Lavinia Sheets, Ph.D.

Assistant Professor
Otolaryngology

Neurosciences Program
Developmental, Regenerative and Stem Cell Biology Program
Molecular Cell Biology Program

  • 314-273-1857

  • sheetsl@wustl.edu

  • Defining pathological changes in noise-exposed sensory hair cells and identifying pathways that promote repair

Research Abstract:

Hair cells are the sensory receptors of sound, motion, and spatial orientation. Overexposure to loud sounds initiates a series of molecular events in cochlear hair cells that contribute to various hair-cell pathologies: intense noise-exposures induce hair-cell death while moderate-noise exposures contribute to progressive hair-cell synapse loss,
postsynaptic retraction, and cochlear nerve degeneration. Our research interests are to understand how specific pathological changes occur in hair cells overexposed to noise by defining the cellular mechanisms driving hair-cell synapse loss and hair-cell death, as well as identifying pathways that promote repair.

My lab address these questions using zebrafish as a model for hearing and deafness. Zebrafish afford a powerful model system to uncover the cellular mechanisms of noiseinduced synaptopathy and hair-cell loss. Zebrafish sensory hair cells are homologous to mammalian hair cells, and there is a high conservation of zebrafish deafness gene function compared with humans. In contrast to other vertebrate model organisms, zebrafish hair cells are optically accessible in whole larvae within the ear and the lateral line organ-a sensory organ used to detect the movement of water. Additionally, zebrafish hair cells are amenable to pharmacological manipulation, allowing for large scale drug screening and subsequent examination of hair-cell morphology and function. Moreover, as zebrafish have an extensive capacity for regeneration of complex tissues, including hair cells and afferent neurons, they can be used to identify molecular pathways that promote synapse regeneration following hair-cell damage.

Selected Publications:

Sheets L, Trapani JG, Mo W, Obholzer N, Nicolson T. Ribeye is required for presynaptic CaV1.3a channel
localization and afferent innervation of sensory hair cells. Development 2011 Apr;138(7):1309-19. Cover Article
Recommended by Faculty of 1000

Sheets L, Kindt KS, Nicolson T. Presynaptic CaV1.3 channels regulate synaptic ribbon size and are required
for synaptic maintenance in sensory hair cells. Journal of Neuroscience, 2012 Nov 28, 32(48):17211-17224.

Sheets L, Hagen MW, Nicolson T. Characterization of Ribeye subunits in zebrafish hair cells reveals that
exogenous Ribeye B-domain and CtBP1 localize to the basal ends of synaptic ribbons. PLOS One, 2014 Sep
10; 9(9):e107256.

Lv C, Stewart WJ, Akanyeti O, Frederick C, Zhu J, Santos-Sacchi J, Sheets L, Liao JC, and Zenisek D.
Synaptic ribbons require Ribeye for electron density, synaptic localization and proximity to calcium channels,
but not for vesicle recruitment and neurotransmitter release. Cell Reports, 2016, Jun 21;15(12):2784-95.

Sheets L. Excessive activation of ionotropic glutamate receptors induces apoptotic hair-cell death
independent of afferent and efferent innervation. Scientific Reports, 2017 Jan 23;7:41102.

Last Updated: 1/19/2018 11:17:30 AM

Back To Top

Follow us: