer risk and has been used by NASA for the risk assessment of astronauts. Studying this endpoint allows us to compare our results to the astronauts' data after their International Space Station missions.

Completion of this proposal will allow us to determine how the combination of microgravity and radiation will affect the transcriptomic, metabolomic, and proteomic states of cells as well as heritable changes in DNA. These finding will allow us to help develop the countermeasures for the future space missions.

Research Impact/Earth Benefits: Completion of this proposal will allow us to determine how the combination of microgravity and radiation will affect the transcriptomic, metabolomic, and proteomic states of cells as well as heritable changes in DNA. These findings will allow us to help develop the countermeasure for the future space missions.

Task Progress & Bibliography Information FY2024 
Task Progress: Gene Expressions:

1BR-hTERT human fibroblast cells were cultured under 1 gravity (1G) or simulated µG for 48 hrs in total and collected 0 (sham-irradiated), 3 or 24 hrs after X-ray or Carbon-ion (C-ion) irradiation. A three-dimensional clinostat was used to accomplish the simulation of µG and the simultaneous radiation exposure of the samples. In total, 36 samples were analyzed (12 conditions in triplicates). The raw transcriptomic data produced from these studies were reanalyzed in the current work, applying a systems biology approach, to identify all differentially expressed genes (DEG) between various conditions and the predominant processes they participate in, and to identify a possible synergy between radiation and µG. RNAseq, employing DESeq2, was the method used to produce lists of differentially expressed genes between different biological conditions. Over-representation analyses were performed in order to identify the enriched biological pathways and targeting transcription factors in up- and down-regulated genes from each DEG analysis.

Comparing sham-irradiated cells under simulated µG and 1G conditions, terms related to response to oxygen levels and muscle contraction were identified. After irradiation with 1Gy of X-ray or C-ion or simulated µG condition, CDKN1A, MDM2, PURPL, PTCHD4, TP53INP1, PAPPA and BTG2 were found to be over-expressed, while MKI67, CCNB1, histone clustered genes, and minichromosome maintenance genes were found to be under-expressed. Prevailing biological processes in DEGs upon irradiation were related to DNA damage repair, signal transduction by p53 class mediator, cell cycle arrest, and apoptosis.

Chromosome Aberrations (CA):

We have also reported our newly established "Simulator of the environments on the Moon and Mars with Neutron-irradiation and Gravity change" (“SwiNG”), for in vitro experiments (Takahashi et al., 2020) in last year’s report. [Ed. Note: See Cumulative Bibliography for complete reference.] Samples can be exposed to neutrons at a low-dose-rate (0.5 mGy/day) using Californium-252 in the center of the centrifuge.

In this study, using this new device, human fibroblasts 1BR-hTERT were exposed to low dose neutrons for 5 days under the simulated outer space (µG), the Moon (1/6G), and Mars (3/8G) condition for 5 days, and chromosomes were collected by using the premature chromosome condensation methods. Chromosomes were analyzed with 3-color whole-chromosome FISH staining. Cells exposed to radiation and partial gravity simultaneously showed higher frequencies of CA compared to exposed to radiation under 1G.

Bibliography: Description: (Last Updated: 02/07/2024) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Hada M, Ikeda H, Saganti PB, Takahashi A. "Increased chromosome aberrations in human cells exposed simultaneously to simulated microgravity and neutrons." 38th Annual Meeting of the American Society for Gravitational and Space Research, Houston, TX, November 9-12, 2022.

Abstracts. 38th Annual Meeting of the American Society for Gravitational and Space Research, Houston, TX, November 9-12, 2022. , Nov-2022

Abstracts for Journals and Proceedings Ikeda H, Hada M, Takahashi A. "Expression profile of cell cycle / aging-related genes in human fibroblasts exposed simultaneously to radiation and simulated microgravity. " 38th Annual Meeting of the American Society for Gravitational and Space Research, Houston, TX, November 9-12, 2022.

Abstracts. 38th Annual Meeting of the American Society for Gravitational and Space Research, Houston, TX, November 9-12, 2022. , Nov-2022

Abstracts for Journals and Proceedings Ju Z, Wang J, Hada M, Takahashi A, Fujiwara K. "The early proteomic responses of cells exposed to simulated microgravity." 38th Annual Meeting of the American Society for Gravitational and Space Research, Houston, TX, November 9-12, 2022.

Abstracts. 38th Annual Meeting of the American Society for Gravitational and Space Research, Houston, TX, November 9-12, 2022. , Nov-2022

Abstracts for Journals and Proceedings Takahashi A, Ikeda H, Mao J-H, Saganti PB, Hada M. "Chromosome aberration induction by simulation environment of outer space, Moon and Mars." 2nd Annual Meeting of the Japanese Society for Quantum Medical Science, Tsukuba, Japan, December 9-10, 2022.

Abstracts. 2nd Annual Meeting of Japanese Society for Quantum Medical Science, Tsukuba, Japan, December 9-10, 2022. , Dec-2022

Abstracts for Journals and Proceedings Hada M, Ikeda H, Mao J-H, Saganti PB, Takahashi A. "Chromosome aberrations in human cells induced by being simultaneously exposed to partial gravity and low dose-rate neutrons." 2023 NASA Human Research Program Investigators’ Workshop, “To the Moon: The Next Golden Age of Human Spaceflight”, Galveston, TX, February 7-9, 2023.

Abstracts. 2023 NASA Human Research Program Investigators’ Workshop, “To the Moon: The Next Golden Age of Human Spaceflight”, Galveston, TX, February 7-9, 2023. , Feb-2023

Abstracts for Journals and Proceedings Malatesta P, Ikeda H, Takahashi2 A, Hada M, Georgakilas AG, Michalopoulos I. "Differential gene expression in human fibroblasts simultaneously exposed to radiation and simulated microgravity." 2023 NASA Human Research Program Investigators’ Workshop, “To the Moon: The Next Golden Age of Human Spaceflight”, Galveston, TX, February 7-9, 2023.

Abstracts. 2023 NASA Human Research Program Investigators’ Workshop, “To the Moon: The Next Golden Age of Human Spaceflight”, Galveston, TX, February 7-9, 2023. , Feb-2023

Abstracts for Journals and Proceedings Takahashi A, Ikeda H, Mao J-H, Saganti PB, Hada M. "Ground simulation experiment: Chromosome aberration frequencies due to space radiation exposure on the Moon and Mars." 12th Annual Meeting of the International Society of Radiation Neurobiology, Niigata, Japan, March 4-5, 2023.

Abstracts. 12th Annual Meeting of International Society of Radiation Neurobiology, Niigata, Japan, March 4-5, 2023. , Mar-2023

Abstracts for Journals and Proceedings Hada M, Mao J-H, Saganti PB, Takahashi A. "Combined effect of partial gravity and low dose-rate neutrons on human cells." 17th International Congress of Radiation Research, Montréal, Quebec, Canada, August 27-30, 2023.

Abstracts. 17th International Congress of Radiation Research, Montréal, Quebec, Canada, August 27-30, 2023. , Aug-2023

Articles in Peer-reviewed Journals Malatesta P, Kyriakidis K, Hada M, Ikeda H, Takahashi A, Saganti PB, Georgakilas AG, Michalopoulos I. "Differential gene expression in human fibroblasts simultaneously exposed to ionizing radiation and simulated microgravity." Biomolecules. 2024 Jan 10;14(1):88. https://doi.org/10.3390/biom14010088 ; PMID: 38254688; PMCID: PMC10812944 , Jan-2024
Project Title:  Combined Effects of Simulated Microgravity and Space Radiation on Human Cells Reduce
Images: icon  Fiscal Year: FY 2023 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology   | Animal Biology: Vertebrate  
Start Date: 10/26/2018  
End Date: 10/27/2022  
Task Last Updated: 11/07/2022 
Download report in PDF pdf
Principal Investigator/Affiliation:   Hada, Megumi  Ph.D. / Prairie View A&M University 
Address:  College of Arts and Sciences, PO BOX 519, MS-2230, New Science Bldg 
 
