Thursday, April 3, 2025 4/3/2025

Molecular mechanism in noise-induced hearing loss

Award Number: R01DC009222
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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Molecular mechanism in noise-induced hearing loss - ABSTRACT The long-term goals of this research are to elucidate the molecular mechanisms underlying noise-induced hearing loss (NIHL) and to propose rational therapeutic interventions for prevention. Based on our previous findings and consistent with findings in other systems, we will test the hypothesis that prolonged activation of AMPKα (T172) by calcium/calmodulin-dependent kinase kinase 2 (CaMKK2) and liver kinase B1 (LKB1) or reactive oxygen species (ROS) triggers outer hair cell (OHC) death. We further propose that activated CaMKK2 facilitates translocation of nuclear factor of activated T-cells (NFAT) into OHC nuclei, causing release of cytokine genes. Finally, we will use siRNA and pharmacological compounds to block multiple death pathways for potential synergistic protection against NIHL. We will employ a comprehensive experimental approach including in-vivo studies with adult mice to define the underlying molecular mechanisms using short hairpin RNA (shRNA) via virus transfection, single cell RNA-seq (scRNA-seq) with gene set enrichment analysis (GSEA), and fluorescence in-situ hybridization with RNAscope. These studies investigating innovative therapeutic strategies are designed to identify novel avenues for the prevention of NIHL, benefiting the quality of life of affected individuals and reducing healthcare costs. In addition, the data generated by this proposal will make a significant contribution to our understanding of a broad range of inner ear disorders since similarities have been shown in the molecular events associated with noise-induced, drug-induced, and age-related hearing loss.


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 = $348,991 )
2025	2025	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	15	3/1/2025	NON-COMPETING CONTINUATION	$348,991
														Subtotal = $348,991

Issue Date FY: 2024 ( Subtotal = $392,534 )
2024	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	14	2/21/2024	NON-COMPETING CONTINUATION	$353,281
2024	2024	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	001	14	5/2/2024	NON-COMPETING CONTINUATION	$39,253
														Subtotal = $392,534

Issue Date FY: 2023 ( Subtotal = $677,181 )
2023	2023	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	001	13	3/22/2023	SUPPLEMENT FOR EXPANSION	$338,331
2023	2023	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	13	2/20/2023	NON-COMPETING CONTINUATION	$338,850
														Subtotal = $677,181

Issue Date FY: 2022 ( Subtotal = $339,665 )
2022	2022	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	002	12	2/18/2022	COMPETING CONTINUATION	$339,665
2022	2022	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	004	12	7/13/2022	COMPETING CONTINUATION	$132,187
2022	2020	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	001	11	2/14/2022	NON-COMPETING CONTINUATION	$0
2022	2020	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	003	11	7/13/2022	NON-COMPETING CONTINUATION	-$132,187
2022	2020	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	11	11/18/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $339,665

Issue Date FY: 2020 ( Subtotal = $317,688 )
2020	2020	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	11	12/17/2019	NON-COMPETING CONTINUATION	$285,919
2020	2020	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	001	11	1/17/2020	NON-COMPETING CONTINUATION	$31,769
														Subtotal = $317,688

Issue Date FY: 2019 ( Subtotal = $317,688 )
2019	2019	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	10	12/14/2018	NON-COMPETING CONTINUATION	$317,688
														Subtotal = $317,688

Issue Date FY: 2018 ( Subtotal = $317,688 )
2018	2018	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	9	12/28/2017	NON-COMPETING CONTINUATION	$285,919
2018	2018	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	001	9	4/4/2018	NON-COMPETING CONTINUATION	$31,769
														Subtotal = $317,688

Issue Date FY: 2017 ( Subtotal = $317,688 )
2017	2017	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	8	12/16/2016	NON-COMPETING CONTINUATION	$285,919
2017	2017	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	001	8	5/24/2017	NON-COMPETING CONTINUATION	$31,769
														Subtotal = $317,688

Issue Date FY: 2016 ( Subtotal = $317,688 )
2016	2016	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	001	7	1/11/2016	COMPETING CONTINUATION	$317,688
2016	2014	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 Ashley Ave	CHARLESTON	SC	294258908	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	6	1/6/2016	NON-COMPETING CONTINUATION	$0
														Subtotal = $317,688

Issue Date FY: 2014 ( Subtotal = $355,596 )
2014	2014	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	6	3/7/2014	NON-COMPETING CONTINUATION	$355,596
														Subtotal = $355,596

Issue Date FY: 2013 ( Subtotal = $337,934 )
2013	2013	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	001	5	5/15/2013	NON-COMPETING CONTINUATION	$17,787
2013	2013	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	5	3/28/2013	NON-COMPETING CONTINUATION	$320,147
														Subtotal = $337,934

Issue Date FY: 2012 ( Subtotal = $355,831 )
2012	2012	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	4	3/14/2012	NON-COMPETING CONTINUATION	$355,831
														Subtotal = $355,831

Issue Date FY: 2011 ( Subtotal = $355,933 )
2011	2011	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	001	3	6/2/2011	NON-COMPETING CONTINUATION	$25,004
2011	2011	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	000	3	3/23/2011	NON-COMPETING CONTINUATION	$330,929
														Subtotal = $355,933

Issue Date FY: 2010 ( Subtotal = $373,951 )
2010	2010	MEDICAL UNIVERSITY OF SOUTH CAROLINA	19 HAGOOD AVE, SUITE 608	CHARLESTON	SC	29403	CHARLESTON	USA	Research Related to Deafness and Communication Disorders	001	2	8/18/2010	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$339,243
2010	2010	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	000	1	2/26/2010	NEW	$381,355
2010	2010	UNIVERSITY OF MICHIGAN	3003 S STATE ST 3089 WOLVERINE	ANN ARBOR	MI	48109	WASHTENAW	USA	Research Related to Deafness and Communication Disorders	002	1	8/18/2010	NEW	-$346,647
														Subtotal = $373,951

Grand Total All Awards = $5,126,056

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Molecular mechanism in noise-induced hearing loss

Award Number: R01DC009222

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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