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Project Title:  A Determination of Bioactive Proteins Secreted by the Human Vasculature in Response to Low Dose Space Radiation Reduce
Images: icon  Fiscal Year: FY 2019 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 08/01/2018  
End Date: 07/31/2020  
Task Last Updated: 05/06/2020 
Download report in PDF pdf
Principal Investigator/Affiliation:   Grabham, Peter  Ph.D. / Columbia University 
Address:  Center for Radiological Research 
630W W 168th St, VC 11-243 
New York , NY 10032-3702 
Email: pwg2@cumc.columbia.edu 
Phone: 646-761-1275  
Congressional District: 13 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Columbia University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Brown, Lewis  Ph.D. Columbia University 
Project Information: Grant/Contract No. 80NSSC18K1492 
Responsible Center: NASA JSC 
Grant Monitor:  
Center Contact:   
Solicitation: 2017 HERO 80JSC017N0001-Crew Health and Performance (FLAGSHIP1, OMNIBUS). Appendix A-Flagship1, Appendix B-Omnibus 
Grant/Contract No.: 80NSSC18K1492 
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) Degen-IRP Rev J:Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure and Secondary Spaceflight Stressors (IRP Rev J)
Human Research Program Gaps: (1) Degen01:How can tissue specific experimental models be developed for the major degenerative tissue risks, including cardiovascular, lens, digestive, endocrine, and other tissue systems in order to estimate space radiation risks for degenerative diseases? (IRP Rev F)
(2) Degen02:What are the adverse outcome pathways associated with degenerative tissues changes in the cardiovascular, cerebrovascular, lens, immune, digestive, endocrine, and other tissue systems? What are the key events or hallmarks, their time sequence, and their associated biomarkers? (IRP Rev J)
Flight Assignment/Project Notes: NOTE: End date changed to 7/31/2020 per NSSC information (Ed., 1/29/2020)

Task Description: The specific purpose of the research proposed here is to determine the proteins that are potentially released into the blood stream by the lining of the human vasculature in response to exposure to space radiation. This would create a useful database for radiobiology studies and comparisons with the proteins secreted in astronaut blood. Such proteins have the potential to cause pathological processes such as inflammation, they are also spread around the body in the blood, and are important factors in many pathologies. The microvasculature permeates all tissues at the microscopic level so the whole body is a target for charged particles. A single heavy ion particle would be expected to traverse many microvessels as it passes through the body causing a more widespread response. Studies on the effect of different charged particles on human 3D microvessel models shows that both developing and mature microvessels lose structure and function after exposure to very low doses of various charged particles. Mature microvessels lose structure detectible as low as 1.25 cGy. Angiogenesis, the growth of new vessels, is inhibited by light ions and heavy ions detectible at 1.25 cGy. Even more striking, the combined effect of each ion has a synergistic effect detectible as low as 0.6 cGy. The low fluence of these doses indicates a bystander effect where the response is transmitted to other cells and such a mechanism would involve the secretion of molecules by the target cell. We propose to use proteomics and other techniques to determine the proteins secreted by the human microvessel models. A database of these proteins secreted by human tissue models would not only be of great use to a number of researchers investigating a diverse number of pathologies related to space radiation but also provide insights into the mechanisms of the vascular response to charged particles.

The specific purpose of the research proposed here is to determine the proteins that are potentially released into the blood stream by the lining of the human vasculature in response to exposure to space radiation. This would create a useful database for radiobiology studies and comparisons with the proteins secreted in astronaut blood. Such proteins have the potential to cause pathological processes such as inflammation, they are also spread around the body in the blood, and are important factors in many pathologies. The microvasculature permeates all tissues at the microscopic level so the whole body is a target for charged particles. A single heavy ion particle would be expected to traverse many microvessels as it passes through the body causing a more widespread response. Studies on the effect of different charged particles on human 3D microvessel models shows that both developing and mature microvessels lose structure and function after exposure to very low doses of various charged particles. Mature microvessels lose structure detectible as low as 1.25 cGy. Angiogenesis, the growth of new vessels, is inhibited by light ions and heavy ions detectible at 1.25 cGy. Even more striking, the combined effect of each ion has a synergistic effect detectible as low as 0.6 cGy. The low fluence of these doses indicates a bystander effect where the response is transmitted to other cells and such a mechanism would involve the secretion of molecules by the target cell. We propose to use proteomics and other techniques to determine the proteins secreted by the human microvessel models. A database of these proteins secreted by human tissue models would not only be of great use to a number of researchers investigating a diverse number of pathologies related to space radiation but also provide insights into the mechanisms of the vascular response to charged particles.

Amended Aims—November 2019

Additional aims were included for the determination of relative biological effectiveness (RBEs) for the 5 ion galactic cosmic radiation (GCR) simulations.

Aim 1. Create RBEs for the vascular damage endpoints.

Aim 1a Carry out Gamma radiation studies at Brookhaven National Laboratory (BNL) for the determination of reference RBEs.

Aim 1b Carry out charged particle studies at BNL for the determination of RBEs.

Aim 2. Identify the proteins secreted by the endothelial cells during angiogenesis and in mature human 3 D micro-vessel tissue models in response to radiation.