Prairie View , TX 77446 
Email: mehada@pvamu.edu 
Phone: 936-261-3155  
Congressional District: 10 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Prairie View A&M University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Wang, Jing  Ph.D. University of Texas MD Anderson Cancer Center 
Takahashi, Akihisa  Ph.D. Gunma University Heavy Ion Medical Center, Japan 
Fujiwara, Keigi  Ph.D. University of Texas MD Anderson Cancer Center 
Project Information: Grant/Contract No. 80NSSC19K0133 
Responsible Center: NASA KSC 
Grant Monitor: Zhang, Ye  
Center Contact: 321-861-3253 
Ye.Zhang-1@nasa.gov 
Unique ID: 12118 
Solicitation / Funding Source: 2016-17 Space Biology (ROSBio) NNH16ZTT001N-FG. App G: Flight and Ground Space Biology Research 
Grant/Contract No.: 80NSSC19K0133 
Project Type: GROUND 
Flight Program:  
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:
Space Biology Element: (1) Cell & Molecular Biology
(2) Animal Biology: Vertebrate
Space Biology Cross-Element Discipline: None
Space Biology Special Category: (1) Cell Culture
(2) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: NOTE: End date changed to 10/27/2022 per NSSC information (Ed., 9/15/21)

Task Description: Space radiation and microgravity are two major environmental stressors for human in space travel. One of the fundamental questions in space biology research is whether the combined effects of microgravity and exposure to cosmic radiation are synergistic. While studies addressing this question have been carried out for half a century in space or using simulated microgravity on the ground, the reported results are conflicting. Although the reason for the variation in results is not known, it is possible that it may be due to the diversity of biological systems used but more importantly to the experimental designs and hardware used in these studies. For the assessment and management of human health risks in future Moon and Mars Missions, it is necessary to obtain more basic data on the molecular and cellular responses to combined effects of radiation and microgravity.

To establish a firm baseline database, we propose to undertake a systematic study on cultured mammalian cells' responses to the simultaneous insult of radiation and microgravity (both immediate and long term) to elucidate the molecular signaling pathways that lead to these biological effects. The results of the study will provide cellular and molecular biological bases for the assessment and management of human health risks in space.

Recently Dr. Takahashi, co-investigator of this proposal, has developed microgravity-irradiation systems consisting of a 3D clinostat synchronized to the carbon-ion or X-ray irradiation systems. Our new experimental setup allows us to avoid stopping clinostat rotation during irradiation, which was required in all other previous experiments. Gunma University Heavy Ion Medical Center is the only facility in the world where we can expose samples to high-linear energy transfer (LET) irradiation as well as low-LET irradiation under the simulated microgravity condition (i.e., without interrupting clinostat rotation).

Our preliminary data obtained from the use of this new device on gene expression in human fibroblasts show that splicing cycle-related genes and cell cycle related genes are significantly up-regulated and S-phase DNA replication and DNA repair-related genes were down-regulated with C-ion irradiation under simulated microgravity.

In this proposal we will investigate 3 different endpoints from early to late responses in 2 human cell lines using our new devices to study combined effects of microgravity and space radiation. Human fibroblasts and epithelial cells will be exposed to X-rays and C-ions under the simulated microgravity condition (rotated with 3-D clinostat). Control cells will be irradiated in 1G environment (with the static stage). We will investigate the extent of expression of specific proteins and of the post-translational modification states of signaling proteins (Aim 1), gene expressions and the pathways involved (Aim 2), and the extent of chromosome aberrations (Aim 3) caused by the combined effects of simulated microgravity and radiation. To investigate from the early to late endpoints in the same cell types will provide cellular and molecular biological data that are needed to understand the impact of combined effects of simulated microgravity and space radiation on human health. One of the selected endpoints is chromosome aberration, which is a well-established biomarker for cancer risk and has been used by NASA for the risk assessment of astronauts. Studying this endpoint allows us to compare our results to the astronauts' data after their International Space Station missions.

Completion of this proposal will allow us to determine how the combination of microgravity and radiation will affect the transcriptomic, metabolomic, and proteomic states of cells as well as heritable changes in DNA. These finding will allow us to help develop the countermeasures for the future space missions.

Research Impact/Earth Benefits: Completion of this proposal will allow us to determine how the combination of microgravity and radiation will affect the transcriptomic, metabolomic, and proteomic states of cells as well as heritable changes in DNA. These findings will allow us to help develop the countermeasure for the future space missions.

Task Progress & Bibliography Information FY2023 
Task Progress: Post-translational modification of proteins To identify post-translational modification (PTM), as well as changes in protein expression levels, we used a high throughput method called reverse-phase protein array (RPPA), which is available at the University of Texas MD Anderson Cancer Center. This method uses an array of close to 500 well-characterized antibodies, to which proteins in cell lysates will bind, and the amount of bound proteins to each antibody is quantified. Needless to say, many of the antibodies are against post-translationally modified proteins. Before exposing cells to both radiation and µG, we first analyzed how cells respond to altered gravitational environments. In this year, we have completed the manuscript of the changes in expression and modification of protein after gravity changes with actin dynamics.

Gene expressions On the basis of our RNA sequencing (RNA-seq) results, we are proceeding data analysis focusing on human aging-related genes. Specifically, 84 genes encoding key molecules involved in human aging were selected with information from the RT2 Profiler PCR Array panel (QIAGEN polymerase chain reaction/PCR array panel), including several functions (e.g., genomic instability, inflammatory response, cellular senescence, cytoskeleton regulator, oxidative stress, transcriptional regulation, and epigenetics alterations). After combined treatment with C-ion irradiation and simulated µG, the expressions of collagen, type I, alpha 1 (COL1A1) and collagen, type III, alpha 1 (COL3A1), known as cytoskeleton regulators, were decreased (3 h, 24 h); and transcriptional regulation related genes (PHF3 and SMAD2) and DNA binding/RNA binding related gene ZFR (Zinc Finger RNA Binding Protein) were increased. A manuscript is under preparation.

Chromosome aberrations We have reported our newly established "Simulator of the environments on the Moon and Mars with Neutron-irradiation and Gravity change" (SwiNG), for in vitro experiments (Takahashi et al., 2020) in last year’s report. Samples can be exposed to neutrons at a low-dose-rate (0.5 mGy/day) using Californium-252 in the center of the centrifuge. In this year, using this new device, human fibroblasts 1BR-hTERT were exposed to low dose neutrons for 5 days under simulated space (µG), Moon (1/6G), and Mars (3/8G) conditions for 5 days, and chromosomes were collected by using the premature chromosome condensation methods. Chromosome aberration (CA) analysis with 3-color whole-chromosome Fluorescence In Situ Hybridization (FISH) staining is in progress.

Bibliography: Description: (Last Updated: 02/07/2024) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Takahashi A, Ikeda H, Hada M. "Chromosome aberration induction by simultaneous exposure of partial gravity and low dose-rate neutrons using SwiNG." The 36th Annual Meeting of the Japanese Biology Space Science Society, Gifu, Japan, September 16-18, 2022.

Abstracts. The 36th Annual Meeting of the Japanese Biology Space Science Society, Gifu, Japan, September 16-18, 2022. , Sep-2022

Abstracts for Journals and Proceedings Takahashi A, Ikeda H, Hada M. "Chromosome aberration induction by simultaneous exposure of partial gravity and low dose-rate neutrons simulating outer space, the Moon, and Mars." The 65th Annual Meeting of the Japanese Radiation Research Society, Osaka, Japan, September 15-17, 2022.

Abstracts. The 65th Annual Meeting of the Japanese Radiation Research Society, Osaka, Japan, September 15-17, 2022. , Sep-2022

Abstracts for Journals and Proceedings Ikeda H, Hada M, Takahashi A. "The synergistic effects of radiation and simulated microgravity to expression profile changes of cell cycle / aging-related genes in human fibroblasts." The 65th Annual Meeting of the Japanese Radiation Research Society, Osaka, Japan, September 15-17, 2022.

Abstracts. The 65th Annual Meeting of the Japanese Radiation Research Society, Osaka, Japan, September 15-17, 2022. , Sep-2022

Abstracts for Journals and Proceedings Takahashi A, Ikeda H, Guiriuis FNL, Yoshida Y, Hada M. "Simulator of the environments on the Moon and Mars with neutron-irradiation and gravity-change (SwiNG). " 44th COSPAR Scientific Assembly 2022, Athens, Greece, July 16-24, 2022.

