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High Throughput Mitochondrial Nephrotoxicant Assay

Award Number: R44ES019378
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: 09/30/2010
PERIOD OF PERFORMANCE END DATE: 08/31/2015

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High Throughput Mitochondrial Nephrotoxicant Assay - DESCRIPTION (provided by applicant): The kidney is a target of toxicity from drugs, and industrial and environmental chemicals because of its high blood flow, numerous transporters, and reliance on aerobic metabolism. Not surprisingly, mitochondria are a common intracellular target of chemicals in multiple organs, leading to decreased aerobic metabolism and ATP, and cell death. Current in vitro models of nephrotoxicity and mitochondrial damage are inadequate for many of the same reasons: cultured cells are very glycolytic with minimal aerobic metabolism, and there are no moderate or high-throughput real-time metabolomic assays. Consequently, new cellular models and metabolomic methodologies are needed to evaluate nephrotoxicity and mitochondrial damage. We have developed primary cultures of renal proximal tubular cells (RPTC) that exhibit in vivo levels of aerobic metabolism, are not glycolytic and retain higher levels of differentiated functions. We previously developed primary cultures of renal proximal tubular cells (RPTC) that exhibit in vivo levels of aerobic metabolism, are not glycolytic, and retain higher levels of differentiated functions. The goal of the Phase I proposal was to merge our novel and relevant RPTC model and the Seahorse technology to develop a high-throughput assay to accurately measure nephrotoxicity. In addition to completing the objectives described in the Phase I aims, we also developed a cheminformatic strategy in which chemical similarity is used to cluster molecules that are then modeled to define a potential "toxicophore" of similar physicochemical features in 3-dimesional space. These chemical entities/toxicophores that damage mitochondria are predicted to be nephrotoxicants. Our goals for Phase are to validate our integrated metabolic and imaging assay using the TOXNET & Toxcast land to use cheminformatic analyses to develop a toxicophore database. This RPTC/Seahorse platform will identify nephrotoxicants and mitochondrial toxicants and provide public companies and regulatory agencies with mechanism and chemical-based criteria for assessing and predicting nephrotoxicity and mitochondrial toxicity of new drugs, consumer products, and environmental agents, and shorten the overall time to identify potential problem chemicals. The commercialization plan is to offer these screening and cheminformatic services to pharmaceutical & federal agencies.


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: 2017 ( Subtotal = -$175,044 )
2017	2012	MITOHEALTH, INC	280 CALHOUN ST	CHARLESTON	SC	29425	CHARLESTON	USA	Environmental Health	000	3	9/26/2017	NON-COMPETING CONTINUATION	-$175,044
														Subtotal = -$175,044

Issue Date FY: 2015 ( Subtotal = $0 )
2015	2012	MITOHEALTH INC	POST OFFICE BOX 1572	MOUNT PLEASANT	SC	29465	CHARLESTON	USA	Environmental Health	000	3	11/19/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $800,744 )
2012	2012	MITOHEALTH INC	POST OFFICE BOX 1572	MOUNT PLEASANT	SC	29465	CHARLESTON	USA	Environmental Health	000	3	8/13/2012	NON-COMPETING CONTINUATION	$800,744
														Subtotal = $800,744

Issue Date FY: 2011 ( Subtotal = $807,378 )
2011	2011	MITOHEALTH INC	POST OFFICE BOX 1572	MOUNT PLEASANT	SC	29465	CHARLESTON	USA	Environmental Health	000	2	9/16/2011	COMPETING CONTINUATION	$807,378
														Subtotal = $807,378

Grand Total All Awards = $1,433,078

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High Throughput Mitochondrial Nephrotoxicant Assay

Award Number: R44ES019378

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: 09/30/2010

PERIOD OF PERFORMANCE END DATE: 08/31/2015

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