[return to list] 
Jeffrey  R.  Holt
Degree(s): Ph.D.
Graduate School: University of Rochester
Primary Appointment: Associate Professor of Neuroscience
Research Interests:
Sensory signaling in hair cells of the auditory and vestibular systems.

Email Address: jeffholt@virginia.edu
Biomedical Sciences Graduate Program(s)
  • Neuroscience
  • Structural, Computational Biology and Biophysics
  • Molecular Cell and Developmental Biology
    • Research Description

    Sensory hair cells of the inner ear can detect movements of their mechano-sensitive organelles as small a few nanometers (about one millionth of an inch). In the auditory system this exquisite sensitivity can initiate a sensory signal which is transmitted to the brain where the faint pizzicato of a classical violin may be perceived. Remarkably, hair cells are also sensitive to stimuli with amplitudes over a thousand times greater, and thus are able to signal the booming cannons of Tchaikovsky's 1812 Overture as well.

    We are actively engaged in research that aims to identify the molecules that allow the mechanical information carried by sound, and head movements in the vestibular system, to be converted into electrical responses. We have recently identified a couple of candidate proteins that we believe are key components of the mechano-sensitive apparatus in hair cells. One of them, known as myosin 1c, is a motor protein that controls the sensitivity of hair cells and allows the cells to respond to a broad range of stimulus amplitudes. Another, known as KCNQ4, causes deafness when mutated and is important for maintaining the hair cell resting potential and modulating the sensory signal as it propogates from the mechanosensory hair bundle to the afferent synapse.

    The goal of our research is to identify the genes and proteins necessary for normal hearing and balance function and to understand why mutations in those genes cause hereditary inner ear dysfunction. Our general strategy is to use molecular and genetic techniques to manipulate gene and protein activity and electrophysiology to assay for alterations in hair cell function. The combined approach has proven extremely powerful and has shed new light on inner function and dysfunction. Our long term goal is to apply what we learn from these experiments to help design rational gene therapy approaches to treat deafness and balance disorders which together afflict over 30 million Americans, and greater than 250 million people world-wide.

    Selected Publications
  • Holt JR, Stauffer EA, Abraham D, Géléoc GS. Dominant-negative inhibition of M-like potassium conductances in hair cells of the mouse inner ear. J Neurosci. 2007 Aug 15;27(33):8940-51.
  • E.A. Stauffer, J. Scarborough, M. Hirono, E.D. Miller, K. Shah, J.A. Mercer, J. R. Holt, and P. G. Gillespie. (2005) Fast Adaptation in Vestibular Hair Cells Requires Myosin-1c Activity. Neuron. 47:541-553.
  • G.S.G. Géléoc and J.R. Holt. (2003) Developmental acquisition of sensory transduction in hair cells of the mouse inner ear. Nature Neuroscience 6(10), 1019-20.
  • J. R. Holt, S. K. H. Gillespie, D. W. Provance, Jr., K.Shah, K. M. Shokat, D. P. Corey, J. A. Mercer, and P. G. Gillespie. (2002) A chemical-genetic strategy implicates myosin 1c in adaptation by hair cells. Cell 108, 371-381, 2002.
  • PubMed Listings for this Faculty Member
    • Intranet Profile
    [To add/update Intranet profile information, read these instructions.]
    Contact Information
      Office Address: PO Box 801392, Lane Rd., MR-4, 5126, 
      Office Phone: +1 434-243-9995, +1 434-243-9499
      Fax Phone: +1 434-982-4380
      Mobile Phone: +1 434-996-7167

    Other Websites for this mentor:
    http://www.healthsystem.virginia.edu/internet/neurosci/Research/HoltLab/holtlab.cfm

    (Find Out How to Update Your Faculty Profile)