Abstracts. 44th COSPAR Scientific Assembly 2022, Athens, Greece, July 16-24, 2022. , Jul-2022

Abstracts for Journals and Proceedings Hada M, Ikeda H, Plante I, Mao JH, Saganti P, Takahashi A. "Increased chromosome aberrations in human cells exposed to simulated microgravity and radiation simultaneously." 44th COSPAR Scientific Assembly 2022, Athens, Greece, July 16-24, 2022.

Abstracts. 44th COSPAR Scientific Assembly 2022, Athens, Greece, July 16-24, 2022. , Jul-2022

Abstracts for Journals and Proceedings Ikeda H, Hada M, Takahashi A. "Expression profile of cell cycle or aging-related genes in human fibroblasts exposed simultaneously to radiation and simulated microgravity." 44th COSPAR Scientific Assembly 2022, Athens, Greece, July 16-24, 2022.

Abstracts. 44th COSPAR Scientific Assembly 2022, Athens, Greece, July 16-24, 2022. , Jul-2022

Abstracts for Journals and Proceedings Takahashi A. "My future dream through 'Living in Space'." The 11th Annual Meeting of the International Society of Radiation Neurobiology, Virtual, March 19, 2022.

Abstracts. The 11th Annual Meeting of the International Society of Radiation Neurobiology, Virtual, March 19, 2022. , Mar-2022

Abstracts for Journals and Proceedings Guirguis FNL, Yamanouchi S, Takeuchi K, Takahashi S, Tashiro M, Hidema J, Higashitani A, Adachi T, Zhang S, Yoshida Y, Nagamatsu A, Hada M, Takeuchi K, Takahashi T, Sekitomi Y, Takahashi A. "Development of the Simulator of the environments on the Moon and Mars with Neutron-irradiation and Gravity-change (SwiNG)." The 11th Annual Meeting of the International Society of Radiation Neurobiology, Virtual, March 19, 2022.

Abstracts. The 11th Annual Meeting of the International Society of Radiation Neurobiology, Virtual, March 19, 2022. , Mar-2022

Abstracts for Journals and Proceedings Ikeda H, Hada M, Takahashi A. "Comprehensive gene expression analysis of human fibroblasts using 3D clinostat synchronized irradiation systems." 2022 NASA Human Research Program Investigators’ Workshop, Virtual, February 7-10, 2022.

Abstracts. 2022 NASA Human Research Program Investigators’ Workshop, Virtual, February 7-10, 2022. , Feb-2022

Abstracts for Journals and Proceedings Takahashi A, Yamanouchi S, Takeuchi K, Takahashi S, Tashiro M, Hidema J, Higashitani A, Adachi T, Zhang S, Guirguis FNL, Yoshida Y, Nagamatsu A, Hada M, Takeuchi K, Takahashi T, Sekitomi Y. "SwiNG: Combined-environment simulator of Moon and Mars." 2022 NASA Human Research Program Investigators’ Workshop, Virtual, February 7-10, 2022.

Abstracts. 2022 NASA Human Research Program Investigators’ Workshop, Virtual, February 7-10, 2022. , Feb-2022

Abstracts for Journals and Proceedings Ju Z, Chiu Y-J, Thomas TN, Yamanouchi S, Yoshida Y, Abe J, Takahashi A, Wang J, Fujiwara K, Hada M. "Early responses of cultured mammalian cells to altered gravitational vector: Adaptation to microgravity and changes in cell motility." 2022 NASA Human Research Program Investigators’ Workshop, Virtual, February 7-10, 2022.

Abstracts. 2022 NASA Human Research Program Investigators’ Workshop, Virtual, February 7-10, 2022. , Feb-2022

Abstracts for Journals and Proceedings Takahashi A, Suzuki K, Tsuruoka C, Morioka T, Takeshima T, Yoshida Y, Nakamura A, Ikeda H, Hada M, Nagamatsu A, Ohira Y, Inatomi Y, Kakinuma S. "Research on combined effects of space radiation and variable gravity - 2021 Annual Report." The 36th Annual Meeting of the Space Environment Utilization Symposium, Virtual, January 18-19, 2022.

Abstracts. The 36th Annual Meeting of the Space Environment Utilization Symposium, Virtual, January 18-19, 2022. , Jan-2022

Abstracts for Journals and Proceedings Ikeda H, Hada M, Takahashi A. "Combined effects of HZE particle and simulated µG on gene expression in human fibroblasts." Japanese Society for Quantum Medical Science, Virtual, December 10-11, 2021.

Abstracts. Japanese Society for Quantum Medical Science, Virtual, December 10-11, 2021. , Dec-2021

Abstracts for Journals and Proceedings Hada M, Yamanouchi S, Mao J-H, Ikeda H, Plante I, Saganti PB, Takahashi A. "Increases of chromosome aberrations in human cells exposed simultaneously to simulated microgravity and radiation." 37th Annual Meeting of the American Society for Gravitational and Space Research, Baltimore, MD, November 3-6, 2021.

Abstracts. 37th Annual Meeting of the American Society for Gravitational and Space Research, Baltimore, MD, November 3-6, 2021. , Nov-2021

Abstracts for Journals and Proceedings Yamanouchi S, Adachi T, Yoshida Y, Rhone J, Mao J-H, Fujiwara K, Saganti PB, Takahashi A, Hada M. "The increases of chromosome aberration in human peripheral blood lymphocytes exposed to simulated microgravity and radiation simultaneously." Kitakanto Medical Society Annual Meeting, Maebashi, Japan, September 30-Oct 1, 2021.

Abstracts. Kitakanto Medical Society Annual Meeting, Maebashi, Japan, September 30-Oct 1, 2021. , Sep-2021

Abstracts for Journals and Proceedings Yamanouchi S, Adachi T, Yoshida Y, Rhone J, Mao J-H, Fujiwara K, Saganti PB, Takahashi A, Hada M. "Chromosome aberrations in human peripheral blood lymphocytes exposed simultaneously to radiation and simulated microgravity." The 64th Annual Meeting of the Japanese Radiation Research Society, Mito, Japan, September 22-24, 2021.

Abstracts. The 64th Annual Meeting of the Japanese Radiation Research Society, Mito, Japan, September 22-24, 2021. , Sep-2021

Abstracts for Journals and Proceedings Yamanouchi S, Adachi T, Yoshida Y, Rhone J, Mao J-H, Fujiwara K, Saganti PB, Takahashi A, Hada M. "Combined exposure to radiation and simulated microgravity increases chromosome aberration in human peripheral blood lymphocytes." The 35th Annual Meeting of Japanese Society for Biological Science in Space, Kanazawa, Japan, September 24-26, 2021.

Abstracts. The 35th Annual Meeting of Japanese Society for Biological Science in Space, Kanazawa, Japan, September 24-26, 2021. , Sep-2021

Articles in Peer-reviewed Journals Beheshti A, McDonald JT, Hada M, Takahashi A, Mason CE, Mognato M. "Genomic changes driven by radiation-induced DNA damage and microgravity in human cells." Int J Mol Sci. 2021 Oct;22(19):10507. Review. https://doi.org/10.3390/ijms221910507 ; PMID: 34638848 PMCID: PMC8508777 , Oct-2021
Articles in Peer-reviewed Journals Ju Z, Thomas TN, Chiu YJ, Yamanouchi S, Yoshida Y, Abe JI, Takahashi A, Wang J, Fujiwara K, Hada M. "Adaptation and changes in actin dynamics and cell motility as early responses of cultured mammalian cells to altered gravitational vector." Int J Mol Sci. 2022 May 30;23(11):6127. https://doi.org/10.3390/ijms23116127 ; PMID: 35682810; PMCID: PMC9181735 , May-2022
Awards Yamanouchi S, Adachi T, Yoshida Y, Rhone J, Mao J-H, Fujiwara K, Saganti, PB, Takahashi A, Hada M. "Kitakanto Medical Society Annual Meeting. Best Poster Presentation Award, September 2021. " Sep-2021
Awards Yamanouchi S, Adachi T, Yoshida Y, Rhone J, Mao J-H, Fujiwara K, Saganti PB, Takahashi A, Hada M. "The 35th Annual Meeting of Japanese Society for Biological Science in Space, Best Presentation Award, September 2021." Sep-2021
Awards Guirguis FNL. "President’s Award for Outstanding Research, Gunma University Graduate School of Medicine, March 2022." Mar-2022
Project Title:  Combined Effects of Simulated Microgravity and Space Radiation on Human Cells Reduce
Images: icon  Fiscal Year: FY 2022 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology   | Animal Biology: Vertebrate  
Start Date: 10/26/2018  
End Date: 10/27/2022  
Task Last Updated: 08/27/2021 
Download report in PDF pdf
Principal Investigator/Affiliation:   Hada, Megumi  Ph.D. / Prairie View A&M University 
Address:  College of Arts and Sciences, PO BOX 519, MS-2230, New Science Bldg 
 
