Laboratory of Molecular Mechanisms of Auditory Perception and Deafness
PI: Bo Zhao, PhD
Sensorineural hearing loss is the most common type of hearing loss. It is most often caused by defects in cochlear hair cells, the primary sensors for sound that convert mechanical sound stimuli into electrical signals that are transmitted to the nervous system. Approximately 135 genetic loci have been linked to hearing loss, and about 60 affected genes have been identified. However, the physiological functions of these genes are not well-studied. The Laboratory of Molecular Mechanisms of Auditory Perception and Deafness is finding the ability to illustrate the functions of these genes – and discover new ones – that could provide fresh leads for developing novel treatments for some forms of hearing loss.
Bo Zhao, PhD, recently collected cochlear cell tissue to construct libraries for yeast two-hybrid screening and examine interactions between proteins. In previous studies, Zhao has successfully used these libraries to illustrate the functions of two deafness proteins linked to hearing loss. Continued work aims to reveal the functions of other deafness-related genes and uncover other genes linked to hearing loss. The Laboratory of Molecular Mechanisms of Auditory Perception and Deafness is a part of the Department of Otolaryngology – Head and Neck Surgery.
NIH R01, Functions of Fam65b protein complex at the basal stereocilia in hearing and deafness, 07/01/2018 – 06/30/2023
Showalter Young Investigator Award, 07/01/2018 – 06/30/2019
Cunningham CL, Wu Z, Jafari A, Zhao B, Schrode K, Harkins-Perry S, Lauer A, Müller U. “The murine catecholamine methyltransferase mTOMT is essential for mechanotransduction by cochlear hair cells.” eLife. 2017 May 15;6. PMID: 28504928
Wu Z*, Grillet N*, Zhao B, Cunningham C, Harkins-Perry S, Coste B, Ranade S, Zebarjadi N, Beurg M, Fettiplace R, Patapoutian A, Müller U. “Mechanosensory hair cells express two molecularly distinct mechanotransduction channels.” Nat Neurosci. 2017 Jan;20(1):24-33. PMID: 27893727
Morgan CP*, Krey JF*, Grati M, Zhao B, Fallen S, Kannan-Sundhari A, Liu XZ, Choi D, Müller U, and Barr-Gillespie PG. “PDZD7-MYO7A complex identified in enriched stereocilia membranes.” eLife. 2016 Aug 15;5. PMID 27525485
Zhao B*, Wu Z, Müller U. “Murine Fam65b forms ring-like structures at the base of stereocilia critical for mechanosensory hair cell function.” eLife. 2016 June 8;5. PMID: 27269051
Zhao B*, Müller U. “The Elusive Mechanotransduction Machinery of Hair Cells: Molecules and Models.” Curr Opin Neurobiol. 2015 Oct;34:172-9. PMID: 26342686
Beurg M*, Xiong W, Zhao B, Müller U, Fettiplace R. “Subunit determination of the conductance of hair-cell mechanotransducer channels.” Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1589-94. PMID: 25550511
Zhao B*, Wu Z, Grillet N, Yan L, Xiong W, Harkins-Perry S, Müller U. “TMIE is an essential component of the mechanotransduction machinery of cochlear hair cells.” Neuron. 2014 Dec 3;84(5):954-67. PMID: 25467981
Xiong W*, Grillet N, Elledge HM, Wagner TF, Zhao B, Johnson KR, Kazmierczak P, Müller U. “TMHS is an Integral Component of the Mechanotransduction Machinery of Cochlear Hair Cells.” Cell. 2012 Dec 7;151(6):1283-95. PMID: 23217710
He SQ*, Zhang ZN*, Guan JS*, Liu HR, Zhao B, Wang HB, Li Q, Yang H, Luo J, Li ZY, Wang Q, Bao L, Zhang X. “Facilitation of μ-opioid receptor activity by preventing δ-opioid receptor-mediated codegradation.” Neuron. 2011 Jan 13;69(1):120-31. PMID: 21220103
Zhao B*, Wang HB*, Lu YJ, Hu JW, Bao L, Zhang X. “Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles.” Cell Res. 2011 May;21(5):741-53. PMID: 21321602
Wang HB*, Zhao B*, Zhong YQ*, Li KC, Li ZY, Wang Q, Lu YJ, Zhang ZN, He SQ, Zheng HC, Wu SX, Hökfelt TG, Bao L, Zhang X. “Co-expression of delta- and mu-opioid receptors in nociceptive sensory neurons.” Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13117-22. PMID: 20615975
Additional Lab Members
Additional lab members include Chang Liu, PhD (postdoctoral fellow), Na Luo, PhD (research associate) and Linette Staley (grant coordinator).