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Hearing loss is a common sensory disorder affecting approximately 17% of American adults. The cause of hearing loss range from inherited genetic defects to noise-induced trauma. Auditory neuropathy due to spiral ganglion neuron (SGN) loss is of particular concern. No treatment is available for SGN loss, but stem cell replacement therapy has shown great promise for treating hearing loss. Expression of key genes in pluripotent stem cells may facilitate differentiation during SGN regeneration. We employ a variety of techniques including super-resolution imaging and massively parallelized sequencing methods to study regeneration of SGNs.

Using an inner ear stem cell, genome wide epigenetic changes were observed during neuronal differentiation. We identified chromatin readers, writers, erasers and remodelers in differentiating inner ear stem cells.  We are interested in the chromodomain helicase DNA binding protein 7 (Chd7), an ATP dependent nucleosome repositioning protein. Mutations in human Chd7 causes CHARGE syndrome. Among the constellation of clinical features observed in patients with CHARGE is hearing loss. The inner ear abnormalities observed in animals lacking Chd7 include improper development of SGNs. Using a combination of inner ear stem cell lines and mouse models, we are investigating the molecular underpinnings of Chd7 function during SGN development and regeneration.