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Genetics of epigenetic response to high circulating glucocorticoids and organophosphorus compounds

Award Number: R01ES031656
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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The USA sent approximately 700,000 troops to the Persian Gulf to participate in the 1990-91 Gulf War. Of those who returned, 25-30% complained of a generalized malaise with gastrointestinal, endocrinological, respiratory and neurological complaints, which was named Gulf War Illness (GWI). Many of those returning with GWI are still sick nearly 30 years after their exposure, with no cure. What changes allow these symptoms to persist over many years? Genetic variation among the troops may have caused them to respond differently to the exposure. Epigenetic alterations in gene regulation are the most likely candidate for the persistence of symptoms. We and others have developed an exposure regime in mice that mimics both troop exposures and biological effects of GWI. This model uses corticosterone pretreatment (CORT; to simulate physiological stress) combined with an irreversible acetylcholinesterase inhibitor, diisopropyl fluorophosphate (DFP); as troops were exposed to many acetylcholinesterase inhibitors. Initial studies showed acute changes in proinflammatory cytokine genes and changes in methylation of genes following exposure to CORT combined with DFP. PI Jones and colleagues have seen significant differences in proinflammatory gene expression response to the treatment among more than 25 different genotypes (i.e., inbred mouse strains) and have been able to map quantitative trait loci which mediate this effect. The proposed research takes the next step to understand the genetics of epigenetic changes related to the persistence of GWI.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $580,839 )
2024	2024	UNIVERSITY OF TENNESSEE	62 S DUNLAP ST	MEMPHIS	TN	38103	SHELBY	USA	Environmental Health	000	4	1/12/2024	NON-COMPETING CONTINUATION	$580,839
														Subtotal = $580,839

Issue Date FY: 2023 ( Subtotal = $580,839 )
2023	2023	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Environmental Health	000	3	1/26/2023	NON-COMPETING CONTINUATION	$580,839
														Subtotal = $580,839

Issue Date FY: 2022 ( Subtotal = $580,839 )
2022	2022	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Environmental Health	000	2	1/21/2022	NON-COMPETING CONTINUATION	$580,839
														Subtotal = $580,839

Issue Date FY: 2021 ( Subtotal = $580,839 )
2021	2021	UNIVERSITY OF TENNESSEE	62 S DUNLAP STREET STE 103	MEMPHIS	TN	38103	SHELBY	USA	Environmental Health	000	1	3/29/2021	NEW	$580,839
														Subtotal = $580,839

Grand Total All Awards = $2,323,356

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Genetics of epigenetic response to high circulating glucocorticoids and organophosphorus compounds

Award Number: R01ES031656

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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