Aim 2a Development of the proteomics assay.

Aim 2b Identify the proteins secreted by the endothelial cells during angiogenesis and in mature human 3 D micro-vessel tissue models in response to gamma radiation.

Aim 2c Identify the proteins secreted by the endothelial cells during angiogenesis and in mature human 3 D micro-vessel tissue models in response to the Simplified GCR sim.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2019 
Task Progress: Note information below is from report submitted to Human Research Program November 2019.

1) By the summer of 2019 Aims 1a and b had been partially carried out for Mature vessels.

2) Aim 1a and 1b for developing microvessels (angiogenesis) were not yet completed. The new protocol requested by NASA that entails remaining at Brookhaven for an extra day does not appear to be compatible with microvessel growth. The reasons for this are unknown but we continued to trouble shoot the assay through the summer.

3) By the Fall run (19C – the last possible run for the current time limit) culture problems had been resolved. In the 2 visits for this run we have completed one dose response for angiogenesis in addition to proteomics samples and the samples are now being processed.

4) Work on the sample preparation for proteomics studies has been carried out and, as expected, a scale up of the cultures was necessary. A larger gel matrix proved to be less stable and detached from the flasks.

5) A goal of 5 samples for each condition (20 total) was set by the Proteomics expert CoInvestigator Dr. Brown. These goals were reached by the end of the Fall (19C) run. Samples will be processed and delivered to Dr. Brown.

Bibliography Type: Description: (Last Updated: 07/19/2017)  Show Cumulative Bibliography Listing
 
 None in FY 2019
Project Title:  A Determination of Bioactive Proteins Secreted by the Human Vasculature in Response to Low Dose Space Radiation Reduce
Images: icon  Fiscal Year: FY 2018 
Division: Human Research 
Research Discipline/Element:
HRP SR:Space Radiation
Start Date: 08/01/2018  
End Date: 07/31/2020  
Task Last Updated: 10/30/2018 
Download report in PDF pdf
Principal Investigator/Affiliation:   Grabham, Peter  Ph.D. / Columbia University 
Address:  Center for Radiological Research 
630W W 168th St, VC 11-243 
New York , NY 10032-3702 
Email: pwg2@cumc.columbia.edu 
Phone: 646-761-1275  
Congressional District: 13 
Web:  
Organization Type: UNIVERSITY 
Organization Name: Columbia University 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Brown, Lewis  Ph.D. Columbia University 
Project Information: Grant/Contract No. 80NSSC18K1492 
Responsible Center: NASA JSC 
Grant Monitor: Simonsen, Lisa  
Center Contact:  
lisa.c.simonsen@nasa.gov 
Solicitation: 2017 HERO 80JSC017N0001-Crew Health and Performance (FLAGSHIP1, OMNIBUS). Appendix A-Flagship1, Appendix B-Omnibus 
Grant/Contract No.: 80NSSC18K1492 
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) Degen-IRP Rev J:Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure and Secondary Spaceflight Stressors (IRP Rev J)
Human Research Program Gaps: (1) Degen01:How can tissue specific experimental models be developed for the major degenerative tissue risks, including cardiovascular, lens, digestive, endocrine, and other tissue systems in order to estimate space radiation risks for degenerative diseases? (IRP Rev F)
(2) Degen02:What are the adverse outcome pathways associated with degenerative tissues changes in the cardiovascular, cerebrovascular, lens, immune, digestive, endocrine, and other tissue systems? What are the key events or hallmarks, their time sequence, and their associated biomarkers? (IRP Rev J)
Flight Assignment/Project Notes: NOTE: End date changed to 7/31/2020 per NSSC information; original end date was 1/31/2020 (Ed., 1/29/2020)

Task Description: The specific purpose of the research proposed here is to determine the proteins that are potentially released into the blood stream by the lining of the human vasculature in response to exposure to space radiation. This would create a useful database for radiobiology studies and comparisons with the proteins secreted in astronaut blood. Such proteins have the potential to cause pathological processes such as inflammation, they are also spread around the body in the blood, and are important factors in many pathologies. The microvasculature permeates all tissues at the microscopic level so the whole body is a target for charged particles. A single heavy ion particle would be expected to traverse many microvessels as it passes through the body causing a more widespread response. Studies on the effect of different charged particles on human 3D microvessel models shows that both developing and mature microvessels lose structure and function after exposure to very low doses of various charged particles. Mature microvessels lose structure detectible as low as 1.25 cGy. Angiogenesis, the growth of new vessels, is inhibited by light ions and heavy ions detectible at 1.25 cGy. Even more striking, the combined effect of each ion has a synergistic effect detectible as low as 0.6 cGy. The low fluence of these doses indicates a bystander effect where the response is transmitted to other cells and such a mechanism would involve the secretion of molecules by the target cell. We propose to use proteomics and other techniques to determine the proteins secreted by the human microvessel models. A database of these proteins secreted by human tissue models would not only be of great use to a number of researchers investigating a diverse number of pathologies related to space radiation but also provide insights into the mechanisms of the vascular response to charged particles.

Research Impact/Earth Benefits:

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

Bibliography Type: Description: (Last Updated: 07/19/2017)  Show Cumulative Bibliography Listing
 
 None in FY 2018