Miyoshi Lab

The central goal of our lab is to elucidate how the motor activity of MYO7A is regulated in stereocilia. We recently demonstrated that MYO7A likely traffics as a dimer, consistent with previous studies on cargo-mediated dimerization of this myosin. However, it remains unknown what factors release MYO7A from its autoinhibitory conformation and trigger its dimerization (or possibly multimerization) in hair cells. We are currently investigating physiological activators of MYO7A trafficking, which may serve as key molecules for regenerating stereocilia with functional MET machinery.

We are also expanding our imaging efforts to include MYO15A, the stereocilia elongator. This myosin resembles MYO7A in its motor domain, whose kinetic properties are compatible with processive movement as a dimer along actin filaments, as well as in its overall domain architecture. However, MYO7A and MYO15A interact with distinct cargo proteins and play different roles in stereocilia development. We are examining how MYO15A reaches stereocilia tips and promotes actin filament elongation.

Finally, we are advancing our STELLA workflow to achieve higher spatial resolution and sensitivity by leveraging cutting-edge microscopy platforms. Tracking of myosin molecules is also being enhanced through artificial intelligence (AI)-based methodologies, in collaboration with the SIU School of Computing and Engineering. These advances will enable more detailed analyses of myosin dynamics in stereocilia and provide a technical foundation for detecting aberrant kinetics of myosin and cargo variants found in patients with hearing loss.