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The Role of Aquaporin 3 in Arsenic-Induced DNA Damage and Mutagenesis

Award Number: R00ES033259
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: 08/15/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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The Role of Aquaporin 3 in Arsenic-Induced DNA Damage and Mutagenesis - PROJECT SUMMARY Arsenic is a widespread toxin in drinking water that affects millions of people, increasing the risks of neurodegenerative and cardiovascular diseases and cancers. High doses of arsenic cause DNA damage and genome instability. However, the health effects associated with low-dose arsenic are controversial. Recently, we discovered that large networks of DNA damageome proteins (DDPs) promote DNA damage and genome instability (Xia et al. Cell 2019). We also found that Aquaporin 3 (AQP3) is a new lung cancer-associated DDP. This application describes the mechanism by which AQP3 interacts with low-dose arsenic to promote DNA damage, an approach to map AQP3, arsenic-induced double-strand break (DSB) hotspots, and associated mutation signatures in human cells and populations. Specifically, it will (1) provide mechanistic insights into how AQP3 potentiates arsenic-induced DNA Damage, (2) map DSBs caused by AQP3 and low-dose arsenic interactions, and (3) identify AQP3 and arsenic-induced genome instability and mutational signatures. The proposed studies will bring function to endogenous DNA damage and the DNA damageome proteins when interacting with environmental toxicants. Mechanistic insights into how low-dose arsenic interacts with risk genes are critical knowledge for the prevention, diagnosis, and treatment of arsenic-associated diseases. This project will identify early biomarkers to predict the long-term health impacts of arsenic, and uncover mutational signatures to infer cancer etiology and reveal past arsenic exposure. Lastly, the platform developed in this proposal will be useful for uncovering the effects of environmental toxicants and/or carcinogens with host genes. In addition to its scientific proposal, this application also lays out a comprehensive training plan that will help the candidate achieve his career goal of becoming an independent investigator who will apply his unique background in endogenous DNA damage to better understand genes-exogenous environmental agents (e.g. arsenic) interactions. Further interdisciplinary knowledge in environmental health, formal bioinformatics, and quantitative genomics training, as well as CRISPR and organoid training will put him in a unique position to tackle challenging environmental health research problems. Dr. Chris Amos, Director of the Institute for Clinical and Translational Research at the Baylor College of Medicine will lead a group of co-mentors and advisory committee members to provide advice on research and career development with advancement to a tenure track position.


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	2024	CREIGHTON UNIVERSITY	2500 CALIFORNIA PLAZA	OMAHA	NE	68178	DOUGLAS	USA	Environmental Health	000	4	1/22/2025	NON-COMPETING CONTINUATION	-$176,635
2025	2024	CREIGHTON UNIVERSITY	2500 CALIFORNIA PLAZA	OMAHA	NE	68178	DOUGLAS	USA	Environmental Health	002	4	4/30/2025	NON-COMPETING CONTINUATION	-$1,588
2025	2024	TEXAS A & M UNIVERSITY SYSTEM HEALTH SCIENCE CENTER	6003 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Environmental Health	001	5	1/23/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$176,635
2025	2024	TEXAS A & M UNIVERSITY SYSTEM HEALTH SCIENCE CENTER	6003 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Environmental Health	003	5	4/30/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,588
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $236,245 )
2024	2024	CREIGHTON UNIVERSITY	2500 CALIFORNIA PLAZA	OMAHA	NE	68178	DOUGLAS	USA	Environmental Health	000	4	7/31/2024	NON-COMPETING CONTINUATION	$236,245
														Subtotal = $236,245

Issue Date FY: 2023 ( Subtotal = $246,221 )
2023	2023	CREIGHTON UNIVERSITY	2500 CALIFORNIA PLAZA	OMAHA	NE	68178	DOUGLAS	USA	Environmental Health	000	3	7/25/2023	NON-COMPETING CONTINUATION	$246,221
														Subtotal = $246,221

Issue Date FY: 2022 ( Subtotal = $249,000 )
2022	2022	CREIGHTON UNIVERSITY	2500 CALIFORNIA PLAZA	OMAHA	NE	68178	DOUGLAS	USA	Environmental Health	000	2	8/8/2022	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $731,466

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The Role of Aquaporin 3 in Arsenic-Induced DNA Damage and Mutagenesis

Award Number: R00ES033259

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: 08/15/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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