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Project Title:  Predictive Biomarkers for Space Radiation Induced Cancer and Cardiovascular Injury Risk Assessment Reduce
Images: icon  Fiscal Year: FY 2023 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
 Start Date: 07/02/2018  
End Date: 12/31/2023  
Task Last Updated: 05/02/2023 		 Download report in PDF pdf
Principal Investigator/Affiliation:   Jacob, Naduparambil K Ph.D. / Ohio State University 
Address:  Department of Radiation Oncology 
410 W, 12th Ave, 351 Wiseman Hall 
Columbus , OH 43210 		 Email: naduparambil.jacob@osumc.edu 
Phone: 614-685-4246  
Congressional District: 3 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: Ohio State University 
Joint Agency:  
Comments:  
Key Personnel Changes / Previous PI: April 2021 report: Dr. Peter Lee is no longer CoInvestigator on the project.
Project Information: Grant/Contract No. 80NSSC18K1691 
Responsible Center: NASA JSC 
Grant Monitor: Elgart, Robin  
Center Contact: 281-244-0596 (o)/832-221-4576 (m) 
shona.elgart@nasa.gov 
Unique ID: 12054  		Solicitation / Funding Source: 2017 HERO 80JSC017N0001-Crew Health and Performance (FLAGSHIP1, OMNIBUS). Appendix A-Flagship1, Appendix B-Omnibus 
Grant/Contract No.: 80NSSC18K1691 
Project Type: GROUND 
Flight Program:  
TechPort: No  		No. of Post Docs: 0 
No. of PhD Candidates: 0 
No. of Master's Candidates: 0 
No. of Bachelor's Candidates: 0  		No. of PhD Degrees: 0 
No. of Master's Degrees: 0 
No. of Bachelor's Degrees: 0 
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cancer:Risk of Radiation Carcinogenesis
(2) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes
Human Research Program Gaps: (1) Cancer-303:Identify early surrogate biomarkers that correlate with cancer, pre-malignancy, or the hallmarks of cancer.
(2) CV-102:Determine whether space radiation induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease.
Flight Assignment/Project Notes: NOTE: End date changed to 12/31/2023 per NSSC information (Ed., 10/29/23)

NOTE: End date changed to 7/1/2023 per NSSC information (Ed., 4/3/23)

NOTE: End date changed to 7/1/2022 per NSSC information (Ed., 6/22/21)

NOTE: End date changed to 7/1/2021 per NSSC information (Ed., 9/25/20)

Task Description: To reduce the uncertainty in estimates of cancer and cardiovascular risks from space radiation, we will evaluate changes in molecular biomarkers in rodents and rabbits exposed to ions relevant to exposures of astronauts in the space environment. Serum, heart, liver, and lung tissues collected from exposed animals and matching controls (as available) will be used for biomarker discovery following systems-biology approaches. The study will use modern analytic technologies and rigorous statistics for assessing changes in expression of microRNAs (miRNAs) associated with clinical endpoints for mechanistic understanding of disease initiation and progression. Analysis of samples from patients receiving radiation therapy and organ targeted and organ protected low-linear energy transfer (LET) irradiation model studies have shown changes in circulating miRNAs originating from organ systems as a function of dose exposed and time. Circulating miRNAs collected from mice exposed to low doses of neutrons will be compared with gamma rays and sham controls of changes in cancer endpoints. Cellular and molecular mechanisms involved in space radiation-induced cardiovascular disease, and cancer will be studied, which will contribute to risk assessment and developing effective countermeasures.

Research Impact/Earth Benefits: The goal is to develop blood test for early detection of delayed cardiovascular complications and cancers resulting from high-LET radiation exposure to astronauts during long duration space travel.

Task Progress & Bibliography Information FY2023 
Task Progress: In the reporting period, lung and liver specimens collected from mice exposed to relevant doses of high-LET radiation were compared for the discovery of long non-coding RNAs (lncRNAs) as biomarkers and potential regulators of radiation carcinogenesis. Samples collected from NASA-sponsored animal studies were evaluated for lncRNAs in mice irradiated with various low doses (sham, 118mGy and 400mGy) of neutrons at chronic dose rates and euthanized ~800 days post-exposure for tissue sampling.

Bibliography: Description: (Last Updated: 06/02/2023) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Liu J, Yadav M, Jacob NK. " Identification of long non-coding RNA altered in lung after exposure to chronic low-dose space relevant radiation." NASA Human Research Program Investigators’ Workshop, February 2023.

