Laboratory of Molecular Mechanisms of Auditory Perception and Deafness
The laboratory of Bo Zhao, PhD studies sensorineural hearing loss—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, part of the Department of Otolaryngology—Head and Neck Surgery at Indiana University School of Medicine, 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.
Zhao, associate professor of otolaryngology—head and neck surgery and a primary member of Stark Neurosciences Research Institute, has collected cochlear cell tissue to construct libraries for a yeast two-hybrid screening and examine interactions between proteins. In previous studies, Zhao has successfully used these libraries to illustrate the functions of two 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.
Active Grants
NIH R01, Taperin-based macromolecular complex at the base of stereocilia, 07/01/2018 – 02/28/2029
Li J, Liu C, Muller U, Zhao B (2023) Autophagy proteins are essential for aminoglycoside-induced hearing loss. Autophagy:1-2. PubMed
Li J, Liu C, Muller U, Zhao B (2022) RIPOR2-mediated autophagy dysfunction is critical for aminoglycoside-induced hearing loss. Dev Cell 57:2204-2220 e2206. PubMed
Liu C, Luo N, Zhao B (2022) Reducing Taperin Expression Restores Hearing in Grxcr2 Mutant Mice. Neuroscience 498:85-92. PubMed
Krey JF, Liu C, Belyantseva IA, Bateschell M, Dumont RA, Goldsmith J, Chatterjee P, Morrill RS, Fedorov LM, Foster S, Kim J, Nuttall AL, Jones SM, Choi D, Friedman TB, Ricci AJ, Zhao B, Barr-Gillespie PG (2022) ANKRD24 organizes TRIOBP to reinforce stereocilia insertion points. J Cell Biol 221. PubMed
Li J, Liu C, Zhao B (2022) Collapsin Response Mediator Protein 1 (CRMP1) Is Required for High-Frequency Hearing. Am J Pathol 192:805-812. PubMed
Li J, Liu C, Kaefer S, Youssef M, Zhao B (2022) The Mechanotransduction Channel and Organic Cation Transporter Are Critical for Cisplatin Ototoxicity in Murine Hair Cells. Front Mol Neurosci 15:835448. PubMed
Liu C, Zhao B (2021) Murine GRXCR1 Has a Different Function Than GRXCR2 in the Morphogenesis of Stereocilia. Front Cell Neurosci 15:714070. PubMed
McGrath J, Tung CY, Liao X, Belyantseva IA, Roy P, Chakraborty O, Li J, Berbari NF, Faaborg-Andersen CC, Barzik M, Bird JE, Zhao B, Balakrishnan L, Friedman TB, Perrin BJ (2021) Actin at stereocilia tips is regulated by mechanotransduction and ADF/cofilin. Curr Biol 31:1141-1153 e1147. PubMed
Li J, Liu C, Zhao B (2021) N-Terminus of GRXCR2 Interacts With CLIC5 and Is Essential for Auditory Perception. Front Cell Dev Biol 9:671364. PubMed
de Bruijn SE, Smits JJ, Liu C, Lanting CP, Beynon AJ, Blankevoort J, Oostrik J, Koole W, de Vrieze E, Cremers C, Cremers FPM, Roosing S, Yntema HG, Kunst HPM, Zhao B, Pennings RJE, Kremer H, Consortium D (2020) A RIPOR2 in-frame deletion is a frequent and highly penetrant cause of adult-onset hearing loss. J Med Genet. PubMed
Cunningham CL, Qiu X, Wu Z, Zhao B, Peng G, Kim YH, Lauer A, Muller U (2020) TMIE Defines Pore and Gating Properties of the Mechanotransduction Channel of Mammalian Cochlear Hair Cells. Neuron 107:126-143 e128. PubMed
Liu C, Luo N, Tung CY, Perrin BJ, Zhao B (2018) GRXCR2 Regulates Taperin Localization Critical for Stereocilia Morphology and Hearing. Cell Rep 25:1268-1280 e1264. PubMed
Dionne G, Qiu X, Rapp M, Liang X, Zhao B, Peng G, Katsamba PS, Ahlsen G, Rubinstein R, Potter CS, Carragher B, Honig B, Muller U, Shapiro L (2018) Mechanotransduction by PCDH15 Relies on a Novel cis-Dimeric Architecture. Neuron 99:480-492 e485. PubMed
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
Research Team
Bo Zhao, PhD
Associate Professor of Otolaryngology-Head & Neck Surgery
