Saturday, July 5, 2025 7/5/2025

Heterochromatin as a barrier to regeneration in the mouse cochlea

Award Number: F31DC018703
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2023

Group Awards By:

View Award Description

Heterochromatin as a barrier to regeneration in the mouse cochlea - PROJECT SUMMARY/ABSTRACT The main cause of hearing loss is damage of cochlear sensory hair cells within the inner ear. The long-term objective of the Segil lab is to treat human deafness through the regeneration of lost sensory hair cells within the organ of Corti. A potential strategy for hair cell regeneration is to induce surviving supporting cells in long- deafened inner ears to transdifferentiate into new functional hair cells. In early perinatal mice, upregulation of the hair-cell specific transcription factor ATOH1, or disruption of Notch lateral inhibition in supporting cells, is sufficient to induce transdifferentiation. However, supporting cells quickly lose the potential to transdifferentiate within one week after birth. The loss of this plasticity may be due to epigenetic maturation, wherein the spread of heterochromatin in perinatal supporting cells represses hair cell- specific gene regulatory networks required for transdifferentiation. Heterochromatin are highly condensed regions of nuclear DNA associated with gene silencing, and it has cell-type specific characteristics that acquires during development. Epigenetic marks of heterochromatin include DNA methylation, H3K9 methylation, and H3K27 methylation. My preliminary data shows that blocking DNA methylation is sufficient to prolong the window of transdifferentiation potential in postnatally maturing supporting cells. Additionally, I have shown that SCs gradually gain DNA methylation as they mature from P1 to P21. This project hypothesizes that postnatally maturing supporting cells gain heterochromatin-associated DNA methylation and H3K9 methylation to repress hair cell gene regulatory networks required for transdifferentiation. Aim 1 will characterize the changes in DNA methylation between postnatal day 1 and 6-week old supporting cells of the organ of Corti, as well as test the DAPT-induced transdifferentiation response after blocking DNA methylation gain. Aim 2 will examine the changes in H3K9 methylation between postnatal day 1 and 6-week old supporting cells, as well as test the DAPT-induced transdifferentiation response after blocking H3K9 methylation gain. These two aims will elucidate how the spread of heterochromatic features in postnatally maturing supporting cells may contribute to the loss of transdifferentiation potential, which will which will guide future endeavors to regenerate hair cells and restore hearing.


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 = -$12,447 )
2024	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	001	3	3/12/2024	NON-COMPETING CONTINUATION	$1,522
2024	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	002	3	4/24/2024	NON-COMPETING CONTINUATION	-$1
2024	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90089	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	000	3	3/8/2024	NON-COMPETING CONTINUATION	-$13,968
														Subtotal = -$12,447

Issue Date FY: 2023 ( Subtotal = $47,694 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	000	3	12/23/2022	NON-COMPETING CONTINUATION	$46,752
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Research Related to Deafness and Communication Disorders	001	3	2/5/2023	NON-COMPETING CONTINUATION	$942
														Subtotal = $47,694

Issue Date FY: 2022 ( Subtotal = $46,752 )
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	2	4/25/2022	NON-COMPETING CONTINUATION	$717
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	002	2	5/19/2022	NON-COMPETING CONTINUATION	-$1
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	003	2	8/11/2022	NON-COMPETING CONTINUATION	$0
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	2	12/21/2021	NON-COMPETING CONTINUATION	$46,036
														Subtotal = $46,752

Issue Date FY: 2020 ( Subtotal = $45,520 )
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	000	1	9/4/2020	NEW	$45,520
														Subtotal = $45,520

Grand Total All Awards = $127,519

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Heterochromatin as a barrier to regeneration in the mouse cochlea

Award Number: F31DC018703

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer