Tuesday, July 1, 2025 7/1/2025

Pioneer transcription factors in aging and neurodegeneration

Award Number: R01AG073411
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Pioneer transcription factors in aging and neurodegeneration - PROJECT SUMMARY A number of transcriptional regulators have been found to regulate the hallmarks of aging. In previous work, we found that the FOXO family of transcriptional regulators, which have been implicated in healthy aging across species, directly regulate a conserved network of target genes. In mice, FOXOs are central regulators of stem cell homeostasis during aging and are critical for tissue integrity. In humans, SNPs in the FOXO3 locus have been linked to longevity, and the upstream regulator of FOXO’s, insulin/IGF signaling must be tightly regulated to preserve healthy aging. Yet, we still lack an understanding of how FOXOs function at the chromatin level, and how their activity is altered during aging and in the context of neurodegeneration. In preliminary work, we identified for the first time the direct network of FOXO3 targets in human cells, and found that FOXOs function as pioneer factors to deploy a secondary network of transcriptional regulators to extend their target gene network. Here, we will address this critical question of the mechanisms underlying the pioneer activity, its heterogeneous nature, and how it changes in the context of aging and Alzheimer’s Disease. Completion of this work will reveal the chromatin-level changes that influence the activity of factors that counter aging and neurodegeneration, which may lead to strategies to improve associated pathologies.


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 = $518,201 )
2025	2025	BUCK INSTITUTE FOR RESEARCH ON AGING	8001 REDWOOD BLVD	NOVATO	CA	94945	MARIN	USA	Aging Research	000	6	6/4/2025	NON-COMPETING CONTINUATION	$518,201
														Subtotal = $518,201

Issue Date FY: 2024 ( Subtotal = $568,692 )
2024	2024	BUCK INSTITUTE FOR RESEARCH ON AGING	8001 REDWOOD BLVD	NOVATO	CA	94945	MARIN	USA	Aging Research	005	5	5/13/2024	NON-COMPETING CONTINUATION	$568,692
2024	2023	BUCK INSTITUTE FOR RESEARCH ON AGING	8001 REDWOOD BLVD	NOVATO	CA	94945	MARIN	USA	Aging Research	004	4	12/11/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$417,484
2024	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	003	3	12/11/2023	NON-COMPETING CONTINUATION	-$88,879
2024	2023	BUCK INSTITUTE FOR RESEARCH ON AGING	8001 REDWOOD BLVD	NOVATO	CA	94945	MARIN	USA	Aging Research	001	4	11/29/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$366,825
2024	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	3	11/28/2023	NON-COMPETING CONTINUATION	-$366,825
2024	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	002	2	12/11/2023	NON-COMPETING CONTINUATION	-$328,605
														Subtotal = $568,692

Issue Date FY: 2023 ( Subtotal = $455,704 )
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	3	5/24/2023	NON-COMPETING CONTINUATION	$455,704
														Subtotal = $455,704

Issue Date FY: 2022 ( Subtotal = $455,704 )
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	2	6/6/2022	NON-COMPETING CONTINUATION	$455,704
														Subtotal = $455,704

Issue Date FY: 2021 ( Subtotal = $449,680 )
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Aging Research	000	1	8/6/2021	NEW	$449,680
														Subtotal = $449,680

Grand Total All Awards = $2,447,981

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Pioneer transcription factors in aging and neurodegeneration

Award Number: R01AG073411

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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