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Urinary Biomarkers of Renal Mitochondrial Dysfunction

Award Number: R41ES023767
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2013
PERIOD OF PERFORMANCE END DATE: 05/31/2016

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Urinary Biomarkers of Renal Mitochondrial Dysfunction - DESCRIPTION (provided by applicant): The long-term goal of this project is to identify and validate biomarkers of mitochondrial dysfunction due to environmental stressors. Diverse acute insults from surgery, trauma, ischemia/reperfusion (I/R) and drug and environmental chemical toxicity lead to mitochondrial dysfunction and result in cell injury and death in many organs/tissues (e.g. heart, lung, brain, liver and kidney). Furthermore, mitochondrial dysfunction can contribute to cell injury through increased production of reactive oxygen and nitrogen species. Mitochondrial dysfunction is also a component of many chronic diseases such as metabolic syndrome, diabetes, neurodegenerative diseases, and aging. Consequently, there is a great need for non-invasive biomarkers of mitochondrial dysfunction. We hypothesize that urinary mitochondrial DNA (mtDNA) and urinary protein levels of mitochondrial ATP synthase (ATPS) subunits are sensitive and specific markers of mitochondrial dysfunction in acute kidney injury (AKI). Our preliminary studies support this hypothesis by demonstrating increased urinary mtDNA and ATPS in mice subjected to I/R induced AKI when renal mitochondrial dysfunction was present. These preliminary studies provide strong evidence in support of our hypothesis. The following Specific Aims will be examined: 1) Using a mouse model with different degrees of I/R induced AKI, elucidate urinary changes in mtDNA, mitochondrial ATPS subunits and other mitochondrial proteins; integrate these changes with renal mitochondrial dysfunction over time; and compare and contrast the changes in these endpoints with general urinary AKI biomarkers. These studies will result in new urinary markers of mitochondrial dysfunction in animals. Comparison of mitochondrial DNA, protein and function over a range of times and grades of injury will permit better understanding of the timing and mechanisms of injury and recovery. Finally, these biomarkers can be tested in humans and translated into laboratory and clinical practice.


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: 2018 ( Subtotal = -$52,478 )
2018	2013	MITOHEALTH, INC	280 CALHOUN ST	CHARLESTON	SC	29425	CHARLESTON	USA	Environmental Health	000	2	9/30/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$52,478
														Subtotal = -$52,478

Issue Date FY: 2015 ( Subtotal = $0 )
2015	2013	SCHNELLGEN INC	280 CALHOUN STREET	CHARLESTON	SC	29425	CHARLESTON	USA	Environmental Health	000	1	5/5/2015	NEW	-$194,211
2015	2013	MITOHEALTH INC	POST OFFICE BOX 1572	MOUNT PLEASANT	SC	29465	CHARLESTON	USA	Environmental Health	001	2	5/6/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$194,211
														Subtotal = $0

Issue Date FY: 2013 ( Subtotal = $275,219 )
2013	2013	SCHNELLGEN INC	280 CALHOUN STREET	CHARLESTON	SC	29425	CHARLESTON	USA	Environmental Health	000	1	8/15/2013	NEW	$275,219
														Subtotal = $275,219

Grand Total All Awards = $222,741

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Urinary Biomarkers of Renal Mitochondrial Dysfunction

Award Number: R41ES023767

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2013

PERIOD OF PERFORMANCE END DATE: 05/31/2016

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