The overall goal is to elucidate the mechanisms that regulate the formation and maintenance of the stereociliary bundle of cochlear hair cells, and the defects in this process that cause deafness. We propose here to investigate the normal functions and the pathophysiological changes associated with Fam65b mutation that cause deafness. Based on our preliminary data, we hypothesize that Fam65b is critical for the structural organization of stereociliary bundle of cochlear hair cells. To test our hypothesis, we will: i) continue our characterization of Fam65b(-/-) hair cells; ii) characterize Fam65b functiona domains; iii) look for interaction partners for Fam65b that functionally cooperate in hair bundle morphogenesis. Our preliminary data show the feasibility of our approach. We anticipate that our studies will shed new insights into the molecular machinery that shapes stereocilia and determines its properties. Quite possibly, our findings may link several deafness-related genes into a common molecular pathway and provide new leads for the development of therapeutic approaches for the treatment of some forms of the disease.
Hearing loss is a major health problem that significantly affects the life quality of affected individuals. Mutations in FAM65B have been liked to deafness in human. For this project we will investigate the normal function of Fam65b and the pathophysiological changes associated with Fam65b mutation that causes deafness. We anticipate providing new leads for the development of therapeutic approaches for the treatment of some forms of hearing loss.
| Liu, Chang; Luo, Na; Tung, Chun-Yu et al. (2018) GRXCR2 Regulates Taperin Localization Critical for Stereocilia Morphology and Hearing. Cell Rep 25:1268-1280.e4 |
| Zhao, Bo; Wu, Zizhen; Müller, Ulrich (2016) Murine Fam65b forms ring-like structures at the base of stereocilia critical for mechanosensory hair cell function. Elife 5: |
