# Molecular mechanism in noise-induced hearing loss

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $339,665

## Abstract

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.

## Key facts

- **NIH application ID:** 10444429
- **Project number:** 2R01DC009222-12A1
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Su-Hua Sha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $339,665
- **Award type:** 2
- **Project period:** 2010-04-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444429

## Citation

> US National Institutes of Health, RePORTER application 10444429, Molecular mechanism in noise-induced hearing loss (2R01DC009222-12A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10444429. Licensed CC0.

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