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Genetic Regulation of Inner, Middle and Outer Ear Development

Award Number: R01DC013072
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/22/2013
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Genetic Regulation of Inner, Middle and Outer Ear Development - PROJECT SUMMARY The mammalian inner, middle and outer ears have different embryonic origins, yet the development of each component of the auditory apparatus must be precisely synchronized in space and time. Understanding the mechanisms that regulate and co-ordinate the development of these structures is of central importance in understanding the basis of the many birth defects that affect hearing. We have identified a Forkhead transcription factor, Foxi3, that is expressed at very early stages in the embryonic head. Foxi3 mouse mutants made in our lab lack all components of the inner, middle and external ears. Our work suggests that one of the first steps in ear induction– the formation of the otic placode – does not occur in Foxi3 mutants. Moreover, the mesenchyme of the first and second branchial arches that generate the middle ear ossicles and the external ear begins to form in Foxi3 mutants, but rapidly succumbs to massive cell death. Moreover, we have recently identified human patients with Foxi3 variants that have a variety of defects in their hearing apparatus To our knowledge, Foxi3 is the only mammalian gene that causes a complete developmental failure of the entire inner, middle and outer ears when mutated by itself. We are therefore extremely interested to understand how Foxi3 orchestrates development of the auditory apparatus at both the cellular and molecular levels. Our data suggests that Foxi3 may act as a “pioneer” transcription factor – its main function in addition to initiating transcription is to epigenetically organize genomic loci containing ear-specific genes in a transcriptionally competent state. Our first two aims will determine the function and mechanism of Foxi3 during development of the inner ear using knockout mice, chick embryo manipulations and state-of-the-art ES cell models, deep sequencing and bioinformatic analysis. Our final aim focuses on the function the Foxi3 gene in the development of the middle and external ear – here we will both study the effects of loss of Foxi3 in mice, but also create mouse mutants that recapitulate the genetic variants seen in some of our human patients.


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 = -$14,782 )
2026	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Research Related to Deafness and Communication Disorders	002	11	12/4/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$510,780
2026	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	10	11/25/2025	NON-COMPETING CONTINUATION	$0
2026	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	001	10	12/4/2025	NON-COMPETING CONTINUATION	-$525,562
														Subtotal = -$14,782

Issue Date FY: 2025 ( Subtotal = $525,562 )
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	10	11/15/2024	NON-COMPETING CONTINUATION	$473,005
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	001	10	5/1/2025	NON-COMPETING CONTINUATION	$52,557
														Subtotal = $525,562

Issue Date FY: 2024 ( Subtotal = $525,562 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	001	9	5/2/2024	NON-COMPETING CONTINUATION	$52,557
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	9	11/15/2023	NON-COMPETING CONTINUATION	$473,005
														Subtotal = $525,562

Issue Date FY: 2023 ( Subtotal = $525,562 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	001	8	1/13/2023	NON-COMPETING CONTINUATION	$52,557
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	8	11/17/2022	NON-COMPETING CONTINUATION	$473,005
														Subtotal = $525,562

Issue Date FY: 2022 ( Subtotal = $521,482 )
2022	2022	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	7	11/18/2021	NON-COMPETING CONTINUATION	$469,333
2022	2022	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	001	7	4/22/2022	NON-COMPETING CONTINUATION	$52,149
														Subtotal = $521,482

Issue Date FY: 2021 ( Subtotal = $529,132 )
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	6	10/29/2020	COMPETING CONTINUATION	$529,132
														Subtotal = $529,132

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	5	6/25/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	5	1/17/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $451,064 )
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	5	2/21/2017	NON-COMPETING CONTINUATION	$405,957
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	001	5	5/24/2017	NON-COMPETING CONTINUATION	$45,107
														Subtotal = $451,064

Issue Date FY: 2016 ( Subtotal = $451,064 )
2016	2016	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	4	2/25/2016	EXTENSION WITH OR WITHOUT FUNDS	$451,064
														Subtotal = $451,064

Issue Date FY: 2015 ( Subtotal = $506,769 )
2015	2015	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	3	2/25/2015	NON-COMPETING CONTINUATION	$506,769
														Subtotal = $506,769

Issue Date FY: 2014 ( Subtotal = $614,276 )
2014	2014	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	001	2	8/26/2014	SUPPLEMENT FOR EXPANSION	$69,977
2014	2014	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	2	3/7/2014	NON-COMPETING CONTINUATION	$544,299
														Subtotal = $614,276

Issue Date FY: 2013 ( Subtotal = $483,477 )
2013	2013	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	001	1	7/15/2013	SUPPLEMENT FOR EXPANSION	$32,413
2013	2013	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Research Related to Deafness and Communication Disorders	000	1	3/22/2013	NEW	$451,064
														Subtotal = $483,477

Grand Total All Awards = $5,119,168

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Genetic Regulation of Inner, Middle and Outer Ear Development

Award Number: R01DC013072

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/22/2013

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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