Prairie View , TX 77446 
Email: mehada@pvamu.edu 
Phone: 936-261-3155  
Congressional District: 10 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Prairie View A&M University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Wang, Jing  Ph.D. University of Texas MD Anderson Cancer Center 
Takahashi, Akihisa  Ph.D. Gunma University Heavy Ion Medical Center, Japan 
Fujiwara, Keigi  Ph.D. University of Texas MD Anderson Cancer Center 
Project Information: Grant/Contract No. 80NSSC19K0133 
Responsible Center: NASA KSC 
Grant Monitor: Zhang, Ye  
Center Contact: 321-861-3253 
Ye.Zhang-1@nasa.gov 
Unique ID: 12118 
Solicitation / Funding Source: 2016-17 Space Biology (ROSBio) NNH16ZTT001N-FG. App G: Flight and Ground Space Biology Research 
Grant/Contract No.: 80NSSC19K0133 
Project Type: GROUND 
Flight Program:  
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:
Space Biology Element: (1) Cell & Molecular Biology
(2) Animal Biology: Vertebrate
Space Biology Cross-Element Discipline: None
Space Biology Special Category: (1) Cell Culture
(2) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: NOTE: End date changed to 10/27/2022 per NSSC information (Ed., 9/15/21)

Task Description: Space radiation and microgravity are two major environmental stressors for human in space travel. One of the fundamental questions in space biology research is whether the combined effects of microgravity and exposure to cosmic radiation are synergistic. While studies addressing this question have been carried out for half a century in space or using simulated microgravity on the ground, the reported results are conflicting. Although the reason for the variation in results is not known, it is possible that it may be due to the diversity of biological systems used but more importantly to the experimental designs and hardware used in these studies. For the assessment and management of human health risks in future Moon and Mars Missions, it is necessary to obtain more basic data on the molecular and cellular responses to combined effects of radiation and microgravity.

To establish a firm baseline database, we propose to undertake a systematic study on cultured mammalian cells' responses to the simultaneous insult of radiation and microgravity (both immediate and long term) to elucidate the molecular signaling pathways that lead to these biological effects. The results of the study will provide cellular and molecular biological bases for the assessment and management of human health risks in space.

Recently Dr. Takahashi, co-investigator of this proposal, has developed microgravity-irradiation systems consisting of a 3D clinostat synchronized to the carbon-ion or X-ray irradiation systems. Our new experimental setup allows us to avoid stopping clinostat rotation during irradiation, which was required in all other previous experiments. Gunma University Heavy Ion Medical Center is the only facility in the world where we can expose samples to high-linear energy transfer (LET) irradiation as well as low-LET irradiation under the simulated microgravity condition (i.e., without interrupting clinostat rotation).

Our preliminary data obtained from the use of this new device on gene expression in human fibroblasts show that splicing cycle-related genes and cell cycle related genes are significantly up-regulated and S-phase DNA replication and DNA repair-related genes were down-regulated with C-ion irradiation under simulated microgravity.

In this proposal we will investigate 3 different endpoints from early to late responses in 2 human cell lines using our new devices to study combined effects of microgravity and space radiation. Human fibroblasts and epithelial cells will be exposed to X-rays and C-ions under the simulated microgravity condition (rotated with 3-D clinostat). Control cells will be irradiated in 1G environment (with the static stage). We will investigate the extent of expression of specific proteins and of the post-translational modification states of signaling proteins (Aim 1), gene expressions and the pathways involved (Aim 2), and the extent of chromosome aberrations (Aim 3) caused by the combined effects of simulated microgravity and radiation. To investigate from the early to late endpoints in the same cell types will provide cellular and molecular biological data that are needed to understand the impact of combined effects of simulated microgravity and space radiation on human health. One of the selected endpoints is chromosome aberration, which is a well-established biomarker for cancer risk and has been used by NASA for the risk assessment of astronauts. Studying this endpoint allows us to compare our results to the astronauts' data after their International Space Station missions.

Completion of this proposal will allow us to determine how the combination of microgravity and radiation will affect the transcriptomic, metabolomic, and proteomic states of cells as well as heritable changes in DNA. These finding will allow us to help develop the countermeasures for the future space missions.

Research Impact/Earth Benefits: Completion of this proposal will allow us to determine how the combination of microgravity and radiation will affect the transcriptomic, metabolomic, and proteomic states of cells as well as heritable changes in DNA. These findings will allow us to help develop the countermeasure for the future space missions.

Task Progress & Bibliography Information FY2022 
Task Progress: Post-translational modification of proteins. Gravity is a vector, having both directionality and magnitude. During the 2nd year of investigation, we studied cellular response to µG. Under the µG condition, the gravity vector becomes virtually 0, losing both directionality and magnitude. In the 3rd year, we studied whether cells are able to respond only to changes in the gravity directionality. To answer this question, we cultured mammalian cells (mouse 3T3 cells and human and bovine endothelial cells) in tissue culture dishes and then the dishes were flipped upside down for up to 2 hours. We studied the upside down cells by microscopy and reverse-phase protein array (RPPA). Cultured cells were harvested after 0 (no flipping), 10, and 30 min of being upside down, and cell lysates were made. These lysates were then submitted to the MD Anderson’s Proteomics Core for RPPA analyses using the standard array consisting of 488 antibodies. These data are now being analyzed. A manuscript preparation is under way.

Gene expressions

On the basis of our RNA-seq results, we are proceeding data analysis focusing on human aging-related genes. Nine genes (ARIDIA, CIS, COL1A1, COL3A1, PHF3, SMAD2, TPP1, TXNIP, ZFR) were calculated by considering the effect of simulated µG alone.

Chromosome aberrations

Using µG-irradiation system, human whole blood was exposed to X-rays and carbon ions under the simulated µG condition, and chromosomes of lymphocytes were collected with the premature chromosome condensation method in the first mitosis. Chromosome aberrations (CA) were quantified by the 3-color fluorescent in situ hybridization method. Cells exposed to irradiation under the simulated µG condition showed a higher frequency of both simple and complex type of CA compared to cells irradiated under the static condition by either X-rays or carbon-ions. Manuscript has been published with these results (See Biol Sci Space listing in Bibliography section below).

Bibliography: Description: (Last Updated: 02/07/2024) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Ikeda H, Muratani M, Hidema J, Hada M, Fujiwara K, Souda H, Yoshida Y, Takahashi A. "3D clinostat synchronized irradiation systems and expression profile changes of cell cycle-related genes in human fibroblasts." Presented at the 63rd Annual Meeting of the Japanese Radiation Research Society (JRRS), Fukushima Japan (Virtual Meeting), October 15-16, 2020.

Abstract book of Japanese Radiation Research Society (JRRS) 2020 meeting, October 2020. , Oct-2020

Abstracts for Journals and Proceedings Yamanouchi S, Takeuchi K, Takahashi S, Tashiro M, Hidema J, Higashitani A, Adachi T, Zhang S, Guirguis FNL, Yoshida Y, Nagamatsu A, Hada M, Takeuchi K, Takahashi T, Sekitomi Y, Takahashi A. "Development of combined-environment simulator for low-dose-rate radiation and partial gravity of Moon and Mars." Presented at the 63rd Annual Meeting of the Japanese Radiation Research Society (JRRS), Fukushima Japan (Virtual Meeting), October 15-16, 2020.

Abstract book of Japanese Radiation Research Society (JRRS) 2020 meeting, October 2020. , Oct-2020

Abstracts for Journals and Proceedings Hada M, Yamanouchi S, Ikeda H, Rhone JR, Plante I, Fujiwara K, Saganti PB, Takahashi A. "Increased chromosome aberrations in cultured human fibroblasts and lymphoblastic cells exposed simultaneously to simulated microgravity and radiation." Presented at the 66th Annual Meeting of Radiation Research Society, Virtual Meeting, October 18-21, 2020.

