Thursday, February 19, 2026 2/19/2026

Significance of Myo7a isoforms in hair cell function

Award Number: R01DC018842
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: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2031

Group Awards By:

View Award Description

Significance of Myo7a isoforms in hair cell function - Hair cells in the cochlea rely on Myosin 7a (MYO7A) for mechanotransduction (MET), with MYO7A playing a key role in tip-link tension and sensitivity. Our previous studies revealed multiple MYO7A isoforms with distinct expression patterns in inner (IHCs) and outer hair cells (OHCs), suggesting functional specialization. This project continues to investigate the roles of these isoforms in tip-link tension, cochlear mechanics, tip-link repair, and transcriptional regulation, providing insights relevant for gene therapy. Aim 1 explores MYO7A’s role in tip-link tension and frequency tuning. We identified two isoforms, MYO7A-C and MYO7A-N, with different ATPase activities and structural properties. IHCs primarily express MYO7A-C, while OHCs express both in a tonotopic gradient. To isolate isoform-specific effects, we developed a MYO7A-CtoN mouse model, in which MYO7A-N is exclusively expressed in all hair cells. Using electrophysiology, optical coherence tomography and hearing function tests, we will test whether MYO7A functions as a tensioning motor or a passive anchor. Aim 2 investigates MYO7A’s role in tip-link repair. Tip links regenerate after breakage, but the molecular mechanisms remain unclear. We hypothesize that MYO7A transports tip-link components to the upper insertion site during recovery. Using an auxin-inducible degradation (AID) system in mice, we will rapidly deplete MYO7A after tip-link disruption and assess tip-link restoration using electron microscopy, immunofluorescence, and MET electrophysiology. Additionally, we will determine whether MYO7A isoforms differentially contribute to repair. Aim 3 examines MYO7A transcriptional regulation. We identified an intronic enhancer (Enhancer A) that modulates MYO7A’s tonotopic expression, with deletion (ΔEnhA mice) leading to reduced expression towards the cochlear base. ChIP-Seq data suggest the transcription factor SIX2 binds to this enhancer. To validate this, we will test Enhancer sufficiency via AAV delivery, confirm SIX2 binding, and generate a SIX2-binding site mutant (MYO7A-N-HAEnhASix2Δ mouse) to assess its impact on MYO7A expression and hearing. This study will define MYO7A isoform function in cochlear mechanics and repair, uncover regulatory elements controlling its expression, and inform gene therapy strategies by identifying essential isoforms and hair cell-specific promoters.


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 = $550,334 )
2026	2026	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Research Related to Deafness and Communication Disorders	001	6	1/22/2026	COMPETING CONTINUATION	$550,334
2026	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Research Related to Deafness and Communication Disorders	000	5	1/22/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $550,334

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Research Related to Deafness and Communication Disorders	000	5	8/19/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $474,378 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Research Related to Deafness and Communication Disorders	000	5	8/20/2024	NON-COMPETING CONTINUATION	$474,378
														Subtotal = $474,378

Issue Date FY: 2023 ( Subtotal = $474,378 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Research Related to Deafness and Communication Disorders	000	4	8/3/2023	NON-COMPETING CONTINUATION	$474,378
														Subtotal = $474,378

Issue Date FY: 2022 ( Subtotal = $468,343 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Research Related to Deafness and Communication Disorders	001	3	8/15/2022	NON-COMPETING CONTINUATION	$468,533
2022	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Research Related to Deafness and Communication Disorders	000	2	3/29/2022	NON-COMPETING CONTINUATION	-$190
														Subtotal = $468,343

Issue Date FY: 2021 ( Subtotal = $484,098 )
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Research Related to Deafness and Communication Disorders	000	2	8/10/2021	NON-COMPETING CONTINUATION	$484,098
														Subtotal = $484,098

Issue Date FY: 2020 ( Subtotal = $489,753 )
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Research Related to Deafness and Communication Disorders	001	1	7/7/2020	NEW	$0
2020	2020	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Research Related to Deafness and Communication Disorders	000	1	6/26/2020	NEW	$489,753
														Subtotal = $489,753

Grand Total All Awards = $2,941,284

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Significance of Myo7a isoforms in hair cell function

Award Number: R01DC018842

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: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2031

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer