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Heads of Laboratories

Head shot of A. Hudspeth
A. James Hudspeth, M.D., Ph.D.
Investigator, Howard Hughes Medical Institute
F.M. Kirby Professor
Laboratory of Sensory Neuroscience
A.James.Hudspeth@rockefeller.edu

The majority of the hearing impaired suffer from sensorineural hearing loss, which usually results from damage to the hair cells of the inner ear. The human cochlea contains about 16,000 of these hair cells, which do not regenerate after damage. As an initial step toward the prevention or reversal of deafness, Dr. Hudspeth’s laboratory is working to better understand the normal hearing process and causes of hearing deterioration.

Within the cochlea, mechanical signals representing sound are converted into vibrations along the basilar membrane upon which some 16,000 hair cells stand. 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 Dr. Hudspeth’s lab 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 a distance of ±30 nm. When a small stimulus force is applied to an active bundle, the bundle’s 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 low-frequency sounds are amplified. 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, Dr. Hudspeth’s group is conducting molecular-biological experiments on the larval zebrafish. In the lateral line of this species, new hair cells arise continually 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, the other sensitive to posterior flow. In the hope of establishing what signaling pathways lead to the production of new hair cells, members of the group are isolating both 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. Other experimenters are studying how individual nerve fibers distinguish between hair cells of the two functional polarities, selectively innervating only one of the two sets.

Dr. 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.



EDUCATION

B.A. in biochemical sciences, 1967
Harvard College

M.A. in neurobiology, 1968
Ph.D. in neurobiology, 1973
Harvard University

M.D., 1974
Harvard Medical School

POSTDOC

Karolinska Institute, 1974

Harvard Medical School, 1975

POSITIONS

Assistant Professor, 1975–1978
Associate Professor, 1978–1982
Professor, 1982–1983
California Institute of Technology

Professor, 1983–1989
University of California, San Francisco, School of Medicine

Professor, 1989–1995
University of Texas Southwestern Medical Center

Professor, 1995–
Director, F.M. Kirby Center for Sensory Neuroscience, 1997–
The Rockefeller University

Investigator, 1993–
Howard Hughes Medical Institute

AWARDS

W. Alden Spencer Award, 1985

K.S. Cole Award, Biophysical Society, 1991

Charles A. Dana Award, 1994

Award of Merit, Association for Research in Otolaryngology, 2002

Ralph W. Gerard Prize, Society for Neuroscience, 2003

Guyot Prize, University of Groningen, 2010

MEMBERSHIPS

National Academy of Sciences
American Academy of Arts and Sciences
American Philosophical Society

SELECTED PUBLICATIONS

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).

Steiner, A.B. et al. Dynamic gene expression by putative hair-cell progenitors during regeneration in the zebrafish lateral line. Proc. Natl. Acad. Sci. U.S.A. 111, E1393–E1401 (2014).

Fisher, J.A. et al. The spatial pattern of cochlear amplification. Neuron 76, 989–997 (2012).


Dr. Hudspeth is a faculty member in the David Rockefeller Graduate Program and the Tri-Institutional M.D.-Ph.D. Program.