Noise-induced hearing loss is a major cause of acquired hearing deficits and one of the most frequent work-related disabilities in industrialized countries. The long term goal of this research is to understand the molecular mechanisms leading to noise-induced hearing loss. Based on exciting preliminary results on a signaling cascade initiated by energy depletion after noise exposure, the hypothesis is presented that transient energy depletion is an initial key factor in noise trauma. Transient energy depletion activates small GTPase pathways, which, in turn, lead to the destruction of F-actin in outer hair cells. Transient energy depletion also initiates mitochondria-mediated cell death, and blocks mTOR signaling pathways which normally serve as survival functions. In addition to the in-vivo studies, we are introducing a novel in-vitro model of energy depletion in an inner ear cell line to study specific aspects of the molecular pathways suspected in noise-induced hearing loss. The results of this project will lead to new insight into mechanisms of noise trauma. In addition, the results of this project may direct the design of novel interventions for the prevention of noise-induced hearing loss benefiting the quality of life of individuals and reducing health care costs.

Public Health Relevance

Noise-induced hearing loss is a major cause of acquired hearing deficits and one of the most frequent work-related disabilities in industrialized countries. The results of this project will lead to new insight into mechanisms of noise trauma. Thereby, the results of this project may direct the design of novel interventions for the prevention of noise- induced hearing loss benefiting the quality of life of individuals and reducing health care costs.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01DC009222-06
Application #
8642623
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Pathology
Type
Schools of Medicine
DUNS #
City
Charleston
State
SC
Country
United States
Zip Code
29403
Zheng, H-W; Chen, J; Sha, S-H (2014) Receptor-interacting protein kinases modulate noise-induced sensory hair cell death. Cell Death Dis 5:e1262
Chen, Fu-Quan; Zheng, Hong-Wei; Schacht, Jochen et al. (2013) Mitochondrial peroxiredoxin 3 regulates sensory cell survival in the cochlea. PLoS One 8:e61999
Oishi, Naoki; Chen, Jun; Zheng, Hong-Wei et al. (2013) Tumor necrosis factor-alpha-mutant mice exhibit high frequency hearing loss. J Assoc Res Otolaryngol 14:801-11
Oishi, Naoki; Chen, Fu-Quan; Zheng, Hong-Wei et al. (2013) Intra-tympanic delivery of short interfering RNA into the adult mouse cochlea. Hear Res 296:36-41