Abstracts. NASA Human Research Program Investigators’ Workshop, Galveston, Texas, February 7-9, 2023. , Feb-2023

Articles in Peer-reviewed Journals Yadav M, Liu J, Song F, Mo X, Jacob NR, Xu-Welliver M, Chakravarti A, Jacob NK. "Utility of circulating microRNA-150 for rapid evaluation of bone marrow depletion after radiation, and efficiency of bone marrow reconstitution." Int J Radiat Oncol Biol Phys. 2022 Mar 15;112(4):964-974. https://doi.org/10.1016/j.ijrobp.2021.10.150 ; PubMed PMID: 34767935 , Mar-2022
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Project Title:  Predictive Biomarkers for Space Radiation Induced Cancer and Cardiovascular Injury Risk Assessment Reduce
Images: icon  Fiscal Year: FY 2022 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
 Start Date: 07/02/2018  
End Date: 07/01/2022  
Task Last Updated: 04/29/2022 		 Download report in PDF pdf
Principal Investigator/Affiliation:   Jacob, Naduparambil K Ph.D. / Ohio State University 
Address:  Department of Radiation Oncology 
410 W, 12th Ave, 351 Wiseman Hall 
Columbus , OH 43210 		 Email: naduparambil.jacob@osumc.edu 
Phone: 614-685-4246  
Congressional District: 3 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: Ohio State University 
Joint Agency:  
Comments:  
Key Personnel Changes / Previous PI: April 2021 report: Dr. Peter Lee is no longer CoInvestigator on the project.
Project Information: Grant/Contract No. 80NSSC18K1691 
Responsible Center: NASA JSC 
Grant Monitor: Elgart, Robin  
Center Contact: 281-244-0596 (o)/832-221-4576 (m) 
shona.elgart@nasa.gov 
Unique ID: 12054  		Solicitation / Funding Source: 2017 HERO 80JSC017N0001-Crew Health and Performance (FLAGSHIP1, OMNIBUS). Appendix A-Flagship1, Appendix B-Omnibus 
Grant/Contract No.: 80NSSC18K1691 
Project Type: GROUND 
Flight Program:  
TechPort: No  		No. of Post Docs: 0 
No. of PhD Candidates: 0 
No. of Master's Candidates: 0 
No. of Bachelor's Candidates: 0  		No. of PhD Degrees: 0 
No. of Master's Degrees: 0 
No. of Bachelor's Degrees: 0 
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cancer:Risk of Radiation Carcinogenesis
(2) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes
Human Research Program Gaps: (1) Cancer-303:Identify early surrogate biomarkers that correlate with cancer, pre-malignancy, or the hallmarks of cancer.
(2) CV-102:Determine whether space radiation induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease.
Flight Assignment/Project Notes: NOTE: End date changed to 7/1/2022 per NSSC information (Ed., 6/22/21)

NOTE: End date changed to 7/1/2021 per NSSC information (Ed., 9/25/20)

Task Description: To reduce the uncertainty in estimates of cancer and cardiovascular risks from space radiation, we will evaluate changes in molecular biomarkers in rodents and rabbits exposed to ions relevant to exposures of astronauts in the space environment. Serum, heart, liver, and lung tissues collected from exposed animals and matching controls (as available) will be used for biomarker discovery following systems-biology approaches. The study will use modern analytic technologies and rigorous statistics for assessing changes in expression of microRNAs (miRNAs) associated with clinical endpoints for mechanistic understanding of disease initiation and progression. Analysis of samples from patients receiving radiation therapy and organ targeted and organ protected low-linear energy transfer (LET) irradiation model studies have shown changes in circulating miRNAs originating from organ systems as a function of dose exposed and time. Circulating miRNAs collected from mice exposed to low doses of neutrons will be compared with gamma rays and sham controls of changes in cancer endpoints. Cellular and molecular mechanisms involved in space radiation-induced cardiovascular disease, and cancer will be studied, which will contribute to risk assessment and developing effective countermeasures.

Research Impact/Earth Benefits: The goal is to develop blood test for early detection of delayed cardiovascular complications and cancers resulting from high-LET radiation exposure to astronauts during long duration space travel.

