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The Imprinted Gene Network in the programming of Non-Alcoholic Fatty Liver Disease by early life cadmium exposure

Award Number: R01ES031596
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 The toxic metal cadmium (Cd) is one of the top ten chemicals of major public health concern identified by the World Health Organization. Cd exerts toxic effects on the kidneys, respiratory and skeletal systems, and long- term exposure is associated with metabolic, cardiovascular and behavioral disorders. We and others have shown that exposure to Cd during early life can lead to disease in adulthood. One of these diseases is non- alcoholic fatty liver disease (NAFLD), characterized by fat accumulation, inflammation and tissue damage in the liver. NAFLD affects 30-40 % of the US adult population, and patients with NAFLD have a higher risk of developing liver cancer. The broad, long-term objectives of this project are to understand the mechanisms that link early life Cd exposure to NAFLD in adulthood, and to use this knowledge to develop strategies that can prevent or reverse this disease. To this end, we have collected data from pregnant women and their children in North Carolina and demonstrated that DNA isolated from newborn cord blood carries molecular `signatures' of Cd exposure. We propose that these signatures play an important role in Cd-induced NAFLD. In the current proposal, we will use mouse and cell culture models to test this hypothesis, and determine how events at the molecular level lead to disease. We propose three specific aims: 1) determine whether the molecular signatures associated with Cd that we observe in humans cause changes to the activity of a set of genes called imprinted genes, which play important roles in liver metabolism; 2) understand how changes to imprinted gene activity lead to NAFLD; and 3) determine whether Cd could cause NAFLD solely through influencing the activity of these genes. We aim to demonstrate that imprinted genes play a central role in linking early life Cd exposure to NAFLD in adulthood, thereby identifying potential markers of disease susceptibility and providing opportunities for treatment prior to disease onset.


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 = $391,219 )
2024	2024	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Environmental Health	001	5	4/2/2024	SUPPLEMENT FOR EXPANSION	$74,204
2024	2024	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27695	WAKE	USA	Environmental Health	000	5	4/1/2024	NON-COMPETING CONTINUATION	$317,015
														Subtotal = $391,219

Issue Date FY: 2023 ( Subtotal = $398,744 )
2023	2023	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27607	WAKE	USA	Environmental Health	001	4	4/1/2023	SUPPLEMENT FOR EXPANSION	$80,284
2023	2023	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27607	WAKE	USA	Environmental Health	000	4	3/31/2023	NON-COMPETING CONTINUATION	$318,460
														Subtotal = $398,744

Issue Date FY: 2022 ( Subtotal = $321,515 )
2022	2022	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27607	WAKE	USA	Environmental Health	000	3	3/28/2022	NON-COMPETING CONTINUATION	$321,515
														Subtotal = $321,515

Issue Date FY: 2021 ( Subtotal = $321,991 )
2021	2021	NORTH CAROLINA STATE UNIVERSITY	2601 WOLF VILLAGE WAY	RALEIGH	NC	27607	WAKE	USA	Environmental Health	000	2	3/24/2021	NON-COMPETING CONTINUATION	$321,991
														Subtotal = $321,991

Issue Date FY: 2020 ( Subtotal = $316,879 )
2020	2020	NORTH CAROLINA STATE UNIVERSITY	2701 SULLIVAN DR STE 240	RALEIGH	NC	27695	WAKE	USA	Environmental Health	000	1	5/18/2020	NEW	$316,879
														Subtotal = $316,879

Grand Total All Awards = $1,750,348

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The Imprinted Gene Network in the programming of Non-Alcoholic Fatty Liver Disease by early life cadmium exposure

Award Number: R01ES031596

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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