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The role of neutral ceramidase in acute kidney injury and its progression to chronic kidney disease.

Award Number: R01DK124112
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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The role of neutral ceramidase in acute kidney injury and its progression to chronic kidney disease. - Summary: The long-term goal of this proposal is to develop novel therapeutics for a serious unmet medical need, namely acute kidney injury (AKI) and its progression to chronic kidney disease (CKD) for which there are no treatments other than supportive care. The mechanisms of kidney injury and its progression to CKD are largely unknown and this proposal aims to fill some of these knowledge gaps. The short-term goal of this proposal is to validate a novel target for treating AKI and its progression to CKD for future drug development. This target is neutral ceramidase (NCD), an enzyme involved in metabolism of the sphingolipid ceramide. The proposal is based on a strong foundation of supporting preliminary data that indicates that mice lacking NCD are protected in models of AKI and CKD and in vitro data indicating that deletion or inhibition of NCD increases autophagy and protects cells from a variety of cellular stresses. Thus, this proposal will test the hypothesis that deletion or inhibition of NCD confers protection from AKI and injury-induced CKD via upregulation of autophagy. We will test this hypothesis with three interrelated but independent specific aims that will (1) determine the mechanism of protection of kidney cells in vitro from cellular stress when NCD is deleted or inhibited; (2) determine the role of NCD in AKI; and (3) determine the role of NCD in kidney injury progression to CKD. Data obtained in this proposal will provide many scientific and translational advances that are essential for achieving our long-term goal of developing therapeutics for this unmet medical need.


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: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	5/6/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $503,160 )
2023	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	1/20/2023	NON-COMPETING CONTINUATION	$503,160
														Subtotal = $503,160

Issue Date FY: 2022 ( Subtotal = $502,362 )
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	3/31/2022	NON-COMPETING CONTINUATION	$50,237
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/17/2021	NON-COMPETING CONTINUATION	$452,125
														Subtotal = $502,362

Issue Date FY: 2021 ( Subtotal = $501,565 )
2021	2021	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/17/2020	NON-COMPETING CONTINUATION	$451,408
2021	2021	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	2/2/2021	NON-COMPETING CONTINUATION	$50,157
														Subtotal = $501,565

Issue Date FY: 2020 ( Subtotal = $554,065 )
2020	2020	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/10/2020	NEW	$501,565
2020	2020	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	9/11/2020	SUPPLEMENT FOR EXPANSION	$52,500
														Subtotal = $554,065

Grand Total All Awards = $2,061,152

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The role of neutral ceramidase in acute kidney injury and its progression to chronic kidney disease.

Award Number: R01DK124112

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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