DEPARTMENT OF NEUROBIOLOGY

Research Summary

Biophysics and Neurobiology of the Cochlea

Our work is focused on understanding the molecular and cellular bases of mammalian hearing. We focus on the functioning and role in the hearing process of the mammalian innovation: outer hair cells. These sensory receptors have motor capabilities and perform as the cochlear amplifier. Our latest work pertains to the study of the motor protein of outer hair cells. In 2000 we cloned the gene Prestin that codes for this molecular motor. When expressed in a heterologous cell system, prestin confers electromotility and nonlinear charge movement. We now study the properties of prestin and the electrophysiology of prestin knockout and knockin mice.

Selected Publications

• Cheatham, M.A., Goodyear, R., Homma, K., Legan, K., Korchagina, J., Naskar, S., Siegel, J. Dallos, P., Zheng, J., and Richardson, G. (2014). Loss of the Tectorial Membrane Protein, CEACAM16, Enhances Spontaneous, Stimulus-frequency and Transiently-evoked Otoacoustic Emissions. J. Neurosci, In press.
• Keller, J.P., Homma, K., Duan, C., Zheng, J. Cheatham, M.A. and Dallos, P. (2014). Functional regulation of the SLC26-family protein, prestin, by calcium/calmodulin. J. Neurosci, 34(4) 1325-1332.
• Zheng, J., Furness, D., Duan, C., Miller, K.K., Edge, R.M., Chen, J., Homma, K., Hackney, C.M., Dallos, P., and Cheatham, M.A. (2013). Marshalin, a microtubule minus-end binding protein, regulates cytoskeletal structure in the organ of Corti. Biology Open, 2(11) 1192-1202.
• Keller, J.P., Homma, K. and Dallos, P. (2013). Pixels as ROIs (PAR): a less-biased and statistically powerful approach for gleaning functional information from image stacks. Plos One, 8(7) e69047.
• Homma, K., Duan, C., Zheng, J. Cheatham, M.A. and Dallos, P. (2013). The V499G/Y501H mutation impairs prestin's fast motor kinetics and has significance for defining functional independence of individual prestin subunits. J. Biol. Chem, 288, 2452-2463.
• Homma, K. and Dallos, P. (2011). Dissecting the electromechanical coupling mechanism of the motor-protein prestin. Commmun. & Integrative Biol, 4, 450-453.
• Zheng, J., Miller, K.K., Yang, T., Hildebrand, M.S., Shearer, E.A., DeLuca, A.P., Sheetz, T.E., Drummond, J., Scherer, S., Legan, P.K., Goodyear, R., Richardson, R., Cheatham, M.A., Smith, R.J.H. and Dallos, P. (2011). Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with ?-tectorin and is mutated in autosomal dominant hearing loss (DFNA4). Proc. Natl. Acad. Sci. USA, 108, 4218-4223.
• Ashmore J, Avan P, Brownell WE, Dallos P, Dierkes K, Fettiplace R, Grosh K, Hackney CM, Hudspeth AJ, Jülicher F, Lindner B, Martin P, Meaud J, Petit C, Sacchi JR, Canlon B. (2010). The remarkable cochlear amplifier. Hear Res, Jul;266(1-2):1-17.
• Sengupta S, Miller KK, Homma K, Edge R, Cheatham MA, Dallos P, Zheng J. (2010). Interaction between the motor protein prestin and the transporter protein VAPA. Biochim Biophys Acta, Jul;1803(7):796-804
• Homma K, Miller KK, Anderson CT, Sengupta S, Du GG, Aguiñaga S, Cheatham M, Dallos P, Zheng J. (2010). Interaction between CFTR and prestin (SLC26A5). Biochim Biophys Acta, 2010 Jun;1798(6):1029-40.
• Cheatham MA, Low-Zeddies S, Naik K, Edge R, Zheng J, Anderson CT, Dallos P. (2009). A chimera analysis of prestin knock-out mice. J Neurosci, Sep 23;29(38):12000-8.
• Sengupta S, George M, Miller KK, Naik K, Chou J, Cheatham MA, Dallos P, Naramura M, Band H, Zheng J. (2009). EHD4 and CDH23 are interacting partners in cochlear hair cells. J Biol Chem, 24;284(30):20121-9.
• Zheng J, Anderson CT, Miller KK, Cheatham M, Dallos P. (2009). Identifying components of the hair-cell interactome involved in cochlear amplification. BMC Genomics, Mar 25;10:127.
• Dallos P. (2008). Cochlear amplification, outer hair cells and prestin. Curr Opin Neurobiol, 18(4):370-6.
• Dallos P, Wu X, Cheatham MA, Gao J, Zheng J, Anderson CT, Jia S, Wang X, Cheng WH, Sengupta S, He DZ, Zuo J. (2008). Prestin-based outer hair cell motility is necessary for mammalian cochlear amplification. Neuron, 58(3):333-9.
• Wu X, Wang X, Gao J, Yu Y, Jia S, Zheng J, Dallos P, He DZ, Cheatham M, Zuo J. (2008). Glucose transporter 5 is undetectable in outer hair cells and does not contribute to cochlear amplification. Brain Research, 210:20-8.
• Cheatham MA, Zheng J, Huynh KH, Du GG, Edge RM, Anderson CT, Zuo J, Ryan AF, Dallos P. (2007). Evaluation of an independent prestin mouse model derived from the 129S1 strain. Audiol Neurootol, 12(6):378-90.
• Gao J, Wang X, Wu X, Aguinaga S, Huynh K, Jia S, Matsuda K, Patel M, Zheng J, Cheatham M, He DZ, Dallos P, Zuo J. (2007). Prestin-based outer hair cell electromotility in knockin mice does not appear to adjust the operating point of a cilia-based amplifier. Proc Natl Acad Sci U S A, Jul 24;104(30):12542-7
• Richter CP, Emadi G, Getnick G, Quesnel A, Dallos P. Tectorial membrane stiffness gradients. (2007). Biophysical Journal, 93(6):2265-76.
• PubMed

Selected Honors/Awards

• 2008  Life Achievement Award, American Auditory Society
• 2005  Hugh Knowles Prize
• 2004  Guyot Prize, University of Groningen, The Netherlands
• 2004  Honorary Member, Hungarian Academy of Sciences
• 2000  Kresge-Mirmelstein Award
• 1997-00  Senior Investigator Award, The McKnight Endowment Fund for Neuroscience
• 1997  Fellow of the American Academy of Arts and Sciences
• 1997  Acta Otolaryngologica International Prize
• 1997-98  Sigma Xi Distinguished National Lecturer
• 1995  von Békésy Medal of the Acoustical Society of America
• 1994  Honors of the Association, American Speech, Language and Hearing Association
• 1994  Award of Merit, Association for Research in Otolaryngology
• 1977-78  Recipient of John Simon Guggenheim Fellowship for research in auditory physiology