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Project Title:  Identification of Functional Metabolomic Profiles Contributing to Physiological Adaptations to Simulated Spaceflight Reduce
Fiscal Year: FY 2020 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/18/2016  
End Date: 03/15/2020  
Task Last Updated: 07/15/2020 
Download report in PDF pdf
Principal Investigator/Affiliation:   Rana, Brinda  Ph.D. / University of California, San Diego 
Address:  Psychiatry 
9500 Gilman Dr, MC-0738 
La Jolla , CA 92093-5004 
Email: bkrana@ucsd.edu 
Phone: 858-822-4010  
Congressional District: 49 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of California, San Diego 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Fiehn, Oliver  Ph.D. University of California, Davis 
Lee, Stuart  Ph.D. KBR/NASA Johnson Space Center 
Macias, Brandon  Ph.D. University of California, San Diego 
Patel, Hemal  Ph.D. University of California, San Diego 
Sharma, Kumar  M.D. University of California, San Diego 
Smith, Scott  Ph.D. NASA Johnson Space Center 
Stenger, Michael  Ph.D. NASA Johnson Space Center 
Project Information: Grant/Contract No. NNX17AB12G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2015-16 HERO NNJ15ZSA001N-Crew Health (FLAGSHIP, NSBRI, OMNIBUS). Appendix A-Crew Health, Appendix B-NSBRI, Appendix C-Omnibus 
Grant/Contract No.: NNX17AB12G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:
No. of PhD Candidates:
No. of Master's Candidates:
No. of Bachelor's Candidates:
No. of PhD Degrees:
No. of Master's Degrees:
No. of Bachelor's Degrees:
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Muscle:Risk of Impaired Performance Due to Reduced Muscle Mass, Strength and Endurance
(2) OI:Risk of Orthostatic Intolerance during Re-Exposure to Gravity
Human Research Program Gaps: (1) CV03:Is orthostatic intolerance a potential hazard?
(2) M07:Develop the most efficient exercise program for maintenance of muscle fitness (IRP Rev F)
(3) M14:Indentify adjuncts to exercise countermeasures that can be used to better mitigate muscle loss (IRP Rev F)
Flight Assignment/Project Notes: NOTE: End date changed to 3/15/2020 per NSSC information (Ed., 4/6/2020)

Task Description: This study was designed to identify plasma and urine biomarkers that can be used to improve risk prediction for physiological manifestations due to simulated spaceflight (head down tilt bed rest) beyond current clinical measures and predictors. To accomplish this goal, we conducted untargeted and targeted metabolomic assays on archived 24 hour-pooled urine and plasma samples collected longitudinally for the 70 day head down tilt bed rest (HDTBR) study at the University of Texas Medical Branch between June 2011 and May 2014. The samples were obtained from 11 bed rest CONTROL subjects, 10 subjects in the EXERCISE arm of the study, and 8 subjects from the COMBINED EXERCISE AND TESTOSTERONE arm.

Research Impact/Earth Benefits: The bed rest model allows us to investigate the molecular mechanisms by which physical inactivity leads to the development of Earth based chronic diseases such as type 2 diabetes mellitus, obesity, and cardiovascular disorders. It can also guide us in the mechanisms by which reduced activity with aging or illness can lead to bone and muscle deconditioning.

Task Progress & Bibliography Information FY2020 
Task Progress: This study was designed to identify molecules in the plasma and urine that are altered in response to a simulated space environment, the head down tilt bed rest (HDTBR). The goal was to identify biomarkers that may be used to predict risk for the physiological manifestations of simulated spaceflight beyond current clinical measures and predictors.

To accomplish this goal, we conducted untargeted and targeted metabolomic assays on archived 24 hour-pooled urine and plasma samples collected longitudinally for the 70 day HDTBR study at the University of Texas Medical Branch between June 2011 and May 2014. The samples were obtained from 11 bed rest CONTROL subjects, 10 subjects in the EXERCISE arm of the study, and 8 subjects from the COMBINED EXERCISE AND TESTOSTERONE arm.

We applied untargeted metabolomics assays on plasma samples at 10- and 3-days pre-bed rest, day 28 of bed rest, return of normal position day 0, and post bed rest day 5 to measure metabolites related to primary metabolism, biogenic amines, and complex lipids. Due to our recent findings of spaceflight related changes in urine proteins, we extended our aims to also apply MS based proteomics on the urine samples at 9 days pre-bed rest, days 29 and 70 of bed rest, and 70 days post-bed rest to identify proteins that are altered in response to HDTBR.

