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Investigating the molecular mechanisms in controlling the aryl hydrocarbon receptor protein levels

Award Number: R15ES023104
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract The aryl hydrocarbon receptor (AHR) is a ligand-activated basic-helix-loop-helix-PAS transcription factor. This receptor is responsible for our bodily response to exposure of environmental pollutants such as polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and dioxins. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most studied and best known ligand of AHR. Expression of AHR is up-regulated in human cancers and during T cell differentiation. Malfunction of the events affecting the ahr gene expression would undoubtedly cause problems in cancer, aberrant immune response, stem cell development, and our response to toxic environmental chemicals. However, our knowledge of how the AHR protein levels are maintained without ligand treatment is very limited. Our data suggested a strong likelihood that autophagy is responsible for the AHR protein degradation in human cells. In this grant proposal, we will investigate whether and how autophagy regulates the AHR protein levels in human cells. In brief, we will perform experiments to study the following aims: (1) we will determine whether the autophagy-mediated AHR protein degradation occurs in cancerous and normal human cells (Aim 1); we will determine the autophagy mechanism that is involved in the AHR degradation (Aim 2) and (3) we will investigate how triple-negative human breast cancer cells are more sensitive in the autophagy- mediated AHR protein degradation when compared to non-triple-negative breast cancer cells (Aim 3).


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 = -$36,123 )
2024	2019	UNIVERSITY OF PACIFIC	3601 PACIFIC AVE	STOCKTON	CA	95211	SAN JOAQUIN	USA	Environmental Health	000	2	4/15/2024	COMPETING CONTINUATION	-$36,123
														Subtotal = -$36,123

Issue Date FY: 2019 ( Subtotal = $382,757 )
2019	2019	UNIVERSITY OF PACIFIC	3601 PACIFIC AVE	STOCKTON	CA	95211	SAN JOAQUIN	USA	Environmental Health	000	2	8/8/2019	COMPETING CONTINUATION	$382,757
														Subtotal = $382,757

Issue Date FY: 2018 ( Subtotal = -$20,887 )
2018	2014	UNIVERSITY OF PACIFIC	3601 PACIFIC AVE	STOCKTON	CA	95211	SAN JOAQUIN	USA	Environmental Health	000	1	9/11/2018	NEW	-$20,887
														Subtotal = -$20,887

Issue Date FY: 2014 ( Subtotal = $367,058 )
2014	2014	UNIVERSITY OF THE PACIFIC	3622 STAGG WAY	STOCKTON	CA	95211	SAN JOAQUIN	USA	Environmental Health	000	1	5/26/2014	NEW	$367,058
														Subtotal = $367,058

Grand Total All Awards = $692,805

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Investigating the molecular mechanisms in controlling the aryl hydrocarbon receptor protein levels

Award Number: R15ES023104

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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