Thursday, January 1, 2026 1/1/2026

Role of Aflatoxin-induced DNA Damage Formation and Repair in Hepatic Mutagenesis

Award Number: R00ES030015
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: 09/03/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Role of Aflatoxin-induced DNA Damage Formation and Repair in Hepatic Mutagenesis - ABSTRACT / PROJECT SUMMARY Aflatoxin, produced by the fungi Aspergillus flavus and Aspergillus parasiticus, is a well-known environmental carcinogen that causes mutations and ultimately leads to hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths worldwide. Chronic dietary exposure to aflatoxin B1 (AFB1), the most mutagenic aflatoxin, and chronic infections with the hepatitis B virus (HBV) or hepatitis C virus (HCV) are the two major etiological factors for the development of HCC. Nucleotide excision repair is the repair mechanism by which the bulky lesions induced by AFB1 are removed from the genome. Despite the progress in our knowledge of the AFB1-DNA adduct, the formation and removal kinetics of the bulky DNA lesion throughout the genome and the factors affecting the damage formation and repair efficiency remain elusive. Our long-term goal of this project is to better understand how the kinetics of AFB1-induced DNA damage formation and repair contributes to human hepatic mutagenesis. The overall objective of this particular proposal, which is an initial step to achieve our long-term goal, is to combine biochemistry, genetics, adductomics and computational approaches to investigate effects of histone modifications and three-dimensional (3D) genome organization on AFB1-induced DNA damage formation and repair, and to determine the correlations between AFB1-DNA adduct spectra or repair efficiencies and mutational spectra of AFB1 in human HCC. Our central hypothesis is that human hepatic mutagenesis correlates with the AFB1-induced DNA damage formation and/or repair events, which are affected by histone modifications and 3D genome organization. We propose two specific aims to test our hypothesis and accomplish the objective: 1)! Genome-wide Analysis of AFB1-induced DNA Damage Formation and Repair Kinetics as a Function of Histone Modifications and 3D Genome Organization (Aim1, K99 and R00 phase). 2) Determine the Correlations Between AFB1-DNA Adduct Spectra or Repair Efficiencies and Mutational Spectra of AFB1 in Human HCC (Aim2, R00 phase). We expect the following outcomes: Determination of the effect of histone acetylation on AFB1-DNA adducts formation and repair efficiency; determination of the effect of 3D genome organization on AFB1-DNA adducts formation and repair efficiency; identification of AFB1-induced DNA damage hot spots and repair cold spots in cancer-associated genes; determination of the correlations between AFB1-DNA adduct spectra or repair efficiencies and mutational spectra of AFB1 in human HCC. The proposed research is significant because it will give insights into development of AFB1-associated HCC, improve prevention strategies and develop better treatment for HCC.


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: 2026 ( Subtotal = $0 )
2026	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Environmental Health	000	4	12/5/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Environmental Health	000	4	7/10/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $248,335 )
2022	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Environmental Health	000	4	8/9/2022	NON-COMPETING CONTINUATION	$248,335
														Subtotal = $248,335

Issue Date FY: 2021 ( Subtotal = $250,367 )
2021	2021	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Environmental Health	001	3	7/13/2021	NON-COMPETING CONTINUATION	$249,000
2021	2020	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Environmental Health	000	2	1/31/2021	EXTENSION WITH OR WITHOUT FUNDS	$1,367
														Subtotal = $250,367

Issue Date FY: 2020 ( Subtotal = $249,000 )
2020	2020	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Environmental Health	000	2	9/3/2020	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $747,702

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Role of Aflatoxin-induced DNA Damage Formation and Repair in Hepatic Mutagenesis

Award Number: R00ES030015

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: 09/03/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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