Task Progress & Bibliography Information FY2022 
Task Progress: In the reporting year, we have processed and analyzed lung specimens collected from two strains of mice C3H and BALB/c. These mice were previously exposed to varying chronic low-dose neutrons (sham, 118 mGy, 200 mGy, or 400 mGy), maintained for >2 years for carcinogenesis risk assessment and sacrificed at around 800 days after exposure. We have completed the analysis of lung levels of 10 miRNAs in 139 mice. The candidates selected in the analyses include molecules that we have identified from our earlier screen for biomarkers (by nanoString based profiling) and/or mechanistically linked to potentially chronic alterations that are associated with later occurring carcinogenesis and degenerative diseases. The discovery and validation of functional biomarkers in multiple animal models are predicted to help us develop benchmarks for risk assessment.

Bibliography: Description: (Last Updated: 06/02/2023) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Yadav M, Joseph L, Jacob NK. "Candidate biomarkers for cancer risk assessment after exposure to space radiation. " 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

Articles in Peer-reviewed Journals Yadav M, Liu J, Song F, Mo X, Jacob NR, Xu-Welliver M, Chakravarti A, Jacob NK. "Utility of circulating MicroRNA-150 for rapid evaluation of bone marrow depletion after radiation and efficiency of bone marrow reconstitution. " Int J Radiat Oncol Biol Phys. 2022 Mar 15;112(4):964-74. https://doi.org/10.1016/j.ijrobp.2021.10.150 ; PubMed PMID: 34767935. , Mar-2022
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Project Title:  Predictive Biomarkers for Space Radiation Induced Cancer and Cardiovascular Injury Risk Assessment Reduce
Images: icon  Fiscal Year: FY 2021 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
 Start Date: 07/02/2018  
End Date: 07/01/2022  
Task Last Updated: 04/29/2021 		 Download report in PDF pdf
Principal Investigator/Affiliation:   Jacob, Naduparambil K Ph.D. / Ohio State University 
Address:  Department of Radiation Oncology 
410 W, 12th Ave, 351 Wiseman Hall 
Columbus , OH 43210 		 Email: naduparambil.jacob@osumc.edu 
Phone: 614-685-4246  
Congressional District: 3 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: Ohio State University 
Joint Agency:  
Comments:  
Key Personnel Changes / Previous PI: April 2021 report: Dr. Peter Lee is no longer CoInvestigator on the project.
Project Information: Grant/Contract No. 80NSSC18K1691 
Responsible Center: NASA JSC 
Grant Monitor: Elgart, Robin  
Center Contact: 281-244-0596 (o)/832-221-4576 (m) 
shona.elgart@nasa.gov 
Unique ID: 12054  		Solicitation / Funding Source: 2017 HERO 80JSC017N0001-Crew Health and Performance (FLAGSHIP1, OMNIBUS). Appendix A-Flagship1, Appendix B-Omnibus 
Grant/Contract No.: 80NSSC18K1691 
Project Type: GROUND 
Flight Program:  
TechPort: No  		No. of Post Docs: 0 
No. of PhD Candidates: 0 
No. of Master's Candidates: 0 
No. of Bachelor's Candidates: 0  		No. of PhD Degrees: 0 
No. of Master's Degrees: 0 
No. of Bachelor's Degrees: 0 
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cancer:Risk of Radiation Carcinogenesis
(2) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes
Human Research Program Gaps: (1) Cancer-303:Identify early surrogate biomarkers that correlate with cancer, pre-malignancy, or the hallmarks of cancer.
(2) CV-102:Determine whether space radiation induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease.
Flight Assignment/Project Notes: NOTE: End date changed to 7/1/2022 per NSSC information (Ed., 6/22/21)

NOTE: End date changed to 7/1/2021 per NSSC information (Ed., 9/25/20)

Task Description: To reduce the uncertainty in estimates of cancer and cardiovascular risks from space radiation, we will evaluate changes in molecular biomarkers in rodents and rabbits exposed to ions relevant to exposures of astronauts in the space environment. Serum, heart, liver, and lung tissues collected from exposed animals and matching controls (as available) will be used for biomarker discovery following systems-biology approaches. The study will use modern analytic technologies and rigorous statistics for assessing changes in expression of microRNAs (miRNAs) associated with clinical endpoints for mechanistic understanding of disease initiation and progression. Analysis of samples from patients receiving radiation therapy and organ targeted and organ protected low-linear energy transfer (LET) irradiation model studies have shown changes in circulating miRNAs originating from organ systems as a function of dose exposed and time. Circulating miRNAs collected from mice exposed to low doses of neutrons will be compared with gamma rays and sham controls of changes in cancer endpoints. Cellular and molecular mechanisms involved in space radiation-induced cardiovascular disease, and cancer will be studied, which will contribute to risk assessment and developing effective countermeasures.

