Thursday, October 15, 2015
Almost 40 million Americans suffer from hearing loss. Right now, there is no way to reverse this condition, largely because auditory hair cells, which sense sound and relay that information to the brain, do not regenerate.
A new study led by scientists at the University of Maryland School of Medicine (UM SOM) has found a key clue to how these hair cells develop. The current study identified a new role for a particular group of proteins, known as RFX transcription factors, in the development and survival of the hair cells.
“This discovery opens up new avenues, not only for understanding the genetics of hearing, but also, eventually for treating deafness,” said the principal investigator, Ronna P. Hertzano, MD, PhD , Assistant Professor of Otorhinolaryngology-Head & Neck Surgery at the UM SOM.
The study appeared in the latest issue of the journal Nature Communications. The work was done 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.
Hertzano and her colleagues used mice whose auditory hair cells glow with a green fluorescent protein, allowing the cells to be identified from other kinds of cells. They then used next generation sequencing – 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. As they generated this catalogue of genes, they were searching for key regulators of genes for hair cells. Such regulators could help researchers eventually develop techniques to regenerate hair cells. The key regulator they identified were the RFX transcription factors.
The scientists then moved on to study mice which had been genetically altered so that their hair cells lacked two of the RFX transcription factors. In these mice, hair cells initially developed normally, but then died quickly, leading to rapid hearing loss. By three months of age, the mice were profoundly deaf.
Although the experiments were done in mice, Hertzano says that it is likely that these genes work similarly in humans. Eventually, she says, 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. In addition, she and her colleagues think that they will be able to identify other genes that have an important role in hair cell function.
Hertzano first got interested in the genetics of hearing as an MD-PhD student at Tel Aviv University, and then pursued residency training at the UM SOM Department of Otorhinolaryngology, where she now works as a scientist and a surgeon whose practice is focused on diseases of the ear and hearing restoration.
The current 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. Rather than analyzing groups of cells, they performed a comprehensive analysis of the genes that are expressed in the different cells at a single cell resolution. Their study is the first of its kind in the ear field and helps resolved the molecular aspects of the cellular complexity of the inner ear.
“Dr. Hertzano’s discovery opens up new possibilities for those who suffer from hearing loss,” said UM SOM Dean E. Albert Reece, MD, PhD, MBA , who is also Vice President of Medical Affairs, the University of Maryland and the John Z. and Akiko Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. “This is still very early in the process, but I know that Dr. Hertzano and her colleagues have uncovered an important piece of the puzzle, one that will yield clinical benefit in the years to come.”
The University of Maryland School of Medicine was chartered in 1807 and is the first public medical school in the United States and continues today as an innovative leader in accelerating innovation and discovery in medicine. The School of Medicine is the founding school of the University of Maryland and is an integral part of the 11-campus University System of Maryland. Located on the University of Maryland’s Baltimore campus, the School of Medicine works closely with the University of Maryland Medical Center and Medical System to provide a research-intensive, academic and clinically based education. With 43 academic departments, centers and institutes and a faculty of more than 3,000 physicians and research scientists plus more than $400 million in extramural funding, the School is regarded as one of the leading biomedical research institutions in the U.S. with top-tier faculty and programs in cancer, brain science, surgery and transplantation, trauma and emergency medicine, vaccine development and human genomics, among other centers of excellence. The School is not only concerned with the health of the citizens of Maryland and the nation, but also has a global presence, with research and treatment facilities in more than 35 countries around the world. http://medschool.umaryland.edu/