Graduate Training in Neuroscience
University of Washington
Research Professor, Otolaryngology/Head and Neck Surgery
Mechanosensory transduction via hair cells is necessary for auditory and vestibular perception and is central to survival and communication in many species. Hair cells are damaged by ototoxic drugs, noise, microbial infections, and the normal aging process. Mammals are unable to regenerate hair cells, so the loss of hair cells leads to profound sensory deficits. By contrast, avian species produce vestibular hair cells continually throughout their lives. In addition, they regenerate auditory and vestibular hair cells in response to experimental damage, fully restoring hearing and balance function.
In birds, two cellular processes lead to the restoration of hair cells. The first process, called direct transdifferentiation, involves the phenotypic conversion of non-sensory supporting cells into hair cells. The second involves mitosis of supporting cells and differentiation of progeny into hair cells. The Stone lab examines the molecular signaling cascades involved in these two processes. Our lab is currently focusing on the interchange between proneural transcription factors and Notch receptor signaling in guiding chicken supporting cells to undergo either direct transdifferentiation or cell division. Our lab uses genetic profiling, cell and organ culture, genetic transfection, cell transplantation, and confocal microscopy to test hypotheses about the role of specific molecules in regulating hair cell regeneration. Knowledge gained in studies on chickens will be applied in similar experiments in mice in order to stimulate hair cell regeneration in mammals.