Research Projects

Sensory hair cells—the sensory receptors of the auditory system—must convey a wide range of sound intensities (from a whisper to a thunderclap) and do so both reliably and inexhaustibly. This is accomplished by exquisitely sensitive synaptic connections between hair cells and nerve fibers that carry sensory information to the brain. The sensitivity of hair-cell synaptic connections comes at a price—they are vulnerable to damage when exposed to intense noise. Recent research indicates prolonged exposure to moderately loud noise, such as a rock concert or a stadium football game, damages hair-cell synaptic connections, resulting in hair-cell synapse loss and permanent deficits in auditory acuity. 

Zebrafish are a well-established model for human hearing and deafness and provide an advantageous system to investigate mechanisms of noise-induced hair-cell damage. The zebrafish lateral-line organ—a sensory organ used to detect the movement of water—contains superficially localized hair cells that are relatively easy to manipulate pharmacologically or genetically, and are optically accessible in whole larval fish. We can thereby manipulate cellular pathways in hair cells and examine progressive hair-cell damage in a live, intact preparation.  In addition, the Sheets lab takes advantage of the zebrafish’s ability to regenerate complex tissues following damage, including hair-cells and their innervating nerve fibers.

The Sheets Lab’s research projects are:

- Defining the cellular pathways that bring about hair-cell synapse loss and hair cell death following damaging noise exposures.

- Identifying biological pathways that promote nerve regeneration and hair-cell reinnervation with the goal of providing information toward clinical regenerative therapies.

- Identifying novel protectants against cisplatin-induced neurotoxicity with the goal of protecting auditory nerve fibers from damage during cisplatin-based chemotherapy.