A. James Hudspeth

A. James Hudspeth is the F.M. Kirby Professor at Rockefeller University, where he is director of the F.M. Kirby Center for Sensory Neuroscience. His laboratory studies the physiological basis of hearing.

A. James Hudspeth
Alma mater
AwardsKavli Prize in Neuroscience (2018)
Scientific career
Institutions

Early life and education

As a teenager, James Hudspeth spent his summers working as a technician in the lab of neurophysiologist Peter Kellaway at Baylor College of Medicine.[1] Hudspeth was expelled from high school for mixing dangerous chemicals and other mischief.[1]

Hudspeth graduated from Harvard College in 1967, and received his master's degree from Harvard 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 winners Torsten Wiesel and David Hubel. He completed both programs and received his PhD in 1973 and MD in 1974, both from Harvard University.[1][2]

He began a postdoctoral fellowship with Åke Flock at the Karolinska Institute, but left early without much success to return to Harvard Medical School.[1][2]

Career

Following his postdoctoral training, Hudspeth was a professor at CalTech from 1975 to 1983.[2] He then moved to the UCSF School of Medicine where he was a professor from 1983 to 1989. He directed the neuroscience program at University of Texas Southwestern Medical Center from 1989 until 1995, when the department was closed.[1] In 1995, he was recruited to the Rockefeller University.[1][3]

Hudspeth has been an HHMI investigator since 1993.[4]

Research

Hudspeth's research is focused on sensorineural hearing loss, and the deterioration of the hair 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 the inner ear perceive sound 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 an 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 bend 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 of hearing.

Noted publications
  • Holton T & A.J. Hudspeth A Micromechanical contribution to cochlear tuning and tonotopic organization. Science (1983); 222 (4623): 508-510[10]
  • D.P. Corey, A.J. Hudspeth Kinetics 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])
  • A.J. Hudspeth How hearing happens. NEURON (1997): 19(5): 947-950[13]
  • 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. Hudspeth Forces 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]

Awards

References
  1. "The Ears Have It". The Scientist.
  2. "A. James Hudspeth - Our Scientists". Our Scientists.
  3. "The Rockefeller University » Scientists & Research". www2.rockefeller.edu.
  4. "A. James Hudspeth, MD, PhD | HHMI.org". HHMI.org.
  5. "James Hudspeth, MD, PhD | Duke Neurobiology". www.neuro.duke.edu. Archived from the original on 2016-03-09. Retrieved 2018-05-23.
  6. Hudspeth, A. J.; Corey, D. P. (May 1983). "Corey, D.P., Hudspeth, A.J. (1983) Kinetics of the receptor current in bullfrog saccular hair cells J Neuro 3 (5): 962-976 : In this paper, the direct mechanical opening necessary for the sense of hearing is stated for the first time". Journal of Neuroscience. 3 (5): 962–976. doi:10.1523/JNEUROSCI.03-05-00962.1983.
  7. Hudspeth, A. J. (1989). "AJ Hudspeth (1989) How the ear's works work Nature 341 page 397-404". Nature. 341 (6241): 397–404. doi:10.1038/341397a0. PMID 2677742. S2CID 33117543.
  8. Bartsch, T. F.; Hengel, F. E.; Oswald, A.; Dionne, G.; Chipendo, I. V.; Mangat, S. S.; El Shatanofy, M.; Shapiro, L.; Müller, U.; Hudspeth, A. J. (2019). "Bartsch TF & Hudspeth AJ. et al (2019) Elasticity of individual protocadherin 15 molecules implicates tip links as the gating springs for hearing. Proc Natl Acad Sci U S A. 28; 116(22):11048-11056". Proceedings of the National Academy of Sciences of the United States of America. 116 (22): 11048–11056. doi:10.1073/pnas.1902163116. PMC 6561218. PMID 31072932.
  9. Qiu, X.; Müller, U. (2018). "Qiu, X., & Müller, U. (2018). Mechanically Gated Ion Channels in Mammalian Hair Cells. Frontiers in cellular neuroscience, 12, 100". Frontiers in Cellular Neuroscience. 12: 100. doi:10.3389/fncel.2018.00100. PMC 5932396. PMID 29755320.
  10. 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. PMID 6623089.
  11. Rosenblatt, K. P.; Sun, Z. P.; Heller, S.; Hudspeth, A. J. (1997). "This landmark research has been featured in the textbook "Molecular Cell Biology" by JE Darnell". Neuron. 19 (5): 1061–75. doi:10.1016/S0896-6273(00)80397-9. PMID 9390519. S2CID 18165145.
  12. Miranda-Rottmann, S.; Kozlov, A. S.; Hudspeth, A. J. (2010). "Revisiting how a molecular gradient of a potassium channel allows the chicken cochlea to sense progressively lower tones along its structure". Molecular and Cellular Biology. 30 (14): 3646–60. doi:10.1128/MCB.00073-10. PMC 2897565. PMID 20479127.
  13. Hudspeth, A. J. (November 1997). "In this review AJ Hudspeth explains the biophysics of the hearing in the light of his own vast contribution to the field". Neuron. 19 (5): 947–950. doi:10.1016/S0896-6273(00)80385-2. PMID 9390507. S2CID 16020028.
  14. López-Schier, H.; Starr, C. J.; Kappler, J. A.; Kollmar, R.; Hudspeth, A. J. (2004). "This research shows the embryonic development of the har cells necessary for the zebrafish directional movement in the water". Developmental Cell. 7 (3): 401–12. doi:10.1016/j.devcel.2004.07.018. PMID 15363414.
  15. Chan, D. K.; Hudspeth, A. J. (2005). "These results suggest that the Ca2+ current drives the cochlear active process, and they support the hypothesis that active hair-bundle motility underlies cochlear amplification". Nature Neuroscience. 8 (2): 149–55. doi:10.1038/nn1385. PMC 2151387. PMID 15643426.
  16. Kozlov, A. S.; Risler, T.; Hudspeth, A. J. (2007). "Research showing the coordinated movement of the entire hair cell filament bundle". Nature Neuroscience. 10 (1): 87–92. doi:10.1038/nn1818. PMC 2174432. PMID 17173047.
  17. Hudspeth, A. J.; Versteegh, Corstiaen P. C.; Risler, Thomas; Baumgart, Johannes; Kozlov, Andrei S. (June 2011). "A combination of high-resolution experiments and detailed numerical modelling of fluid-structure interactions reveals the physical principles behind the basic structural features of hair bundles and shows quantitatively how these organelles are adapted to the needs of sensitive mechanotransduction". Nature. 474 (7351): 376–379. doi:10.1038/nature10073. PMC 3150833. PMID 21602823.
  18. Fisher, J. A.; Nin, F.; Reichenbach, T.; Uthaiah, R. C.; Hudspeth, A. J. (2012). "The spatial pattern of cochlear amplification note: featured as a cover of this journal issue". Neuron. 76 (5): 989–97. doi:10.1016/j.neuron.2012.09.031. PMC 3721062. PMID 23217746.
  19. Louisa Gross Horwitz Prize 2020
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