Abstract Book. 66th Annual Meeting of Radiation Research Society, Virtual Meeting, October 18-21, 2020. , Oct-2020

Abstracts for Journals and Proceedings Hada M, Yamanouchi S, Rhone JR, Mao J-H, Ikeda H, Plante I, Fujiwara K, Saganti PB, Takahashi A. "Increases chromosome aberrations in human cells exposed simultaneously to simulated microgravity and radiation." Presented at 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021.

Abstract Book. 2021 NASA Human Research Program Investigators’ Workshop, Virtual, February 1-4, 2021. , Feb-2021

Abstracts for Journals and Proceedings Takahashi A, Yamanouchi S, Takeuchi K, Takahashi S, Tashiro M, Hidema J, Higashitani A, Adachi T, Zhang S, Guirguis FNL, Yoshida Y, Nagamatsu A, Hada M, Takeuchi K, Takahashi T, Sekitomi Y. "Development of equipment simulating deep space, Moon and Mars." Presented at the 32nd Conference of the Japan Society of Microgravity Application, Virtual, October 7, 2020.

Abstract Book. 2nd Conference of the Japan Society of Microgravity Application, October 7, 2020. , Oct-2020

Abstracts for Journals and Proceedings Takahashi, Suzuki K, Chizuru C, Morioka T, Takeshima T, Yoshida Y, Nakamura A, Ikeda H, Hada M, Nagamatsu A, Ohira Y, Inatomi Y, Kakinuma S. "Research on Combined Effects of Space Radiation and Variable Gravity – 2020 Annual Report. " Presented at the 35th Space Utilization Symposium, Virtual, January 19, 2021.

Abstract book of Space Utilization Symposium 2021, January 2021 , Jan-2021

Abstracts for Journals and Proceedings Takahashi A. "Does cancer progress in space?" Presented at the Committee on Space Research (COSPAR) 2021-Hybrid, 43rd Scientific Assembly, Sydney, Australia, January 28-February 4, 2021.

Abstract book of COSPAR 2021, January 28-February 4, 2021. , Feb-2021

Articles in Peer-reviewed Journals Yamanouchi S, Adachi T, Yoshida Y, Rhone J, Mao J-H, Fujiwara K, Saganti PB, Takahashi A, Hada M. "The combined effect of simulated microgravity and radiation on chromosome aberrations in human peripheral blood lymphocytes." Biol Sci Space. 2021;35:15-23. https://doi.org/10.2187/bss.35.15 , Aug-2021
Awards Yamanouchi S. "President’s award for outstanding research, Gunma University Graduate School of Medicine, March 2021." Mar-2021
Dissertations and Theses Yamanouchi S. "Simultaneous exposure of cultured human lymphoblastic cells to simulated microgravity and radiation increases chromosome aberrations." Masters dissertation, Gunma University Graduate School of Medicine, Maebashi, Japan, March 2021. , Mar-2021
Project Title:  Combined Effects of Simulated Microgravity and Space Radiation on Human Cells Reduce
Images: icon  Fiscal Year: FY 2021 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology   | Animal Biology: Vertebrate  
Start Date: 10/26/2018  
End Date: 10/25/2021  
Task Last Updated: 08/27/2020 
Download report in PDF pdf
Principal Investigator/Affiliation:   Hada, Megumi  Ph.D. / Prairie View A&M University 
Address:  College of Arts and Sciences, PO BOX 519, MS-2230, New Science Bldg 
 
Prairie View , TX 77446 
Email: mehada@pvamu.edu 
Phone: 936-261-3155  
Congressional District: 10 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Prairie View A&M University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Wang, Jing  Ph.D. University of Texas MD Anderson Cancer Center 
Takahashi, Akihisa  Ph.D. Gunma University Heavy Ion Medical Center, Japan 
Fujiwara, Keigi  Ph.D. University of Texas MD Anderson Cancer Center 
Project Information: Grant/Contract No. 80NSSC19K0133 
Responsible Center: NASA KSC 
Grant Monitor: Zhang, Ye  
Center Contact: 321-861-3253 
Ye.Zhang-1@nasa.gov 
Unique ID: 12118 
Solicitation / Funding Source: 2016-17 Space Biology (ROSBio) NNH16ZTT001N-FG. App G: Flight and Ground Space Biology Research 
Grant/Contract No.: 80NSSC19K0133 
Project Type: GROUND 
Flight Program:  
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:
Space Biology Element: (1) Cell & Molecular Biology
(2) Animal Biology: Vertebrate
Space Biology Cross-Element Discipline: None
Space Biology Special Category: (1) Cell Culture
(2) Translational (Countermeasure) Potential
Task Description: Space radiation and microgravity are two major environmental stressors for human in space travel. One of the fundamental questions in space biology research is whether the combined effects of microgravity and exposure to cosmic radiation are synergistic. While studies addressing this question have been carried out for half a century in space or using simulated microgravity on the ground, the reported results are conflicting. Although the reason for the variation in results is not known, it is possible that it may be due to the diversity of biological systems used but more importantly to the experimental designs and hardware used in these studies. For the assessment and management of human health risks in future Moon and Mars Missions, it is necessary to obtain more basic data on the molecular and cellular responses to combined effects of radiation and microgravity.

To establish a firm baseline database, we propose to undertake a systematic study on cultured mammalian cells' responses to the simultaneous insult of radiation and microgravity (both immediate and long term) to elucidate the molecular signaling pathways that lead to these biological effects. The results of the study will provide cellular and molecular biological bases for the assessment and management of human health risks in space.

Recently Dr. Takahashi, co-investigator of this proposal, has developed microgravity-irradiation systems consisting of a 3D clinostat synchronized to the carbon-ion or X-ray irradiation systems. Our new experimental setup allows us to avoid stopping clinostat rotation during irradiation, which was required in all other previous experiments. Gunma University Heavy Ion Medical Center is the only facility in the world where we can expose samples to high-linear energy transfer (LET) irradiation as well as low-LET irradiation under the simulated microgravity condition (i.e., without interrupting clinostat rotation).

Our preliminary data obtained from the use of this new device on gene expression in human fibroblasts show that splicing cycle-related genes and cell cycle related genes are significantly up-regulated and S-phase DNA replication and DNA repair-related genes were down-regulated with C-ion irradiation under simulated microgravity.

In this proposal we will investigate 3 different endpoints from early to late responses in 2 human cell lines using our new devices to study combined effects of microgravity and space radiation. Human fibroblasts and epithelial cells will be exposed to X-rays and C-ions under the simulated microgravity condition (rotated with 3-D clinostat). Control cells will be irradiated in 1G environment (with the static stage). We will investigate the extent of expression of specific proteins and of the post-translational modification states of signaling proteins (Aim 1), gene expressions and the pathways involved (Aim 2), and the extent of chromosome aberrations (Aim 3) caused by the combined effects of simulated microgravity and radiation. To investigate from the early to late endpoints in the same cell types will provide cellular and molecular biological data that are needed to understand the impact of combined effects of simulated microgravity and space radiation on human health. One of the selected endpoints is chromosome aberration, which is a well-established biomarker for cancer risk and has been used by NASA for the risk assessment of astronauts. Studying this endpoint allows us to compare our results to the astronauts' data after their International Space Station missions.

Completion of this proposal will allow us to determine how the combination of microgravity and radiation will affect the transcriptomic, metabolomic, and proteomic states of cells as well as heritable changes in DNA. These finding will allow us to help develop the countermeasures for the future space missions.

Research Impact/Earth Benefits: Completion of this proposal will allow us to determine how the combination of microgravity and radiation will affect the transcriptomic, metabolomic, and proteomic states of cells as well as heritable changes in DNA. These findings will allow us to help develop the countermeasure for the future space missions.

Task Progress & Bibliography Information FY2021 
Task Progress: Post-translational modification of proteins: Human fibroblasts (1BR-hTERT) were exposed to simulated µG for 0, 15, 30, 60, 120, 240, 480, and 1440 min at Gunma University and total 37 protein samples were collected (4-5 samples for each time points). All samples were shipped to MD Anderson Cancer Center. Reverse-phase protein arrays analysis was performed using a panel of 453 antibodies. 36 proteins whose levels of phosphorylation or expression were statistically different between cells exposed vs not exposed to simulated microgravity for 15 – 480 min. A total of 10 reverse-phase protein array (RPPA) events were downregulated while 26 were upregulated. Interestingly, the protein events that are known to promote cell motility and actin cytoskeleton dynamics were activated at early time points.

