Heads of Laboratories
Investigator, Howard Hughes Medical Institute
F.M. Kirby Professor
Laboratory of Sensory Neuroscience
The majority of the hearing-impaired suffer from sensorineural hearing loss resulting from damage to the sensory hair cells of the inner ear. The human cochlea contains about 16,000 of these cells, which do not regenerate after damage. In an effort to prevent or reverse deafness, Hudspeth’s group is working to better understand the normal hearing process, the causes of hearing deterioration, and possible means to regenerate hair cells.
Within the cochlea, mechanical signals representing sound are converted into vibrations along the basilar membrane, upon which stand some 16,000 hair cells. Each hair cell is endowed with a few hundred fine “feelers,” or stereocilia, that collectively constitute its hair bundle. Sound-induced vibrations set the hair bundle in motion, evoking electrical responses by opening and closing mechanically sensitive ion channels. As a result of the direct mechanical connection between the hair bundle and ion channels, the transduction process of hair cells is remarkably rapid; we can consequently hear sounds at frequencies as great as 20 kHz. The direct nature of auditory transduction also makes the process highly sensitive.
The extraordinary sensitivity of our hearing suggests that the cochlea amplifies its mechanical inputs, and researchers in Hudspeth’s research group are exploring how human hearing benefits from a tiny mechanical amplifier in each hair bundle. They have found that bundles are spontaneously active, oscillating through an approximate distance of 30 nm. When an active bundle is subjected to a small stimulus force, its motion becomes synchronized with the stimulus. Measurement of the mechanical work performed in this situation confirms that a hair bundle can amplify and tune its mechanical inputs. Members of the research group are now extending these results to the mammalian ear. Using a theoretical approach to model the cochlea, they are also exploring the mechanism by which it amplifies sounds. Identifying the active process in the human cochlea is especially important because hearing loss usually begins with deterioration of this amplifier.
In an effort to learn how hair cells develop, Hudspeth’s group is conducting molecular-biological experiments on the larval zebrafish. In the lateral line of this species, new hair cells continually arise to replace those that die as a result of aging or chemical toxicity. The division of a precursor cell consistently produces a pair of hair cells, one of which responds to water movement toward the animal’s anterior while the other is sensitive to posterior flow. To establish which signaling pathways lead to the production of new hair cells, members of the group are isolating hair cells and their precursors, and examining their gene expression. The investigators hope to identify pathways that might be activated in the human ear to foster the replacement of hair cells.
The team is also studying how individual nerve fibers distinguish between hair cells of the two functional polarities, selectively innervating only one of the two sets. Finally, some members of the lab are investigating the regeneration of hair cells in the inner ear of the mouse, a preparation that resembles the human inner ear.
Hudspeth’s research has led to a deepened understanding of the receptor cells of the inner ear and how they contribute to hearing and hearing loss. He hopes that further investigation will indicate both the causes of and potential remedies for certain forms of human hearing impairment, an affliction that affects 10 percent of the American population.
B.A. in biochemical sciences, 1967
M.A. in neurobiology, 1968
Ph.D. in neurobiology, 1973
Harvard Medical School
Karolinska Institute, 1974
Harvard Medical School, 1975
Assistant Professor, 1975–1978
Associate Professor, 1978–1982
California Institute of Technology
University of California, San Francisco, School of Medicine
University of Texas Southwestern Medical Center
Director, F.M. Kirby Center for Sensory Neuroscience, 1997–
The Rockefeller University
Howard Hughes Medical Institute
W. Alden Spencer Award, 1985
K.S. Cole Award, Biophysical Society, 1991
Charles A. Dana Award, 1994
Lewis S. Rosenstiel Award, 1997
Award of Merit, Association for Research in Otolaryngology, 2002
Ralph W. Gerard Prize, Society for Neuroscience, 2003
The Rockefeller University Distinguished Teaching Award, 2009
Guyot Prize, University of Groningen, 2010
Kavli Prize in Neuroscience, 2018
National Academy of Sciences
American Academy of Arts and Sciences
American Philosophical Society
Basu, A. et al. Direct mechanical stimulation of tip links in hair cells through DNA tethers. Elife 5, e16041 (2016).
Gnedeva, K. and Hudspeth, A.J. SoxC transcription factors are essential for the development of the inner ear. Proc. Natl. Acad. Sci. U.S.A. 112, 14066–14071 (2015).
Dow, E. et al. Cellular projections from sensory hair cells form polarity-specific scaffolds during synaptogenesis. Genes Dev. 29, 1087–1094 (2015).
Salvi, J.D. et al. Control of a hair bundle’s mechanosensory function by its mechanical load. Proc. Natl. Acad. Sci. U.S.A. 112, E1000–E1009 (2015).
Jacobo, A. and Hudspeth, A.J. Reaction-diffusion model of hair-bundle morphogenesis. Proc. Natl. Acad. Sci. U.S.A. 111, 15444–15449 (2014).