Non-coding regulatory elements in the development of cochlear sensory hair cells

Various forms of congenital and acquired hearing deficiency affect millions of people worldwide. One of the major causes of hearing loss is underdevelopment or degeneration of sensory hair cells of the cochlea in the inner ear, and understanding the molecular mechanisms of hair cells formation and functioning is advancing the auditory research community towards successful hearing restoration.

The mouse model is highly instrumental in hearing research due to the morphological, developmental and genetic conservation between mouse and human auditory systems and allows genetic manipulation and disease modeling. Multiple genetic studies have unraveled key genes and pathways playing a role in cochlear hair cell development, but epigenetic regulation of this process is a relatively new research focus. The latest findings in the field have demonstrated the importance of non-coding regulatory elements such as enhancers in both natural development of hair cells and their potential regeneration in case of disease and/or damage.

The major goal of our research is to identify potential causal relationships between non-coding genetic variants and hearing loss phenotypes, that would enable epigenetic therapy to restore hearing. Currently, we are using the murine model to further characterize and functionally validate multiple enhancers proposed to play a role in hair cell development, by means of high-throughput epigenomics. Down the road, these enhancers will be mapped to their potential human homologs and screened for potential previously unexplained deafness-associated variants. We are working to introduce a variety of cutting-edge methods, such as single-cell techniques and in vitro cochlear organoids, into our experimental toolkit.