Research Impact/Earth Benefits: The goal is to develop blood test for early detection of delayed cardiovascular complications and cancers resulting from high-LET radiation exposure to astronauts during long duration space travel.

Task Progress & Bibliography Information FY2021 
Task Progress: In the reporting year, we have analyzed serum specimens collected from C3H (male) and BALB/c (female) mice exposed to varying chronic low-dose rate neutrons and maintained for carcinogenesis risk assessment. These mice were previously exposed to chronic low-dose neutrons (sham, 118 mGy, 200 mGy, or 400 mGy) and sacrificed at around 800 days after exposure. We have completed the analysis of serum levels of 15 miRNAs in 139 mice, following an internally controlled assay that we have optimized for quantitative analysis of changes in circulating miRNAs. The candidates selected in the analyses include molecules that we have identified from our earlier screen for biomarkers (by nanoString based profiling) and/or are reported to be linked to molecular processes associated carcinogenesis and degenerative diseases. The discovery and validation of functional biomarkers in multiple animal models are predicted to help us develop benchmarks for both risk assessment and evaluation of efficacy of countermeasures.

Bibliography: Description: (Last Updated: 06/02/2023) 

Show Cumulative Bibliography
 
Significant Media Coverage Gourd E. "Potential new method for rapid diagnosis of radiation sickness. Commentary in Lancet Oncology on PI's work in article, Yadav M, Bhayana S, Liu J, Lu L, Huang J, Ma Y, Qamri Z, Mo X, Jacob DS, Parasa ST, Bhuiya N, Fadda P, Xu-Welliver M, Chakravarti A, Jacob NK. 'Two-miRNA-based finger-stick assay for estimation of absorbed ionizing radiation dose.' Sci Transl Med. 2020 Jul 15;12(552):eaaw5831. https://doi.org/10.1126/scitranslmed.aaw5831 [Ed note--see cumulative bibliography link] " Lancet Oncol. 2020 Sep;21(9):1142. https://doi.org/10.1016/S1470-2045(20)30421-6 ; PMID: 32738931; PMCID: PMC7392597, Sep-2020
Back to Search Results    
Project Title:  Predictive Biomarkers for Space Radiation Induced Cancer and Cardiovascular Injury Risk Assessment Reduce
Images: icon  Fiscal Year: FY 2020 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
 Start Date: 07/02/2018  
End Date: 07/01/2021  
Task Last Updated: 09/28/2020 		 Download report in PDF pdf
Principal Investigator/Affiliation:   Jacob, Naduparambil K Ph.D. / Ohio State University 
Address:  Department of Radiation Oncology 
410 W, 12th Ave, 351 Wiseman Hall 
Columbus , OH 43210 		 Email: naduparambil.jacob@osumc.edu 
Phone: 614-685-4246  
Congressional District: 3 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: Ohio State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Lee, Peter  M.D., Ph.D. Ohio State University 
Project Information: Grant/Contract No. 80NSSC18K1691 
Responsible Center: NASA JSC 
Grant Monitor: Elgart, Robin  
Center Contact: 281-244-0596 (o)/832-221-4576 (m) 
shona.elgart@nasa.gov 
Unique ID: 12054  		Solicitation / Funding Source: 2017 HERO 80JSC017N0001-Crew Health and Performance (FLAGSHIP1, OMNIBUS). Appendix A-Flagship1, Appendix B-Omnibus 
Grant/Contract No.: 80NSSC18K1691 
Project Type: GROUND 
Flight Program:  
TechPort: No  		No. of Post Docs: 0 
No. of PhD Candidates: 0 
No. of Master's Candidates: 0 
No. of Bachelor's Candidates: 0  		No. of PhD Degrees: 0 
No. of Master's Degrees: 0 
No. of Bachelor's Degrees: 0 
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cancer:Risk of Radiation Carcinogenesis
(2) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes
Human Research Program Gaps: (1) Cancer-303:Identify early surrogate biomarkers that correlate with cancer, pre-malignancy, or the hallmarks of cancer.
(2) CV-102:Determine whether space radiation induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease.
Flight Assignment/Project Notes: NOTE: End date changed to 7/1/2021 per NSSC information (Ed., 9/25/20)

