Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Mechanisms of protection from noise-induced hearing loss

Award Number: R01DC019426
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: 02/18/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

Group Awards By:

View Award Description

Mechanisms of protection from noise-induced hearing loss - TITLE Mechanisms of protection from noise-induced hearing loss ABSTRACT The cellular and molecular bases underlying noise-induced hearing loss (NIHL), the second leading cause of hearing loss globally, are to date, not understood presenting a barrier to the prediction of risk, the prevention, and ultimately the treatment of this debilitating disease. 1.1 billion young people (aged between 12-35 years) are at risk of hearing loss due to exposure to noise in recreational settings. Among Service Members of Operation Enduring Freedom and Iraqi Freedom, NIHL and its associated tinnitus are the top two diagnoses and unaddressed hearing loss poses an annual global cost of $750 billion US dollars. Noise attenuation and hearing aids currently represent the only measures for protection and treatment, respectively. It is now clear that cochlear synaptic loss precedes hair cell loss at low-moderate noise exposures (nonexplosive) effectively silencing affected neurons. Our laboratory and others have illuminated genetic mechanisms that modify sensitivity to NIHL in mice and humans. Through mouse GWAS we have identified a critical gene, Prkag2 encoding the g2 subunit of the AMPK complex. We find that damaging noise leads to nuclear AMPK activity specifically in inner hair cells and that Prkag2 deficient mice are susceptible to NIHL due to greater instability of the inner hair cell presynaptic ribbon. There is an urgent need to identify directed therapies aimed at the prevention and/or repair of cochlear damage from noise exposure, for which an understanding of the underlying mechanisms is an obligate prerequisite. Toward the long-term goal of developing targeted therapies for the prevention and/or correction of noise-induced synaptopathy, we now seek to decipher the pathways and mechanisms linking nuclear AMPK activity in inner hair cells to NIHL. Based upon our preliminary data, our central hypothesis is that AMPK becomes activated and trapped in the nucleus of inner but not outer hair cells by intranuclear phosphorylation after noise exposure and subsequently regulates the expression of downstream targets that impact the number and volume of presynaptic ribbons. Using a combination of genetics, physiology, cell biology, biochemistry, and structural biology, we propose the following three aims: the identification of cellular factors associated with susceptibility to NIHL (Aim 1), the molecular basis of nucleocytoplasmic shuttling of AMPK (Aim 2), and the identification of additional factors in the AMPK pathway leading to susceptibility to NIHL (Aim 3). As the AMPK pathway is fundamental to cell survival, metabolism, gene regulation, and hearing, and is targetable, the completion of these aims has the potential to lead to meaningful interventions for this debilitating condition.


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 = $688,388 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	000	5	2/26/2026	NON-COMPETING CONTINUATION	$688,388
														Subtotal = $688,388

Issue Date FY: 2025 ( Subtotal = $693,916 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	001	4	5/28/2025	NON-COMPETING CONTINUATION	$69,392
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	000	4	2/14/2025	NON-COMPETING CONTINUATION	$624,524
														Subtotal = $693,916

Issue Date FY: 2024 ( Subtotal = $699,176 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	000	3	1/10/2024	NON-COMPETING CONTINUATION	$629,258
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	001	3	5/7/2024	NON-COMPETING CONTINUATION	$69,918
														Subtotal = $699,176

Issue Date FY: 2023 ( Subtotal = $726,545 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	000	2	1/25/2023	NON-COMPETING CONTINUATION	$726,545
														Subtotal = $726,545

Issue Date FY: 2022 ( Subtotal = $773,286 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Related to Deafness and Communication Disorders	000	1	2/18/2022	NEW	$773,286
														Subtotal = $773,286

Grand Total All Awards = $3,581,311

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms of protection from noise-induced hearing loss

Award Number: R01DC019426

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: 02/18/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer