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.
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.
|Hill, Kayla; Yuan, Hu; Wang, Xianren et al. (2016) Noise-Induced Loss of Hair Cells and Cochlear Synaptopathy Are Mediated by the Activation of AMPK. J Neurosci 36:7497-510|
|Chen, Jun; Hill, Kayla; Sha, Su-Hua (2016) Inhibitors of Histone Deacetylases Attenuate Noise-Induced Hearing Loss. J Assoc Res Otolaryngol 17:289-302|
|Chen, Jun; Yuan, Hu; Talaska, Andra E et al. (2015) Increased Sensitivity to Noise-Induced Hearing Loss by Blockade of Endogenous PI3K/Akt Signaling. J Assoc Res Otolaryngol 16:347-56|
|Yuan, Hu; Wang, Xianren; Hill, Kayla et al. (2015) Autophagy attenuates noise-induced hearing loss by reducing oxidative stress. Antioxid Redox Signal 22:1308-24|
|Han, Yu; Wang, Xianren; Chen, Jun et al. (2015) Noise-induced cochlear F-actin depolymerization is mediated via ROCK2/p-ERM signaling. J Neurochem 133:617-28|
|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, 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|
|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|
|Chen, Fu-Quan; Zheng, Hong-Wei; Hill, Kayla et al. (2012) Traumatic noise activates Rho-family GTPases through transient cellular energy depletion. J Neurosci 32:12421-30|