We identified metabolic pathways related to mitochondrial function that are altered during bed rest. We also identified metabolic pathways that differentiate by study arm. By comparing the results of the present study with metabolomics data from the VaPER study which was done in parallel, we were able to identify metabolic responses that are related to specific factors of simulated spaceflight such as elevated CO2 and physical activity.

Bibliography Type: Description: (Last Updated: 07/30/2019) 

Show Cumulative Bibliography Listing
 
 None in FY 2020
Project Title:  Identification of Functional Metabolomic Profiles Contributing to Physiological Adaptations to Simulated Spaceflight Reduce
Fiscal Year: FY 2017 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 10/18/2016  
End Date: 12/16/2019  
Task Last Updated: 07/30/2019 
Download report in PDF pdf
Principal Investigator/Affiliation:   Rana, Brinda  Ph.D. / University of California, San Diego 
Address:  Psychiatry 
9500 Gilman Dr, MC-0738 
La Jolla , CA 92093-5004 
Email: bkrana@ucsd.edu 
Phone: 858-822-4010  
Congressional District: 49 
Web:  
Organization Type: UNIVERSITY 
Organization Name: University of California, San Diego 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Fiehn, Oliver  Ph.D. University of California, Davis 
Lee, Stuart  Ph.D. Wyle Laboratories, Inc./NASA Johnson Space Center 
Macias, Brandon  Ph.D. University of California, San Diego 
Patel, Hemal  Ph.D. University of California, San Diego 
Saito, Rintaro  Ph.D. University of California, San Diego 
Sharma, Kumar  M.D. University of California, San Diego 
Smith, Scott  Ph.D. NASA Johnson Space Center 
Stenger, Michael  Ph.D. Wyle Laboratories, Inc./NASA Johnson Space Center 
Project Information: Grant/Contract No. NNX17AB12G 
Responsible Center: NASA JSC 
Grant Monitor: Norsk, Peter  
Center Contact:  
Peter.norsk@nasa.gov 
Solicitation / Funding Source: 2015-16 HERO NNJ15ZSA001N-Crew Health (FLAGSHIP, NSBRI, OMNIBUS). Appendix A-Crew Health, Appendix B-NSBRI, Appendix C-Omnibus 
Grant/Contract No.: NNX17AB12G 
Project Type: GROUND 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) Muscle:Risk of Impaired Performance Due to Reduced Muscle Mass, Strength and Endurance
(2) OI:Risk of Orthostatic Intolerance during Re-Exposure to Gravity
Human Research Program Gaps: (1) CV03:Is orthostatic intolerance a potential hazard?
(2) M07:Develop the most efficient exercise program for maintenance of muscle fitness (IRP Rev F)
(3) M14:Indentify adjuncts to exercise countermeasures that can be used to better mitigate muscle loss (IRP Rev F)
Task Description: This study is designed to identify novel metabolomic biomarkers in serum and urine to detect and monitor the progression of physiological disturbances due to bed rest and to evaluate the effectiveness of countermeasures (exercise or exercise with testosterone treatment). Bed rest is a well-accepted model of space flight (simulating microgravity) that allows for the study of a larger number of subjects than is available in space flight, and thus is well-suited for more rapid evaluation of countermeasures and identification of potential biomarkers associated with deconditioning and countermeasure efficacy. Our study will focus on three physiological manifestations that are prevalent in crew members on long duration space flight and are also observed in bed rest studies and are the target of countermeasures: (1) altered cardiovascular function and potential sub-clinical manifestations of cardiovascular disease; (2) bone loss and increased fracture risk; and (3) muscle atrophy and decreased muscle strength. The overall goal of the proposed study is to identify serum and urine biomarkers that can be used to improve risk prediction for physiological manifestations due to bed rest beyond current clinical measures and known predictors.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2017 
Task Progress: New project for FY2017.

[EDITOR's NOTE: added to Task Book when identified in July 2019.]

Bibliography Type: Description: (Last Updated: 07/30/2019) 

Show Cumulative Bibliography Listing
 
 None in FY 2017