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DNA methylation in kidney repair after ischemic AKI

Award Number: R01DK058831
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2001
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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DNA methylation in kidney repair after ischemic AKI - Acute kidney injury (AKI) is associated with high mortality and increasing prevalence. After AKI, some patients can fully recover but AKI is a risk factor for, and may progress to, chronic kidney disease (CKD). Kidney repair is a key determinant of the outcome or prognosis of AKI survivors. Especially, maladaptive kidney repair after severe or multiple episodes of AKI often leads to chronic renal pathologies characterized by tubular degeneration, chronic inflammation, interstitial fibrosis, and progressive decline of renal function. DNA methylation, catalyzed by DNA methyltransferase (DNMT), is a major epigenetic mechanism in health and disease. However, very few studies examined DNA methylation in AKI and post-AKI kidney repair. In preliminary studies, we demonstrated the induction of DNMT1 and DNMT3a along with DNA methylation during kidney repair. We further suggested the involvement of DNA methylation in maladaptive kidney repair by showing the effect of 5-aza-2'-deoxycytidine (5-aza), a pharmacological inhibitor of DNMT. In addition, our global DNA methylation assay has identified differential DNA methylation of multiple genes in post-IRI kidneys, among which homeobox A5 (Hoxa5) and microRNA-219 (miR-219) were hypermethylated at their gene promoters and the hypermethylation was associated with down-regulation of their expression. In this application, we hypothesize that: DNA methylation by DNMTs plays a critical role in maladaptive kidney repair after ischemic AKI. Specifically, hypermethylation of Hoxa5 and miR-219 leads to down-regulation of these genes, resulting in changes in downstream gene expression for the development of renal fibrosis. We propose three specific aims to: 1, test the hypothesis that DNA methylation by DNMTs plays a critical role in maladaptive kidney repair; 2, test the hypothesis that hypermethylation leads to the down-regulation of Hoxa5 in maladaptive kidney repair resulting in pro-fibrotic cell signaling for renal fibrosis; and 3, test the hypothesis that hypermethylation represses miR-219 in maladaptive kidney repair leading to pro-fibrosis gene expression. The work will gain significant new insights into epigenetic regulation of kidney repair. Moreover, by targeting DNA methylation, we may identify novel therapeutic strategies to improve kidney repair and the prognosis of AKI survivors.


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: 2026 ( Subtotal = $0 )
2026	2025	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	23	1/16/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $396,830 )
2025	2025	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	23	7/31/2025	NON-COMPETING CONTINUATION	$396,830
														Subtotal = $396,830

Issue Date FY: 2024 ( Subtotal = $380,956 )
2024	2024	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	22	8/22/2024	NON-COMPETING CONTINUATION	$380,956
2024	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	20	7/18/2024	COMPETING CONTINUATION	$509,684
2024	2021	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	19	7/18/2024	NON-COMPETING CONTINUATION	-$431,906
2024	2020	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	18	7/18/2024	NON-COMPETING CONTINUATION	-$77,778
														Subtotal = $380,956

Issue Date FY: 2023 ( Subtotal = $396,830 )
2023	2023	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	21	8/15/2023	NON-COMPETING CONTINUATION	$396,830
														Subtotal = $396,830

Issue Date FY: 2022 ( Subtotal = $396,830 )
2022	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	20	7/11/2022	COMPETING CONTINUATION	$396,830
														Subtotal = $396,830

Issue Date FY: 2021 ( Subtotal = $431,906 )
2021	2021	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	19	8/2/2021	NON-COMPETING CONTINUATION	$431,906
														Subtotal = $431,906

Issue Date FY: 2020 ( Subtotal = $431,906 )
2020	2020	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	18	9/15/2020	NON-COMPETING CONTINUATION	$431,906
														Subtotal = $431,906

Issue Date FY: 2019 ( Subtotal = $431,906 )
2019	2019	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	17	9/17/2019	NON-COMPETING CONTINUATION	$431,906
														Subtotal = $431,906