Our study so far indicates that 1) Cells appear to adapt to microgravity within hours, 2) phosphorylation of proteins that promote cell migration increases transiently when cells are exposed to microgravity, and 3) actin dynamics is sensitive to gravity and may be involved in gravity sensing. These results were presented as a poster at the 2020 NASA Human Research Program Investigators’ Workshop, and a manuscript is under preparation describing these findings.

Gene expressions: Human fibroblasts (1BR-hTERT) were maintained under standing or rotating conditions for 3 or 24 h after synchronized C-ion or X-ray irradiation at 1 Gy as part of a total culture time of 2 days. Among 57,773 genes analyzed with RNA sequencing, we focused particularly on the expression of 82 cell cycle-related genes after exposure to the radiation and simulated µG. The expression of cell cycle-suppressing genes (ABL1 and CDKN1A) decreased and that of cell cycle-promoting genes (MKI67, KPNA2, CCNB1, STMN1, and MCM4) increased after C-ion irradiation under µG. The cell cycle may pass through the G1/S and G2 checkpoints with DNA damage due to the combined effects of C-ions and µG, suggesting that increased genomic instability might occur in space. Manuscript with these results has been published in Int J Mol Sci (see Cumulative Bibliography).

On the basis of our RNA-seq results, we are proceeding data analysis focusing on human aging-related genes. Specifically, 84 genes encoding key molecules involved in human aging were selected with information of RT2 Profiler PCR Array panel (Qiagen, Hilden, Germany) including several function (e.g., genomic instability, inflammatory response, cellular senescence, cytoskeleton regulator, oxidative stress, transcriptional regulation, and epigenetics alterations). By narrowing down the genes according to statistical criteria, pathway analysis is ongoing.

Chromosome aberrations: Using µG-irradiation system, human lymphoblast TK6 were exposed to X-rays (0.5, 1.1, and 1.5 Gy) and carbon ions (0.25 and 0.5 Gy) under the simulated µG condition, and chromosomes were collected with the premature chromosome condensation method in the first mitosis. Chromosome aberrations (CA) were quantified by the 3-color fluorescent in situ hybridization method. Cells exposed to irradiation under the simulated µG condition showed a higher frequency of both simple and complex type of CA compared to cells irradiated under the static condition by either X-rays or carbon-ions. Manuscript has been prepared with these results and submitted to Life (Ed. note: now published; see Bibliography section).

Bibliography: Description: (Last Updated: 02/07/2024) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Takahashi A, Ikeda H, Muratani M, Hidema J, Hada M, Fujiwara K, Souda H, Yoshida Y. "Combined effects of radiation and microgravity: RNAseq analysis." Presented at the 33rd Annual Meeting of Japanese Society for Biological Science in Space, Chiba, Japan, September 21-22, 2019.

Abstract book. 33rd Annual Meeting of Japanese Society for Biological Science in Space, Chiba, Japan, September 21-22, 2019. , Sep-2019

Abstracts for Journals and Proceedings Yamanouchi S, Rhone J, Takahashi A, Hada M. "Chromosome Aberrations in lymphoblastoid cells exposed simultaneously to simulated microgravity and radiation." Presented at the 33rd Annual Meeting of Japanese Society for Biological Science in Space, Chiba, Japan, September 21-22, 2019.

Abstract book. 33rd Annual Meeting of Japanese Society for Biological Science in Space, Chiba, Japan, September 21-22, 2019. , Sep-2019

Abstracts for Journals and Proceedings Fujiwara K, Hada M, Takahashi A. "Gravity sensing by cells and effects of simultaneous exposure of cells to microgravity and irradiation on chromosomes." Presented at the 9th Annual World Congress of Molecular and Cell Biology-Exploring the Essence of Life for a Better Future, Singapore, Oct. 25 – 27, 2019.

Abstract book. 9th Annual World Congress of Molecular and Cell Biology-Exploring the Essence of Life for a Better Future, Singapore, Oct. 25 – 27, 2019. , Oct-2019

Abstracts for Journals and Proceedings Yamanouchi S, Rhone JR, Takahashi A, Hada M. "Increased chromosome aberrations in lymphoblast cells exposed to radiation under simulated microgravity." Presented at the 62nd Annual Meeting of the Japanese Radiation Research Society, Kyoto, Japan, November 11-16, 2019.

Abstract book. 62nd Annual Meeting of the Japanese Radiation Research Society, Kyoto, Japan, November 11-16, 2019. , Nov-2019

Abstracts for Journals and Proceedings Hada M, Rhone JR, Beitman A, Ikeda H, Plante I, H. Souda H, Yoshida Y, Held KD, Fujiwara K, Saganti PB, Takahashi A. "Increased Chromosome Aberrations in cells exposed simultaneously to simulated microgravity and radiation." Presented at the 35th Annual Meeting of the American Society for Gravitational and Space Research, Denver, CO, November 20-23, 2019.

Abstracts. 35th Annual Meeting of the American Society for Gravitational and Space Research, Denver, CO, November 20-23, 2019. , Nov-2019

Abstracts for Journals and Proceedings Takahashi A, Ikeda H, Muratani M, Hidema J, Hada M, Fujiwara K, Souda H, Yoshida Y. "Expression profile of cell cycle-related genes in human fibroblasts exposed simultaneously to radiation and simulated microgravity." Presented at the 35th Annual Meeting of the American Society for Gravitational and Space Research, Denver, CO, November 20-23, 2019.

Abstracts. 35th Annual Meeting of the American Society for Gravitational and Space Research, Denver, CO, November 20-23, 2019. , Nov-2019

Abstracts for Journals and Proceedings Takahashi A, Kambe R, Suzuki K, Tsuruoka C, Morioka T, Takeshima T, Yoshida Y, Nakamura A, Hada M, Nagamatsu A, Ohira Y, Kakinuma S. "Research on combined effects of space radiation and variable gravity." Presented at the 34th Symposium on Utilization of the Space Environment, Sagamihara, Japan, January 21-22, 2020.

Abstract book. 34th Symposium on Utilization of the Space Environment, Sagamihara, Japan, January 21-22, 2020. , Jan-2020

Abstracts for Journals and Proceedings Yamanouchi S, Rhone J, Takahashi A, Hada M. "Increased chromosome aberrations in lymphoblastoid cells exposed simultaneously to simulated microgravity and radiation." Presented at 2020 NASA Human Research Program Investigators’ workshop, Galveston, TX, January 27-30, 2020.

Abstracts. 2020 NASA Human Research Program Investigators’ workshop, Galveston, TX, January 27-30, 2020. , Jan-2020

Abstracts for Journals and Proceedings Takahashi A, Ikeda H, Muratani M, Hidema J, Fujiwara K, Souda H, Yoshida Y, Hada M. "RNA sequencing of cell cycle-related genes in human fibroblasts exposed simultaneously to radiation and simulated microgravity." Presented at 2020 NASA Human Research Program Investigators’ workshop, Galveston, TX, January 27-30, 2020.

Abstracts. 2020 NASA Human Research Program Investigators’ workshop, Galveston, TX, January 27-30, 2020. , Jan-2020

Abstracts for Journals and Proceedings Fujiwara K, Takahashi A, Wang J, Ju Z, Yoshida Y, Yamanouchi S, Hada M. "Increased protein phosphorylation and actin dynamics as early response in cells exposed to gravity changes." Presented at 2020 NASA Human Research Program Investigators’ workshop, Galveston, TX, January 27-30, 2020.

Abstracts. 2020 NASA Human Research Program Investigators’ workshop, Galveston, TX, January 27-30, 2020. , Jan-2020

Abstracts for Journals and Proceedings Yamanouchi S, Rhone J, Takahashi A, Hada M. "Chromosome aberration assays in lymphoblastoid cells using a 3D clinostat with synchronized irradiation systems." Presented at 2nd Living in Space Meeting, Tokyo Japan, February 27-29, 2020.

