Research Area Affiliations
Sensory hair cells, the sensory receptors of the auditory system, must convey a wide range of sound intensities (from a whisper to a thunderclap) to the central nervous system 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.
Dr. Sheets’ research focuses on the formation and maintenance of hair-cell synapses. She studies the cellular processes that bring about hair-cell synapse loss following sound overexposure using zebrafish as a model for human hearing and deafness. Additionally, Dr. Sheets takes advantage of the zebrafish's extensive regenerative capacity to investigate how zebrafish regenerate hair-cell innervating nerve fibers and synaptic connections following damaging noise exposures. She anticipates that uncovering the cellular mechanisms that mediate noise-induced synapse loss and recovery in zebrafish will lead to the development of therapies to protect or replace damaged hair-cell synaptic contacts in humans.
Excessive activation of ionotropic glutamate receptors induces apoptotic hair-cell death independent of afferent and efferent innervation. Sheets L. Sci Rep. 2017 Jan 23. 7:41102. doi: 10.1038/srep41102.
Synaptic ribbons require ribeye for electron density, proper synaptic localization, and recruitment of calcium channels. Lv C, Stewart WJ, Akanyeti O, Frederick C, Zhu J, Santos-Sacchi J, Sheets L, Liao JC, Zenisek D. Cell Rep. 2016 Jun 21. 15(12):2784–95. doi: 10.1016/j.celrep.2016.05.045.
Characterization of Ribeye subunits in zebrafish hair cells reveals that exogenous Ribeye B-domain and CtBP1 localize to the basal ends of synaptic ribbons. Sheets L, Hagen MW, Nicolson T. PLoS One. 2014 Sep 10. 9(9):e107256. doi: 10.1371/journal.pone.0107256.
Presynaptic CaV1.3 channels regulate synaptic ribbon size and are required for synaptic maintenance in sensory hair cells. Sheets L, Kindt KS, Nicolson T. Journal of Neuroscience. 2012 Nov 28. 32(48):17211–17224
Ribeye is required for presynaptic CaV1.3a channel localization and afferent innervation of sensory hair cells. Sheets L, Trapani JG, Mo W, Obholzer N, Nicolson T. Development. 2011 Apr. 138(7):1309–19.
Zebrafish melanophilin facilitates melanosome dispersion by suppressing dynein motility. Sheets L, Ransom DG, Mellgren EM, Johnson SL, Schnapp BJ. Current Biology. 2007 Oct 23. 17(20):1721–34.
View a complete list of publications on pubmed.gov »