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Scientists Identify Proteins Crucial To Loss of Hearing


Hearing loss is quite a common phenomenon; close to 40 million Americans suffer from it. Till date, there is no known way to reverse the condition as the auditory hair cells, which sense sound and relay that information to the brain do not regenerate. However, in a new study led by the scientists at the University Of Maryland School Of Medicine (UM SOM), the results of which appeared in the latest issue of the journal Nature Communications, something crucial has been discovered. They have found a key clue to how these hair cells develop. The researchers have identified a new role for a particular group of proteins, called RFX transcription factors, in the development and survival of the auditory hair cells.

Ronna P. Hertzano, MD, PhD, Assistant Professor of Otorhinolaryngology-Head & Neck Surgery at the UM SOM and the principal investigator of the study said that this discovery is crucial as it opens up new avenues, not only for understanding the genetics of hearing, but also, eventually for treating deafness. The research was carried out in collaboration with scientists at several institutions, among them Ran Elkon, PhD, an Assistant Professor and computational biologist at the Sackler School of Medicine at Tel Aviv University in Israel.

For the study, mice whose auditory hair cells glow with a green fluorescent protein were used by the researchers as it lets the cells to be identified from other kind of cells. Next generation sequencing was later applied by them “ it is a state-of-the-art method to rapidly measure gene expression – to sequence and quantify the thousands of genes that are expressed in hair cells, in comparison with other cells in the ear. The researchers were particularly interested in searching for key regulators of genes for hair cells as they could be key in helping researchers eventually develop techniques to regenerate hair cells. The RFX transcription factors were the key regulator identified by them.

To further their study, the researchers then studied mice that were genetically modified so that two of the RFX transcription factors were lacking in their hair cells. Initially the hair cells in the mice developed normally, but then died quickly, leading to rapid hearing loss. In just three months, the mice were totally deaf.

Hertzano is of the opinion that the genes are likely to work in a similar fashion in humans. She added that it might be possible to use our increased understanding of RFX transcription factor to treat hearing loss, by either protecting hair cells from death or fostering their growth. Next they are on the lookout to identify other genes that have an important role in hair cell function.

This paper appeared in conjunction with another paper published in Nature Communications, by Matthew W. Kelley, PhD, a neuroscientist at the National Institute on Deafness and Other Communication Disorders. Kelley and his team also used mice with fluorescent markers in different cells of the ear followed by next generation sequencing. They didn't go for analyzing groups of cells; on the other hand they performed a comprehensive analysis of the genes that are expressed in the different cells at a single cell resolution. The study is a pioneer in the ear field and can be instrumental in resolving the molecular aspects of the cellular complexity of the inner ear.

Hertzano interest in understanding the genetics of hearing started when she was an MD-PhD student at Tel Aviv University. She has then pursued residency training at the UM SOM Department of Otorhinolaryngology, where she now works as a scientist and a surgeon. Her practice is focused on diseases of the ear and hearing restoration.

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