Deafness Project
Advancing therapies through functional characterization of hearing loss-associated genes
Research summary
Hearing loss is a very common sensory disorder that severely affects human quality of life. In order to develop effective therapeutic strategies for deafness, it is critical to understand the mechanisms regulating its onset. Our aim is to discover novel genes associated with deafness. In particular, we are focused on identifying genes responsible for age-related hearing loss (ARHL). While genes responsible for congenital hearing loss have been identified, genes associated with ARHL, which affects a far greater number of people, have not.
Many types of hearing loss are associated with loss of outer hair cells (OHCs), which are responsible for the amplification of sound. Thus, we study the development and maintenance of OHCs. OHCs form a characteristic V-shaped stereocilia architecture. However, the genetic and molecular mechanisms involved in OHC development and death are poorly understood. To better understand OHCs and ARHL, we are:
- 1) Identifying genes causing and modifying ARHL in mouse models using forward genetics approaches.
- 2) Functionally analyzing proteins involved in the development of the OHC V-shaped stereocilia architecture.
- 3) Investigating the molecular mechanisms involved in OHC deaths using an OHC-specific depletion system.
Selected Publications
- Yasuda SP et al. (2022)“Two loci contribute to age-related hearing loss resistance in the Japanese wild-derived inbred MSM/Ms mice” Biomedicines 10: 2221
- Seki et al. (2021) “Myosin VI haploinsufficiency reduced hearing ability in mice.” Neuroscience. 478:100-111.
- Yasuda SP et al. (2020) “c.753A>G genome editing of a Cdh23ahl allele delays age-related hearing loss and degeneration of cochlear hair cells in C57BL/6J mice.” Hear. Res. 389: 107926.
- Matsuoka K et al. (2019) “OHC-TRECK: A novel system using a mouse model for investigation of the molecular mechanisms associated with outer hair cell death in the inner ear.” Sci. Rep. 9:5285.
- Seki Y, et al. (2017) “A novel splice site mutation of myosin VI in mice leads to stereociliary fusion caused by disruption of actin networks in the apical region of inner ear hair cells.” PLoS One 12, e0183477.
- Miyasaka Y, et al. (2016) “Heterozygous mutation of Ush1g/Sans in mice causes early-onset progressive hearing loss, which is recovered by reconstituting the strain-specific mutation in Cdh23.” Hum. Mol. Genet. 25: 2045-2059.
- Kikkawa Y and Miyasaka Y. (2016) “Genetic modifiers of hearing loss in mice: The case of phenotypic modification in homozygous Cdh23ahl age-related hearing loss.” Monogr. Hum. Genet. 20: 97–109.