A. James Hudspeth is the F.M. Kirby Professor atRockefeller University in New York City, where he is director of the F.M. Kirby Center for Sensory Neuroscience. His laboratory studies the physiological basis ofhearing.
As a teenager, James Hudspeth spent his summers working as a technician in the lab of neurophysiologistPeter Kellaway atBaylor College of Medicine.[1] Hudspeth was expelled from high school for mixing dangerous chemicals and other mischief.[1]
Hudspeth graduated fromHarvard College in 1967, and received his master's degree fromHarvard University in 1968. He enrolled in a graduate program in neurobiology to avoid being drafted into the military, but a year later the policy was changed, requiring him to enter medical school for exemption. He studied under Nobel prize winnersTorsten Wiesel andDavid Hubel. He completed both programs and received his PhD in 1973 and MD in 1974, both fromHarvard University.[1][2]
Hudspeth's research is focused onsensorineural hearing loss, and the deterioration of thehair cells, the sensory cells of the cochlea.[5] Hudspeth's bold interpretation of the data obtained in his careful experimental research combined with biophysical modelling lead him to propose for the first time that the sense of hearing depends on a channel that is opened by mechanical force:[6] The hair cells located in theinner ear perceivesound when their apical end -consisting of a bundle of filaments- bends in response to the movement caused by this sound. The activated hair cell rapidly fills with calcium entering from the outside of the cell, which in turn activates the release of neurotransmitters that start a signal to the brain. Hudspeth proposed the existence of a "gating spring" opened by direct mechanical force that would open a hypothetical channel responsible for the entry of calcium ions. The hypothesis was based on the following evidence:[7] 1) Part of the energy needed to bend the filament bundle was mysteriously lost, but could be explained if it was used to opening this gating spring, 2) The entry of calcium ions was microseconds long, this is so fast that only direct opening -without a cascade of chemical reactions- could account for it and 3) Hudspeth tested a model analogue to the opening of a door with a string attached to the door knob and demonstrated that a similar process was taking place when the filaments of the hair cell moved. Furthermore, microscopic evidence showed the existence of such a string-like structure tethering the tip of one filament to the side of and adjacent filament that could be the elusive gating spring;[7] this string—called the tip link—would tense if the filament bundle was bent and then open the channel. Although the precise identity of the proteins forming the tip link[8] and the mechanosensitive channel[9] is still controversial 30 years later. Hudspeth's hypothesis was correct and fundamental for the understanding of the sense ofhearing.
Holton T & A.J. HudspethAMicromechanical contribution to cochlear tuning and tonotopic organization. Science (1983); 222 (4623): 508–510[10]
D.P. Corey, A.J. HudspethKinetics of the receptor current in bullfrog saccular hair cells. J. Neurosci., 3 (1983): 962-976[6]
Rosenblatt KP, Sun ZP, Heller S, A.J. Hudspeth Distribution of Ca2+-activated K+ channel isoforms along the tonotopic gradient of the chicken's cochlea. Neuron (1997): 19(5): 1061–1075[11] (note: this research was continued several years later taking advantage of newly available technology[12])
Lopez-Schier H, Starr CJ, Kappler JA, Kollmar R, A.J. Hudspeth Directional cell migration establishes the axes of planar polarity in the posterior lateral-line organ of the zebrafish. Dev CELL (2004): 7(3):401–412[14]
Chan DK, A.J. Hudspeth Ca2+ current-driven nonlinear amplification by the mammalian cochlea in vitro. Nature Neuro (2005): 8(2):149–155[15]
Kozlov AS, Risler T, A.J. Hudspeth Coherent motion of stereocilia assures the concerted gating of hair-cell transduction channels. Nature Neuro (2007): 10(1):87–92[16]
Kozlov AS, Baumgart J, Risler T, Versteegh CP, A.J. HudspethForces between clustered stereocilia minimize friction in the ear on a subnanometre scale. Nature. (2011): 474 (7351):376–9[17]
Fisher JA, Nin F, Reichenbach T, Uthaiah RC, A.J. Hudspeth The spatial pattern of cochlear amplification Neuron (2012): 76(5):989–9[18]
2002 Award of Merit, Association for Research in OtolaryngologyForces between clustered stereocilia minimize friction in the ear on a subnanometre scale.Kozlov AS, Baumgart J, Risler T, Versteegh CP, A.J. Hudspeth. Nature. 2011 May 22;474(7351):376-9. doi: 10.1038/nature10073.
^Holton, T.; Hudspeth, A. J. (1983). "In this study from 1983, quantitative measurements were made of the motion of individual hair bundles in an excised preparation of the cochlea stimulated at auditory frequencies. The angular displacement of hair bundles is frequency selective and tonotopically organized, demonstrating the existence of a micromechanical tuning mechanism".Science.222 (4623):508–10.doi:10.1126/science.6623089.PMID6623089.
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