The prevalence of disabling hearing loss rose globally from 42 to 466 million cases since 1985, now comprising approximately 6-8% of the world’s population. While congenital deafness, left untreated, leads to poor educational achievements and social isolation, with increasing age, hearing impairment is associated with accelerated cognitive decline and has been linked to an increased risk of dementia. The current COVID-19 pandemic has complicated the lives of the hearing impaired even further.

 

A major goal in auditory science is to understand how the cells of the inner ear develop to provide the exquisite precision of hearing. The organ of Corti, which houses the sensory cells of the inner ear, develops from sensory epithelium derived from ectoderm. Together with innervation of the sensory spiral ganglion cells, the auditory system collects sounds and transforms their mechanical forces into an electrical signal that functions throughout the lifetime. At a molecular level, the interactions of DNA, RNA, and proteins of the auditory system orchestrate a remarkable feat that is summarized in our ability to hear (reviewed in Doetzlhofer & Avraham, Semin Cell Dev Biol 2016). The challenge in auditory science is to determine which and how a pathogenic variant in a gene or regulatory element can cause the entire hearing system to fail.

 

The Avraham team is asking the questions: (1) What are the genes that lead to hearing loss and how are they involved in the normal function of the inner ear? (2) How does the regulation of gene expression govern the pathways that determine inner ear function and how do alterations in regulation, on a genetic and epigenetic level, contribute to the pathology of deafness?

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Figure from Dror AA & Avraham KB. Neuron, 2010