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Dual Oxidase 2 as a New Target for Treatment of Diabetic Nephropathy

Award Number: SC2GM136569
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/19/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Dual Oxidase 2 as a New Target for Treatment of Diabetic Nephropathy - Project Summary/Abstract Glomerular epithelial cell/podocyte injury is a prominent pathological feature of diabetic nephropathy (DN). In podocytes, hyperglycemia causes alteration of slit diaphragm proteins, foot process effacement, apoptosis and cell detachment, events that ultimately results in loss of renal function. High glucose concentrations (HG) and oxidative stress are potential mediators of glomerular injury in diabetes. We have evidence that Dual oxidase 2 (Duox2) is expressed in glomerular cells and contributes to HG-induced reactive oxygen species (ROS) generation as well as podocyte injury. Additionally, we have demonstrated that glomeruli isolated from DuoxA-/- mice were protected from high glucose-induced hydrogen peroxide generation. The central hypothesis of this proposal is that the ROS generated by Duox2 play a pivotal role in glomerular lesions and podocyte injury in the diabetic kidney. The goals of this proposal are to utilize in vitro and in vivo approaches to establish the importance of Duox2 in podocyte injury in the diabetic environment and identify the factors that are modulating Duox2 activity/expression. The role of Duox activators (DuoxA), translational mechanisms, and calcium in Duox2 activation will be explored. For the in vivo studies, we will utilize previously collected kidney cortices from diabetic and non-diabetic mice where DuoxA function is impaired. As no data related to Duox enzyme expression and function within podocytes are available, the experiments proposed should serve as proof of concept to demonstrate the utility of targeting the Duox/DuoxA system to reduce diabetes-mediated glomerular lesions. Characterization of the deleterious actions of Duox2 and identification of its regulators will contribute to the design of novel therapeutic interventions and will help establish adjunct therapy to treat DN. The studies will stress the relevance of the development of modulators of Duox2 expression and activity in the kidney as therapeutic agents to prevent or reverse DN. Furthermore, this proposal will enhance the research and educational infrastructure at the University of the Incarnate Word, introducing biomedical research experiences to underrepresented minority students who would otherwise lack such opportunities.


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 = $135,541 )
2024	2024	UNIVERSITY OF THE INCARNATE WORD	4301 BROADWAY	SAN ANTONIO	TX	78209	BEXAR	USA	Biomedical Research and Research Training	001	3	6/18/2024	NON-COMPETING CONTINUATION	$13,554
2024	2024	UNIVERSITY OF THE INCARNATE WORD	4301 BROADWAY	SAN ANTONIO	TX	78209	BEXAR	USA	Biomedical Research and Research Training	000	3	3/22/2024	NON-COMPETING CONTINUATION	$121,987
														Subtotal = $135,541

Issue Date FY: 2023 ( Subtotal = $139,443 )
2023	2023	UNIVERSITY OF THE INCARNATE WORD	4301 BROADWAY	SAN ANTONIO	TX	78209	BEXAR	USA	Biomedical Research and Research Training	001	2	6/13/2023	NON-COMPETING CONTINUATION	$135,541
2023	2022	UNIVERSITY OF THE INCARNATE WORD	4301 BROADWAY	SAN ANTONIO	TX	78209	BEXAR	USA	Biomedical Research and Research Training	000	1	5/23/2023	NEW	$3,902
														Subtotal = $139,443

Issue Date FY: 2022 ( Subtotal = $131,639 )
2022	2022	UNIVERSITY OF THE INCARNATE WORD	4301 BROADWAY	SAN ANTONIO	TX	78209	BEXAR	USA	Biomedical Research and Research Training	000	1	5/19/2022	NEW	$131,639
														Subtotal = $131,639

Grand Total All Awards = $406,623

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Dual Oxidase 2 as a New Target for Treatment of Diabetic Nephropathy

Award Number: SC2GM136569

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/19/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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