Hair Cell

University of Maryland Medical Center (UMMC) researchers conducted a study which determined the role that a critical protein plays in the development of hair cells vital to hearing. Hair cells are the specialized inner-ear cells responsible for amplifying sounds that come into the ear or the transduction of sound-evoked mechanical vibrations into electrical signals that are then relayed to the brain. Ronna Hertzano, MD, PhD, Associate Professor in the Department of Otorhinolaryngology Head and Neck Surgery at UMSOM, in conjunction with other researchers, demonstrated that the protein, called GFI1, functions to repress neuronal gene expression in the developing inner ear hair cells.

Dr. Hertzano’s research uses cell type-specific approaches to (1) define the key regulatory events that lead to cell type-specific differentiation. Specifically, identification and characterization of transcriptional cascades that lead to hair cell terminal differentiation and survival as a crucial step in developing regenerative treatments for hearing loss; and (2) defining the molecular events as a result of acquired and noise-induced hearing loss to develop novel approaches for prevention and treatment of these problems. The team uses cell type-specific genomic approaches in mice and zebrafish, followed by validation using genetically engineered animal models and classic experimental and developmental biology techniques.

To conduct her latest study, funded by the National Institute on Deafness and Other Communication Disorders (NIDCD)/National Institutes of Health (NIH) and by the Binational Scientific Foundation (BSF), Dr. Hertzano and her team utilized cutting-edge methods to study gene expression in the hair cells of genetically modified newborn mice that did not produce GFI1.

When the hair cells of the inner ear do not develop properly or are damaged by environmental stresses like loud noise, hearing function loss develops. The study proposes a dual mechanism for GFI1 in promoting hair cell development, consisting of repression of neuronal-associated genes, as well as activation of hair cell-specific genes required for normal functional maturation.

The study was published in the journal Development, and was conducted by physician-scientists and researchers at the University of Maryland Department of Otorhinolaryngology Head and Neck Surgery and the UMSOM Institute for Genome Sciences (IGS), in collaboration with researchers at the Sackler School of Medicine at Tel Aviv University in Israel.

“Our findings explain why GFI1 is critical to enable embryonic cells to progress into functioning adult hair cells,” said Dr. Hertzano. “These data also explain the importance of GFI1 in experimental protocols to regenerate hair cells from stem cells. These regenerative methods have the potential of being used for patients who experience hearing loss due to age or environmental factors.”

Dr. Hertzano first became interested in GFI1 while completing her M.D., Ph.D. at Tel Aviv University. As part of her dissertation, she discovered that the hearing loss resulting from mutations in another protein (POU4F3) appeared to largely result from a loss of GFI1 in the hair cells. Since then, she conducts studies to discover the role of GFI1 and other proteins in hearing. Other research groups in the field are now testing these proteins to determine whether they can be combined to regenerate lost hair cells and restore hearing.

“Hearing research has been going through a Renaissance period, not only from advances in genomics and methodology, but also thanks to its uniquely collaborative nature among researchers,” said Dr. Hertzano.

Call 410-328-5828 to refer a hearing loss patient.  For more information about ENT research at UMMC, see the Otolaryngology