Task Description: To reduce the uncertainty in estimates of cancer and cardiovascular risks from space radiation, we will evaluate changes in molecular biomarkers in rodents and rabbits exposed to ions relevant to exposures of astronauts in the space environment. Serum, heart, liver, and lung tissues collected from exposed animals and matching controls will be used for biomarker discovery following systems-biology approaches. The study will use modern analytic technologies and rigorous statistics for assessing changes in expression of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) associated with clinical endpoints for mechanistic understanding of disease initiation and progression. Analysis of samples from patients receiving radiation therapy and organ targeted and organ protected low-linear energy transfer (LET) irradiation model studies have shown changes in circulating miRNAs originating from organ systems as a function of dose and time, correlating with disease states. Archived cardiac specimens from rabbits and rats previously exposed to 0.5 Gy Proton or Oxygen ions with respective sham controls will be used for discovery and validation of space radiation-induced cardiovascular diseases. Changes in miRNAs mechanistically connected to inflammation and pathological changes using clinical, imaging, and biochemical endpoints of cardiovascular diseases will be evaluated. miRNAs and lncRNAs in lung, liver, and serum collected from mice exposed to low doses of neutrons ions will be compared with gamma rays and sham controls of changes in cancer endpoints. The availability of specimens from on-going or completed Carcinogenesis NASA Specialized Center of Research (NSCOR) and National Space Biomedical Research Institute (NSBRI) for Space Radiation Research studies focusing on cardiovascular diseases are ensured. Our project is cost-effective and unique because we will use samples both for developing cancer and cardiovascular risk assessment. Cellular and molecular mechanisms involved in space radiation-induced cardiovascular disease, lung, and liver cancer will be studied, which will significantly contribute to the testing of and validating effective countermeasures.

Research Impact/Earth Benefits: The goal is to develop blood test for early detection of delayed cardiovascular complications and cancers resulting from high-LET radiation exposure to astronauts during long duration space travel.

Task Progress & Bibliography Information FY2020 
Task Progress: To identify molecular biomarkers that have potential to provide early readout of delayed and late effects, specimens available through tissue sharing program were evaluated for changes in the expression of microRNAs. For discovery of microRNA biomarkers that are altered as a function of time after exposure to space radiation, an unbiased amplification-free hybridization based direct digital counting method (nanoString Counter profiling) was used. Robustness of the responses of candidate biomarkers identified from nanoString profiling is being validated by quantitative real-time PCR based approaches. The discovery and validation of biomarkers in multiple animal models is expected to help risk assessment and evaluation of the efficacy of countermeasures.

Bibliography: Description: (Last Updated: 06/02/2023) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Jacob N, Liu J, Yadav M, Bhayana S, Sridharan V, Boerma M. "microRNAs as radiation biododosimeters and early predictors of late effects." Abstract of a talk presented at 2020 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 27-30, 2020.

Abstract No. 20540. 2020 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 27-30, 2020. , Jan-2020

