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William F. Sewell, Ph.D.

Professor, Department of Otology and Laryngology

wfs@epl.meei.harvard.edu

Research is centered on synaptic transmission and the chemistry and pharmacology in the inner ear. Current projects include: (1) understanding how glutamate receptor trafficking at the synapse between the sensory cell of the ear, the hair cell, and the auditory neuron regulates sensitivity of the ear to sound. (2) understanding the molecular structure of the synaptic ribbon, an intracellular presynaptic organelle important for neurotransmitter release from the sensory cell; we have taken a proteomics approach to identify the molecular components of the ribbon and a pharmacological approach to identify the specific role of each of the proteins in synaptic transmission. (3) inner ear drug delivery: we are working with colleagues at Draper Laboratory to develop a drug delivery system suitable for use in the human inner ear. (4) Molecular mechanisms of acoustic trauma and ototoxic drugs; we have identified a transcription factor, PLZF, whose activation can protect the cochlea from acoustic injury. 

 
Recent Publications:
Chen, Z., Kujawa, S. G., Sewell, W. F. Auditory sensitivity regulation via rapid changes in expression of surface AMPA receptors. Nature Neurosci. 10:1238-40. 2007.
 
Wang, L., Sewell, W.F., Kim, S., Shin, J., MacRae, C., Zon, L., Seidman, J.G., and Seidman, C. Eya4 regulation of Na/K-ATPase is required for sensory system development in zebrafish. Development 135:3425-34, 2008.
 
Leary Swan EE, Peppi M, Chen Z, Green KM, Evans JE McKenna MJ, Mescher MJ, Kujawa SG, Sewell WF. Proteomics Analysis of Perilymph and Cerebrospinal Fluid in Mouse. The Laryngoscope. May; 119 (5): 953-8, 2009.
 
Chen Z, Peppi M, Kujawa SG, Sewell WF. Regulated expression of surface AMPA receptors reduces excitotoxicity in auditory neurons. J Neurophysiol. 102(2): 1152-9, 2009.
 
Leary PararasEE, ChenZ, FieringJ, MescherMJ, KimES, McKennaMJ, KujawaSG, BorensteinJT, SewellWF, Kinetics of Reciprocating Drug Delivery to the Inner Ear. J Controlled Release 152: 270-7, 2011.
 
Peppi M, Kujawa SG, and Sewell WF. A corticosteroid-responsive transcription factor, PLZF, mediates protection of the cochlea from acoustic trauma. J. Neuroscience. 31: 735-41, 2011.