Abstract book. 2nd Living in Space Meeting, Tokyo Japan, February 27-29, 2020. , Feb-2020

Articles in Peer-reviewed Journals Furukawa S, Nagamatsu A, Nenoi M, Fujimori A, Kakinuma S, Katsube T, Wang B, Tsuruoka C, Shirai T, Nakamura AJ, Sakaue-Sawano A, Miyawaki A, Harada H, Kobayashi M, Kobayashi J, Kunieda T, Funayama T, Suzuki M, Miyamoto T, Hidema J, Yoshida Y, Takahashi A. "Space radiation biology for 'Living in Space.' " Biomed Res Int. 2020 Apr 8;2020:4703286. Review. https://doi.org/10.1155/2020/4703286 ; PMID: 32337251; PMCID: PMC7168699 , Apr-2020
Articles in Peer-reviewed Journals Yamanouchi S, Rhone J, Mao JH, Fujiwara K, Saganti PB, Takahashi A, Hada M. "Simultaneous exposure of cultured human lymphoblastic cells to simulated microgravity and radiation increases chromosome aberrations." Life (Basel). 2020 Sep 10;10(9):E187. https://doi.org/10.3390/life10090187 ; PMID: 32927618 , Sep-2020
Articles in Peer-reviewed Journals Takahashi A, Yamanouchi S, Takeuchi K, Takahashi S, Tashiro M, Hidema J, Higashitani A, Adachi T, Zhang S, Guirguis FNL, Yoshida Y, Nagamatsu A, Hada M, Takeuchi K, Takahashi T, Sekitomi Y. "Combined environment simulator for low-dose-rate radiation and partial gravity of Moon and Mars." Life (Basel). 2020 Nov 6;10(11):E274. https://doi.org/10.3390/life10110274 ; PMID: 33172150; PMCID: PMC7694743 , Nov-2020
Project Title:  Combined Effects of Simulated Microgravity and Space Radiation on Human Cells Reduce
Images: icon  Fiscal Year: FY 2020 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology   | Animal Biology: Vertebrate  
Start Date: 10/26/2018  
End Date: 10/25/2021  
Task Last Updated: 08/19/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Hada, Megumi  Ph.D. / Prairie View A&M University 
Address:  College of Arts and Sciences, PO BOX 519, MS-2230, New Science Bldg 
 
Prairie View , TX 77446 
Email: mehada@pvamu.edu 
Phone: 936-261-3155  
Congressional District: 10 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Prairie View A&M University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Wang, Jing  Ph.D. University of Texas MD Anderson Cancer Center 
Takahashi, Akihisa  Ph.D. Gunma University Heavy Ion Medical Center, Japan 
Fujiwara, Keigi  Ph.D. University of Texas MD Anderson Cancer Center 
Project Information: Grant/Contract No. 80NSSC19K0133 
Responsible Center: NASA KSC 
Grant Monitor: Zhang, Ye  
Center Contact: 321-861-3253 
Ye.Zhang-1@nasa.gov 
Unique ID: 12118 
Solicitation / Funding Source: 2016-17 Space Biology (ROSBio) NNH16ZTT001N-FG. App G: Flight and Ground Space Biology Research 
Grant/Contract No.: 80NSSC19K0133 
Project Type: GROUND 
Flight Program:  
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:
Space Biology Element: (1) Cell & Molecular Biology
(2) Animal Biology: Vertebrate
Space Biology Cross-Element Discipline: None
Space Biology Special Category: (1) Cell Culture
(2) Translational (Countermeasure) Potential
Task Description: Space radiation and microgravity are two major environmental stressors for human in space travel. One of the fundamental questions in space biology research is whether the combined effects of microgravity and exposure to cosmic radiation are synergistic. While studies addressing this question have been carried out for half a century in space or using simulated microgravity on the ground, the reported results are conflicting. Although the reason for the variation in results is not known, it is possible that it may be due to the diversity of biological systems used but more importantly to the experimental designs and hardware used in these studies. For the assessment and management of human health risks in future Moon and Mars Missions, it is necessary to obtain more basic data on the molecular and cellular responses to combined effects of radiation and microgravity.

To establish a firm baseline database, we propose to undertake a systematic study on cultured mammalian cells' responses to the simultaneous insult of radiation and microgravity (both immediate and long term) to elucidate the molecular signaling pathways that lead to these biological effects. The results of the study will provide cellular and molecular biological bases for the assessment and management of human health risks in space.

Recently Dr. Takahashi, co-investigator of this proposal, has developed microgravity-irradiation systems consisting of a 3D clinostat synchronized to the carbon-ion or X-ray irradiation systems. Our new experimental setup allows us to avoid stopping clinostat rotation during irradiation, which was required in all other previous experiments. Gunma University Heavy Ion Medical Center is the only facility in the world where we can expose samples to high-linear energy transfer (LET) irradiation as well as low-LET irradiation under the simulated microgravity condition (i.e., without interrupting clinostat rotation).

Our preliminary data obtained from the use of this new device on gene expression in human fibroblasts show that splicing cycle-related genes and cell cycle related genes are significantly up-regulated and S-phase DNA replication and DNA repair-related genes were down-regulated with C-ion irradiation under simulated microgravity.

In this proposal we will investigate 3 different endpoints from early to late responses in 2 human cell lines using our new devices to study combined effects of microgravity and space radiation. Human fibroblasts and epithelial cells will be exposed to X-rays and C-ions under the simulated microgravity condition (rotated with 3-D clinostat). Control cells will be irradiated in 1G environment (with the static stage). We will investigate the extent of expression of specific proteins and of the post-translational modification states of signaling proteins (Aim 1), gene expressions and the pathways involved (Aim 2), and the extent of chromosome aberrations (Aim 3) caused by the combined effects of simulated microgravity and radiation. To investigate from the early to late endpoints in the same cell types will provide cellular and molecular biological data that are needed to understand the impact of combined effects of simulated microgravity and space radiation on human health. One of the selected endpoints is chromosome aberration, which is a well-established biomarker for cancer risk and has been used by NASA for the risk assessment of astronauts. Studying this endpoint allows us to compare our results to the astronauts' data after their International Space Station missions.

Completion of this proposal will allow us to determine how the combination of microgravity and radiation will affect the transcriptomic, metabolomic, and proteomic states of cells as well as heritable changes in DNA. These finding will allow us to help develop the countermeasures for the future space missions.

Research Impact/Earth Benefits: Completion of this proposal will allow us to determine how the combination of microgravity and radiation will affect the transcriptomic, metabolomic, and proteomic states of cells as well as heritable changes in DNA. These findings will allow us to help develop the countermeasure for the future space missions.

Task Progress & Bibliography Information FY2020 
Task Progress: Post-translational modification of proteins: Human fibroblasts (1BR-hTERT) were exposed to simulated µG for 0, 15, 30, 60, 120, 240, 480, and 1440 min at Gunma University and total 37 protein samples were collected (4-5 samples for each time points). All samples were shipped to MD Anderson Cancer Center. Currently reverse-phase protein arrays analysis is ongoing for these samples using a panel of 100 antibodies, most of which are targeted to posttranslational modification (PTM) of signaling molecules.

Gene expressions: Human fibroblasts (1BR-hTERT) were maintained under standing or rotating conditions for 3 or 24 h after synchronized C-ion or X-ray irradiation at 1 Gy as part of a total culture time of 2 days. Among 57,773 genes analyzed with RNA sequencing, we focused particularly on the expression of 82 cell cycle-related genes after exposure to the radiation and simulated µG. The expression of cell cycle-suppressing genes (ABL1 and CDKN1A) decreased and that of cell cycle-promoting genes (MKI67, KPNA2, CCNB1, STMN1, and MCM4) increased after C-ion irradiation under µG. The cell cycle may pass through the G1/S and G2 checkpoints with DNA damage due to the combined effects of C-ions and µG, suggesting that increased genomic instability might occur in space. Manuscript has been prepared for these results and submitted to Int J Mol Sci.

Chromosome aberrations: Using µG-irradiation system, human fibroblasts were exposed to X-rays (0.5 Gy, 1.5 Gy) and carbon ions (0.5 Gy) under the simulated µG condition, and chromosomes were collected with the premature chromosome condensation method in the first mitosis. Chromosome aberrations (CA) were quantified by the 3-color fluorescent in situ hybridization method. Cells exposed to irradiation under the simulated µG condition showed a higher frequency of both simple and complex type of CA compared to cells irradiated under the static condition by either X-rays or carbon-ions. Manuscript has been prepared for these results and published on Int J Mol Sci (see Bibliography section).

Bibliography: Description: (Last Updated: 02/07/2024) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Rhone JR, Beitman A, Ikeda H, Plante I, Souda H, Yoshida Y, Held KD, Fujiwara K, Takahashi A, Saganti PB, Hada M. "Increased chromosome aberrations in cells exposed simultaneously to simulated microgravity and radiation." 2019 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2019.

Abstract book. 2019 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2019. , Jan-2019

Abstracts for Journals and Proceedings Takahashi A. "Future space experiments for “cancer risk assessment” in the ISS and the Gateway." International Symposium on Space Medicine & Medical Engineering 2019, Kiryu, Japan, March 20, 2019.

Abstract book. International Symposium on Space Medicine & Medical Engineering 2019, Kiryu, Japan, March 20, 2019. , Mar-2019

Abstracts for Journals and Proceedings Hada M. "Collaborative Research – Combined effects of simulated microgravity and space radiation on human cells." International Symposium on Living in Space 2019, Kyoto, Japan, March 15, 2019.

Abstract book. International Symposium on Living in Space 2019, Kyoto, Japan, March 15, 2019. , Mar-2019

Abstracts for Journals and Proceedings Takahashi A. "Gunma University Heavy Ion Medical Center (GHMC): Therapy and space research." International Conference on Technology and Social Science 2019, Kiryu, Japan, May 8, 2019.

Abstract book. International Conference on Technology and Social Science 2019, Kiryu, Japan, May 8, 2019. , May-2019

Abstracts for Journals and Proceedings Chiu Y-J, Thomas TN, Choe LH, Lee KH, Fujiwara K. "The early response of cultured mammalian cells to changes in gravity: Increased actin dynamics." 2nd Mechanobiology Meeting in Vietnam, Quy Nhon, Vietnam, July 7-14, 2019.

Abstract book. 2nd Mechanobiology Meeting in Vietnam, Quy Nhon, Vietnam, July 7-14, 2019. , Jul-2019

Articles in Other Journals or Periodicals Takahashi A, Fujiwara K, Hada M. "Increased chromosome aberrations in cells exposed to simulated space environment with microgravity and radiation." The Cell. 2019 Feb;51(2):76-9. (in Japanese) , Feb-2019
Articles in Peer-reviewed Journals Ikeda H, Muratani M, Hidema J, Hada M, Fujiwara K, Souda H, Yoshida Y, Takahashi A. "Expression profile of cell cycle-related genes in human fibroblasts exposed simultaneously to radiation and simulated microgravity." Int J Mol Sci. 2019 Sep 26;20(19):E4791. https://doi.org/10.3390/ijms20194791 ; PubMed PMID: 31561588; PubMed Central PMCID: PMC6801845 , Sep-2019
Articles in Peer-reviewed Journals Hada M, Ikeda H, Rhone JR, Beitman AJ, Plante I, Souda H, Yoshida Y, Held KD, Fujiwara K, Saganti PB, Takahashi A. "Increased chromosome aberrations in cells exposed simultaneously to simulated microgravity and radiation." Int J Mol Sci. 2018 Dec 22;20(1):E43. https://doi.org/10.3390/ijms20010043 ; PubMed PMID: 30583489; PubMed Central PMCID: PMC6337712 , Dec-2018
Project Title:  Combined Effects of Simulated Microgravity and Space Radiation on Human Cells Reduce
Images: icon  Fiscal Year: FY 2019 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Cell & Molecular Biology   | Animal Biology: Vertebrate  
Start Date: 10/26/2018  
End Date: 10/25/2021  
Task Last Updated: 01/02/2019 
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Principal Investigator/Affiliation:   Hada, Megumi  Ph.D. / Prairie View A&M University 
Address:  College of Arts and Sciences, PO BOX 519, MS-2230, New Science Bldg 
 
Prairie View , TX 77446 
Email: mehada@pvamu.edu 
Phone: 936-261-3155  
Congressional District: 10 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Prairie View A&M University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Wang, Jing  Ph.D. University of Texas MD Anderson Cancer Center 
Takahashi, Akihisa  Ph.D. Gunma University Heavy Ion Medical Center, Japan 
Fujiwara, Keigi  Ph.D. University of Texas MD Anderson Cancer Center 
Project Information: Grant/Contract No. 80NSSC19K0133 
Responsible Center: NASA KSC 
Grant Monitor: Zhang, Ye  
Center Contact: 321-861-3253 
Ye.Zhang-1@nasa.gov 
Unique ID: 12118 
Solicitation / Funding Source: 2016-17 Space Biology (ROSBio) NNH16ZTT001N-FG. App G: Flight and Ground Space Biology Research 
Grant/Contract No.: 80NSSC19K0133 
Project Type: GROUND 
Flight Program:  
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Space Biology Element: (1) Cell & Molecular Biology
(2) Animal Biology: Vertebrate
Space Biology Cross-Element Discipline: None
Space Biology Special Category: (1) Cell Culture
(2) Translational (Countermeasure) Potential
Task Description: Space radiation and microgravity are two major environmental stressors for human in space travel. One of the fundamental questions in space biology research is whether the combined effects of microgravity and exposure to cosmic radiation are synergistic. While studies addressing this question have been carried out for half a century in space or using simulated microgravity on the ground, the reported results are conflicting. Although the reason for the variation in results is not known, it is possible that it may be due to the diversity of biological systems used but more importantly to the experimental designs and hardware used in these studies. For the assessment and management of human health risks in future Moon and Mars Missions, it is necessary to obtain more basic data on the molecular and cellular responses to combined effects of radiation and microgravity.

To establish a firm baseline database, we propose to undertake a systematic study on cultured mammalian cells' responses to the simultaneous insult of radiation and microgravity (both immediate and long term) to elucidate the molecular signaling pathways that lead to these biological effects. The results of the study will provide cellular and molecular biological bases for the assessment and management of human health risks in space.

Recently Dr. Takahashi, co-investigator of this proposal, has developed microgravity-irradiation systems consisting of a 3D clinostat synchronized to the carbon-ion or X-ray irradiation systems. Our new experimental setup allows us to avoid stopping clinostat rotation during irradiation, which was required in all other previous experiments. Gunma University Heavy Ion Medical Center is the only facility in the world where we can expose samples to high-linear energy transfer (LET) irradiation as well as low-LET irradiation under the simulated microgravity condition (i.e., without interrupting clinostat rotation).

Our preliminary data obtained from the use of this new device on gene expression in human fibroblasts show that splicing cycle-related genes and cell cycle related genes are significantly up-regulated and S-phase DNA replication and DNA repair-related genes were down-regulated with C-ion irradiation under simulated microgravity.

In this proposal we will investigate 3 different endpoints from early to late responses in 2 human cell lines using our new devices to study combined effects of microgravity and space radiation. Human fibroblasts and epithelial cells will be exposed to X-rays and C-ions under the simulated microgravity condition (rotated with 3-D clinostat). Control cells will be irradiated in 1G environment (with the static stage). We will investigate the extent of expression of specific proteins and of the post-translational modification states of signaling proteins (Aim 1), gene expressions and the pathways involved (Aim 2), and the extent of chromosome aberrations (Aim 3) caused by the combined effects of simulated microgravity and radiation. To investigate from the early to late endpoints in the same cell types will provide cellular and molecular biological data that are needed to understand the impact of combined effects of simulated microgravity and space radiation on human health. One of the selected endpoints is chromosome aberration, which is a well-established biomarker for cancer risk and has been used by NASA for the risk assessment of astronauts. Studying this endpoint allows us to compare our results to the astronauts' data after their International Space Station missions.

Completion of this proposal will allow us to determine how the combination of microgravity and radiation will affect the transcriptomic, metabolomic, and proteomic states of cells as well as heritable changes in DNA. These finding will allow us to help develop the countermeasures for the future space missions.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2019 
Task Progress: New project for FY2019.

Bibliography: Description: (Last Updated: 02/07/2024) 

Show Cumulative Bibliography
 
 None in FY 2019