Articles in Peer-reviewed Journals Yadav M, Bhayana S, Liu J, Lu L, Huang J, Ma Y, Qamri Z, Mo X, Jacob DS, Parasa ST, Bhuiya N, Fadda P, Xu-Welliver M, Chakravarti A, Jacob NK. "Two-miRNA-based finger-stick assay for estimation of absorbed ionizing radiation dose." Sci Transl Med. 2020 Jul 15;12(552):eaaw5831. https://doi.org/10.1126/scitranslmed.aaw5831 ; PMID: 32669422 , Jul-2020
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Project Title:  Predictive Biomarkers for Space Radiation Induced Cancer and Cardiovascular Injury Risk Assessment Reduce
Images: icon  Fiscal Year: FY 2019 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
 Start Date: 07/02/2018  
End Date: 07/01/2020  
Task Last Updated: 04/26/2019 		 Download report in PDF pdf
Principal Investigator/Affiliation:   Jacob, Naduparambil K Ph.D. / Ohio State University 
Address:  Department of Radiation Oncology 
410 W, 12th Ave, 351 Wiseman Hall 
Columbus , OH 43210 		 Email: naduparambil.jacob@osumc.edu 
Phone: 614-685-4246  
Congressional District: 3 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: Ohio State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Lee, Peter  M.D., Ph.D. Ohio State University 
Project Information: Grant/Contract No. 80NSSC18K1691 
Responsible Center: NASA JSC 
Grant Monitor: Simonsen, Lisa  
Center Contact:  
lisa.c.simonsen@nasa.gov 
Unique ID: 12054  		Solicitation / Funding Source: 2017 HERO 80JSC017N0001-Crew Health and Performance (FLAGSHIP1, OMNIBUS). Appendix A-Flagship1, Appendix B-Omnibus 
Grant/Contract No.: 80NSSC18K1691 
Project Type: GROUND 
Flight Program:  
TechPort: No  		No. of Post Docs: 0 
No. of PhD Candidates: 0 
No. of Master's Candidates: 0 
No. of Bachelor's Candidates: 0  		No. of PhD Degrees: 0 
No. of Master's Degrees: 0 
No. of Bachelor's Degrees: 0 
Human Research Program Elements: (1) SR:Space Radiation
Human Research Program Risks: (1) Cancer:Risk of Radiation Carcinogenesis
(2) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes
Human Research Program Gaps: (1) Cancer-303:Identify early surrogate biomarkers that correlate with cancer, pre-malignancy, or the hallmarks of cancer.
(2) CV-102:Determine whether space radiation induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease.
Task Description: To reduce the uncertainty in estimates of cancer and cardiovascular risks from space radiation, we will evaluate changes in molecular biomarkers in rodents and rabbits exposed to ions relevant to exposures of astronauts in the space environment. Serum, heart, liver, and lung tissues collected from exposed animals and matching controls will be used for biomarker discovery following systems-biology approaches. The study will use modern analytic technologies and rigorous statistics for assessing changes in expression of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) associated with clinical endpoints for mechanistic understanding of disease initiation and progression. Analysis of samples from patients receiving radiation therapy and organ targeted and organ protected low-linear energy transfer (LET) irradiation model studies have shown changes in circulating miRNAs originating from organ systems as a function of dose and time, correlating with disease states. Archived cardiac specimens from rabbits and rats previously exposed to 0.5 Gy Proton or Oxygen ions with respective sham controls will be used for discovery and validation of space radiation-induced cardiovascular diseases. Changes in miRNAs mechanistically connected to inflammation and pathological changes using clinical, imaging, and biochemical endpoints of cardiovascular diseases will be evaluated. miRNAs and lncRNAs in lung, liver, and serum collected from mice exposed to 0.2 Gy Silicon ions will be compared with sham controls of changes in cancer endpoints. The availability of specimens (archived or upcoming sacrifices) from on-going or completed Carcinogenesis NASA Specialized Center of Research (NSCOR) and National Space Biomedical Research Institute (NSBRI) for Space Radiation Research studies focusing on cardiovascular diseases are ensured. Our project is cost-effective and unique because we will use samples both for developing cancer and cardiovascular risk assessment. Cellular and molecular mechanisms involved in space radiation-induced cardiovascular disease, lung, and liver cancer will be studied, which will significantly contribute to the testing of and validating effective countermeasures.

Research Impact/Earth Benefits: The goal is to develop blood test for early detection of delayed cardiovascular complications resulting from high-LET radiation exposure to astronauts during long duration space travel.

Task Progress & Bibliography Information FY2019 
Task Progress: Longer space mission results in an unavoidable exposure of space radiation to astronauts that may create potential health risks including late occurring cardiovascular diseases and cancers. In order to identify biomarkers with potential to provide early readout of cardiovascular injury and risk assessment, specimens available thorough tissue sharing program were evaluated for changes in the expression of microRNAs.

We hypothesized that space radiation-dependent DNA damage response and chronic inflammation will result in alteration of evolutionarily and functionally conserved microRNAs and as a readout of genetic/epigenetic reprogramming associated with initiation and progression of diseases. In the first year of the award, we focused on qualitative and quantitative analysis of microRNAs in cardiac tissue collected one year after the exposure of male Long Evans rats and New Zealand White rabbits to a single dose of 0.5 Gy proton (250 MeV) or 0.5 Gy oxygen ions (600 MeV/n).

For discovery of biomarkers that are altered as a function of time after exposure to space radiation: An unbiased amplification-free hybridization based direct digital counting method was used for profiling, which allowed the evaluation of relative changes in up to 800 miRNAs. Robustness of the responses of candidate biomarkers identified from nanoString profiling was validated by a quantitative real-time PCR based approaches. Moreover, some of the responding molecules identified are known to modulate chronic inflammation and progressive diseases providing a potential link to molecular processes associated with delayed fibrosis and hypertrophy. The discovery and validation of biomarkers conserved in multiple animal models are predicted to help develop benchmarks for both risk assessment and evaluation of efficacy of countermeasures.

