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Imprinted Gene Regulation by in utero Lead Exposure in Mice

Award Number: K01ES035064
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Imprinted Gene Regulation by in utero Lead Exposure in Mice - PROJECT SUMMARY The objective of this study is to determine epigenetic mechanisms that impact genomic imprinting upon in utero exposure of mice to human-relevant levels of lead (Pb). Pb is an infamous environmental exposure to human populations in the US and around the world, due in part to its neurotoxic effects. Pb exposure during early development has been linked to adverse health outcomes later in life. Preliminary data generated for this grant indicates that in utero and perinatal Pb exposure increases placenta/embryo size, and alters the DNA methylation of imprinted genes, respectively. However, the molecular mechanisms by which Pb exposure reprograms genomic imprinting during early gestation remain largely unknown. Imprinted genes are epigenetically regulated in a parent-of-origin specific manner with their mono-allelic expression driving critical periods of development. Known mechanisms of genomic imprinting include the 1) long non-coding RNA (lncRNA) and 2) insulator models, each of which program allele-specific regulation of imprinting control regions. Although dysfunctional genomic imprinting is implicated in several human diseases, the mechanisms leading to toxicant-induced imprinting dysregulation by the two models remain poorly understood. Using an established Pb exposure mouse model, this study seeks to determine in utero mechanisms that impact genomic imprinting and health effects from altered epigenetic reprogramming. Thus, female animals exposed to Pb two weeks prior to mating through 13-14 days post-conception will be used in the following Aims: 1) Determine fetal sex-specific imprinting dysregulation associated with in utero Pb exposure in mouse placenta, 2) Assess allele- and sex-specific mechanisms of in utero Pb exposure regulating genomic imprinting in the brain. Pb-exposed animals will be compared against controls to investigate genomic imprinting mechanisms in the lncRNA and insulator models by characterizing sex-, tissue-, and developmental stage-specific imprinted gene dysregulation via phenotypic, gene expression, DNA methylation, and immunohistochemical analyses. This study will reveal Pb-associated lncRNA mechanisms that inform the current epigenetic reprogramming by fetal sex. The University of Michigan provides an ideal environment to conduct the proposed research in collaboration with multiple core facilities outlined herein. The candidate will receive mentorship from a multidisciplinary team of experts to: 1) Gain proficiency in computational and statistical skills required for data analysis; 2) Acquire expertise in developmental toxicological research and mechanistic investigation; and 3) Build skills critical for leadership, teaching and mentoring, laboratory management, and grantsmanship. The proposed study will address fundamental knowledge gaps of genomic imprinting in the field to inform potential Pb-induced disease interventions. The training and research goals established in this K01 proposal constitute an exceptional foundation to ensure the candidate success in obtaining research independence.


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 = $153,877 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, THE	119 CALIFORNIA HALL	BERKELEY	CA	94720	ALAMEDA	USA	Environmental Health	001	3	4/1/2026	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$153,877
2026	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Environmental Health	000	2	3/26/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $153,877

Issue Date FY: 2025 ( Subtotal = $154,309 )
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Environmental Health	000	2	1/16/2025	NON-COMPETING CONTINUATION	$154,309
														Subtotal = $154,309

Issue Date FY: 2024 ( Subtotal = $154,309 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Environmental Health	000	1	2/12/2024	NEW	$154,309
														Subtotal = $154,309

Grand Total All Awards = $462,495

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Imprinted Gene Regulation by in utero Lead Exposure in Mice

Award Number: K01ES035064

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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