Thursday, November 21, 2024 11/21/2024

Epigenetic mechanisms underlying the failure of hair cell regeneration in mammals

Award Number: R01DC015829
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract: Sensory hair cell regeneration does not occur spontaneously in the mature mammalian organ of Corti, making hearing loss permanent. The goal of this proposal is to identify the causes and mechanisms behind the failure of hair cell regeneration, as well as ways to stimulate regeneration in surviving populations of inner ear supporting cells in deafened individuals. Our primary hypothesis is that regeneration requires the re- engagement of developmental gene networks to guide supporting cells to a hair cell fate, and that during postnatal inner ear maturation, epigenetic barriers arise that block the re-activation of these gene networks. The goal is to develop methods to overcome these epigenetic barriers, and to establish new cell fates with regenerative potential within the organ of Corti. Experimentally, perinatal mice retain a latent capacity for direct supporting cell transdifferentiation to a hair cell-like fate, but this capacity is rapidly lost in the first weeks after birth. This age-dependent change in regenerative potential provides a window through which to investigate the transition from a permissive to a non-permissive state for this form of regeneration in the normally maturing organ of Corti. The work of this proposal is to elucidate the mechanism(s) of epigenetic control of transdifferentiation in perinatal supporting cells (Aim1) and to identify the machinery of maturation-related changes in epigenetic/chromatin structure in supporting cells of the inner ear. (Aim 2). We hypothesize that these changes are responsible for the failure of regeneration. Finally, to investigate the epigenetic structure of adult supporting cell chromatin in normal and deafened mice (Aim 3). We hypothesize that manipulation of the epigenetic state is an important approach for future regenerative medicine approaches to restoring lost hair cells.


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 = -$11,819 )
2025	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	000	5	10/21/2024	NON-COMPETING CONTINUATION	-$11,819
														Subtotal = -$11,819

Issue Date FY: 2022 ( Subtotal = $581,595 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	000	5	6/21/2022	NON-COMPETING CONTINUATION	$581,595
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	001	5	8/31/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $581,595

Issue Date FY: 2021 ( Subtotal = $581,595 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	000	4	6/29/2021	NON-COMPETING CONTINUATION	$581,595
														Subtotal = $581,595

Issue Date FY: 2020 ( Subtotal = $581,595 )
2020	2020	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	001	3	6/23/2020	NON-COMPETING CONTINUATION	$581,595
2020	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	000	2	12/12/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $581,595

Issue Date FY: 2019 ( Subtotal = $566,168 )
2019	2019	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	000	2	6/20/2019	NON-COMPETING CONTINUATION	$566,168
														Subtotal = $566,168

Issue Date FY: 2018 ( Subtotal = $510,465 )
2018	2018	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	000	1	6/27/2018	NEW	$510,465
														Subtotal = $510,465

Grand Total All Awards = $2,809,599

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Epigenetic mechanisms underlying the failure of hair cell regeneration in mammals

Award Number: R01DC015829

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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