Bibliography: Description: (Last Updated: 06/02/2023) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Jacob N, Liu J, Bhayana S, Yadav M, Lee P, Boerma M, Sridharan V. "MicroRNA Biomarkers of Radiation-induced Cardiovascular Injury." Radiation Health Effects. 2019 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2019.

2019 NASA Human Research Program Investigators’ Workshop, Galveston, TX, January 22-25, 2019. Poster #19193. , Jan-2019

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Project Title:  Predictive Biomarkers for Space Radiation Induced Cancer and Cardiovascular Injury Risk Assessment Reduce
Images: icon  Fiscal Year: FY 2018 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
 Start Date: 07/02/2018  
End Date: 07/01/2020  
Task Last Updated: 10/30/2018 		 Download report in PDF pdf
Principal Investigator/Affiliation:   Jacob, Naduparambil K Ph.D. / Ohio State University 
Address:  Department of Radiation Oncology 
410 W, 12th Ave, 351 Wiseman Hall 
Columbus , OH 43210 		 Email: naduparambil.jacob@osumc.edu 
Phone: 614-685-4246  
Congressional District: 3 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: Ohio State University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Lee, Peter  M.D., Ph.D. Ohio State University 
Project Information: Grant/Contract No. 80NSSC18K1691 
Responsible Center: NASA JSC 
Grant Monitor: Simonsen, Lisa  
Center Contact:  
lisa.c.simonsen@nasa.gov 
Unique ID: 12054  		Solicitation / Funding Source: 2017 HERO 80JSC017N0001-Crew Health and Performance (FLAGSHIP1, OMNIBUS). Appendix A-Flagship1, Appendix B-Omnibus 
Grant/Contract No.: 80NSSC18K1691 
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) SR:Space Radiation
Human Research Program Risks: (1) Cancer:Risk of Radiation Carcinogenesis
(2) Cardiovascular:Risk of Cardiovascular Adaptations Contributing to Adverse Mission Performance and Health Outcomes
Human Research Program Gaps: (1) Cancer-303:Identify early surrogate biomarkers that correlate with cancer, pre-malignancy, or the hallmarks of cancer.
(2) CV-102:Determine whether space radiation induces cardiovascular structural and functional changes and/or oxidative stress & damage (OSaD)/inflammation, that can contribute to development of disease.
Task Description: To reduce the uncertainty in estimates of cancer and cardiovascular risks from space radiation, we will evaluate changes in molecular biomarkers in rodents and rabbits exposed to ions relevant to exposures of astronauts in the space environment. Serum, heart, liver, and lung tissues collected from exposed animals and matching controls will be used for biomarker discovery following systems-biology approaches. The study will use modern analytic technologies and rigorous statistics for assessing changes in expression of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) associated with clinical endpoints for mechanistic understanding of disease initiation and progression. Analysis of samples from patients receiving radiation therapy and organ targeted and organ protected low-linear energy transfer (LET) irradiation model studies have shown changes in circulating miRNAs originating from organ systems as a function of dose and time, correlating with disease states. Archived cardiac specimens from rabbits and rats previously exposed to 0.5 Gy Proton or Oxygen ions with respective sham controls will be used for discovery and validation of space radiation-induced cardiovascular diseases. Changes in miRNAs mechanistically connected to inflammation and pathological changes using clinical, imaging, and biochemical endpoints of cardiovascular diseases will be evaluated. miRNAs and lncRNAs in lung, liver, and serum collected from mice exposed to 0.2 Gy Silicon ions will be compared with sham controls of changes in cancer endpoints. The availability of specimens (archived or upcoming sacrifices) from on-going or completed Carcinogenesis NASA Specialized Center of Research (NSCOR) and National Space Biomedical Research Institute (NSBRI) for Space Radiation Research studies focusing on cardiovascular diseases are ensured. Our project is cost-effective and unique because we will use samples both for developing cancer and cardiovascular risk assessment. Cellular and molecular mechanisms involved in space radiation-induced cardiovascular disease, lung, and liver cancer will be studied, which will significantly contribute to the testing of and validating effective countermeasures.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2018 
Task Progress: New project for FY2018.

Bibliography: Description: (Last Updated: 06/02/2023) 

Show Cumulative Bibliography
 
 None in FY 2018
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