Issue Date FY: 2018 ( Subtotal = $431,906 )
2018	2018	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST # CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	16	9/6/2018	NON-COMPETING CONTINUATION	$431,906
2018	2017	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST # CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	15	1/18/2018	COMPETING CONTINUATION	$15,045
2018	2016	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST # CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	1/18/2018	EXTENSION WITH OR WITHOUT FUNDS	-$15,045
														Subtotal = $431,906

Issue Date FY: 2017 ( Subtotal = $431,906 )
2017	2017	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST # CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	15	1/26/2017	COMPETING CONTINUATION	$431,906
2017	2016	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST # CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	14	12/8/2016	EXTENSION WITH OR WITHOUT FUNDS	$11,530
2017	2016	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST # CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	14	8/14/2017	EXTENSION WITH OR WITHOUT FUNDS	$3,079
2017	2014	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST # CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	13	8/14/2017	NON-COMPETING CONTINUATION	-$3,079
2017	2014	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST # CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	12/8/2016	NON-COMPETING CONTINUATION	-$11,530
														Subtotal = $431,906

Issue Date FY: 2016 ( Subtotal = $326,250 )
2016	2016	GEORGIA REGENTS RESEARCH INSTITUTE INC	1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	14	8/3/2016	EXTENSION WITH OR WITHOUT FUNDS	$326,250
														Subtotal = $326,250

Issue Date FY: 2015 ( Subtotal = $0 )
2015	2014	GEORGIA REGENTS RESEARCH INSTITUTE INC	1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	9/11/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2014 ( Subtotal = $326,250 )
2014	2014	GEORGIA REGENTS RESEARCH INSTITUTE INC	1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	13	8/19/2014	NON-COMPETING CONTINUATION	$326,250
														Subtotal = $326,250

Issue Date FY: 2013 ( Subtotal = $314,832 )
2013	2013	GA HEALTH SCIENCE UNIVERSITY RESEARCH INSTITUTE, INC	1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	12	8/23/2013	NON-COMPETING CONTINUATION	$314,832
														Subtotal = $314,832

Issue Date FY: 2012 ( Subtotal = $326,250 )
2012	2012	MEDICAL COLLEGE OF GEORGIA, RESEARCH INSTITUTE	1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	11	8/22/2012	NON-COMPETING CONTINUATION	$326,250
														Subtotal = $326,250

Issue Date FY: 2011 ( Subtotal = $324,619 )
2011	2011	MEDICAL COLLEGE OF GEORGIA, RESEARCH INSTITUTE	1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	10	9/5/2011	COMPETING CONTINUATION	$324,619
2011	2009	MEDICAL COLLEGE OF GEORGIA, RESEARCH INSTITUTE	1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Trans-NIH Recovery Act Research Support	000	8	7/5/2011	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $324,619

Issue Date FY: 2010 ( Subtotal = $263,133 )
2010	2010	MEDICAL COLLEGE OF GEORGIA, RESEARCH INSTITUTE	1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	7/15/2010	NON-COMPETING CONTINUATION	$263,133
														Subtotal = $263,133

Issue Date FY: 2009 ( Subtotal = $290,487 )
2009	2009	MEDICAL COLLEGE OF GEORGIA, RESEARCH INSTITUTE	1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Trans-NIH Recovery Act Research Support	001	8	7/20/2009	SUPPLEMENT FOR EXPANSION	$24,696
2009	2009	MEDICAL COLLEGE OF GEORGIA, RESEARCH INSTITUTE	1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	6/17/2009	NON-COMPETING CONTINUATION	$265,791
														Subtotal = $290,487

Issue Date FY: 2008 ( Subtotal = $265,791 )
2008	2008	MEDICAL COLLEGE OF GEORGIA, RESEARCH INSTITUTE	RESEARCH INSTITUTE	AUGUSTA	GA	30912	RICHMOND	USA	Kidney Diseases, Urology and Hematology Research	000	7	7/10/2008	NON-COMPETING CONTINUATION	$265,791
														Subtotal = $265,791

Issue Date FY: 2007 ( Subtotal = $271,215 ) (Continued on the next page)
Grand Total All Awards = $7,515,178

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DNA methylation in kidney repair after ischemic AKI

Award Number: R01DK058831

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2001

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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