Research 

Far from being an inert divider between cells, the lipid bilayer forms an active environment harboring and regulating the functions of the membrane proteins contained within them to regulate many essential cell functions. The physical properties of the lipid bilayer are critical for the proper function of a variety of ion channels, especially in mechanosensitive ion channels. Mechanotransduction is a key step in many sensory processes, including touch, pain, osmoregulation, balance, and hearing. Our lab focuses on the importance of the cell membrane in auditory hair cells, the primary sensory cells responsible for converting mechanical stimulation into electrical output. Auditory mechanotransduction occurs in the hair bundles, composed of rows of stereocilia, on the apical surface of the auditory hair cells. Deflections of the hair bundles open MET channels that reside at the tops of the shorter stereocilia. A major focus of our lab is understanding the cellular and molecular mechanisms underlying the stereocilia membrane regulation in the cochlea, its functional relevance to auditory hair cell mechanotransduction, a site for where multiple human genetic mutations occur, and a target of noise and age induced hearing loss.

Some specific research areas in the lab includes:

• Investigate the biochemical pathways by which the mechanotransduction channel is regulating the stereocilia membrane as well as the biophysical consequence of the stereocilia membrane regulation.

• Investigate the molecular mechanisms that regulate lipid metabolism and membrane homeostasis in the auditory system and characterize how disruption of these critical components leads to hearing loss.

• Understand how the stereocilia membrane influences the mechanical coupling between components of hair cell mechanotransduction complex at the molecular level and investigate the pathways of force transmission to the channel complex.

• Characterize the peripheral auditory membrane by in vivo real time monitoring.

We have now developed fluorescence-based live imaging techniques to directly assess the membrane properties of individual stereocilium (~300-400 nm in diameter) including a novel viscosity sensitive 'molecular rotor', BODIPY 1c, based on fluorescence lifetime imaging, for the first time in the inner ear. Coupled with electrophysiological and high/super-resolution imaging techniques such a lightning confocal imaging and STED imaging, we will use multifaceted tool sets in rodents to address these research areas.