Hong-Bo Zhao, MD, PhD
Professor of Surgery (Otolaryngology); Professor, Surgery - Otolaryngology
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Research Summary
Our auditory research lab currently mainly focuses on 1) deafness mechanisms underlying Cx26 (GJB2) gap junction gene mutations induced hearing loss, 2) mechanisms underlying noise-induced cochlear synaptopathy and hearing loss, and 3) functional and pathological changes of Alzheimer's disease in hearing system. Based on these studies, we are planning to develop gene therapy for Cx26 mutation induced deafness, which is responsible for >50% of nonsyndromic heretical hearing loss in clinic. We will also develop a post-noise treatment, and identify and provide early hearing biomarkers for early AD detection. Both of them have important significance in treatment of noise-induced hearing loss and the AD prevention and treatment.
Extensive Research Description
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Selected Publications
- Hearing loss promotes Alzheimer’s diseaseZhao H, Yang Y. Hearing loss promotes Alzheimer’s disease. Nature Aging 2024, 4: 443-444. PMID: 38491290, DOI: 10.1038/s43587-024-00606-2.
- Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noiseLiu L, Liang C, Chen J, Fang S, Zhao H. Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise. Science Advances 2023, 9: eadf4144. PMID: 36753545, PMCID: PMC9908021, DOI: 10.1126/sciadv.adf4144.
- Efferent neurons control hearing sensitivity and protect hearing from noise through the regulation of gap junctions between cochlear supporting cellsZhao H, Liu L, Yu N, Zhu Y, Mei L, Chen J, Liang C. Efferent neurons control hearing sensitivity and protect hearing from noise through the regulation of gap junctions between cochlear supporting cells. Journal Of Neurophysiology 2021, 127: 313-327. PMID: 34907797, PMCID: PMC8759971, DOI: 10.1152/jn.00468.2021.
- Early Functional and Cognitive Declines Measured by Auditory-Evoked Cortical Potentials in Mice With Alzheimer’s DiseaseMei L, Liu L, Chen K, Zhao H. Early Functional and Cognitive Declines Measured by Auditory-Evoked Cortical Potentials in Mice With Alzheimer’s Disease. Frontiers In Aging Neuroscience 2021, 13: 710317. PMID: 34588972, PMCID: PMC8473830, DOI: 10.3389/fnagi.2021.710317.
- Excess extracellular K+ causes inner hair cell ribbon synapse degenerationZhao H, Zhu Y, Liu L. Excess extracellular K+ causes inner hair cell ribbon synapse degeneration. Communications Biology 2021, 4: 24. PMID: 33398038, PMCID: PMC7782724, DOI: 10.1038/s42003-020-01532-w.
- Hearing loss is an early biomarker in APP/PS1 Alzheimer’s disease miceLiu Y, Fang S, Liu L, Zhu Y, Li C, Chen K, Zhao H. Hearing loss is an early biomarker in APP/PS1 Alzheimer’s disease mice. Neuroscience Letters 2019, 717: 134705. PMID: 31870800, PMCID: PMC7004828, DOI: 10.1016/j.neulet.2019.134705.
- Knockout of Pannexin-1 Induces Hearing LossChen J, Liang C, Zong L, Zhu Y, Zhao H. Knockout of Pannexin-1 Induces Hearing Loss. International Journal Of Molecular Sciences 2018, 19: 1332. PMID: 29710868, PMCID: PMC5983795, DOI: 10.3390/ijms19051332.
- P2X2 Dominant Deafness Mutations Have No Negative Effect on Wild-Type Isoform: Implications for Functional Rescue and in Deafness MechanismZhu Y, Beudez J, Yu N, Grutter T, Zhao H. P2X2 Dominant Deafness Mutations Have No Negative Effect on Wild-Type Isoform: Implications for Functional Rescue and in Deafness Mechanism. Frontiers In Molecular Neuroscience 2017, 10: 371. PMID: 29180951, PMCID: PMC5693881, DOI: 10.3389/fnmol.2017.00371.
- A deafness mechanism of digenic Cx26 (GJB2) and Cx30 (GJB6) mutations: Reduction of endocochlear potential by impairment of heterogeneous gap junctional function in the cochlear lateral wallMei L, Chen J, Zong L, Zhu Y, Liang C, Jones R, Zhao H. A deafness mechanism of digenic Cx26 (GJB2) and Cx30 (GJB6) mutations: Reduction of endocochlear potential by impairment of heterogeneous gap junctional function in the cochlear lateral wall. Neurobiology Of Disease 2017, 108: 195-203. PMID: 28823936, PMCID: PMC5675824, DOI: 10.1016/j.nbd.2017.08.002.
- Hypothesis of K+-Recycling Defect Is Not a Primary Deafness Mechanism for Cx26 (GJB2) DeficiencyZhao H. Hypothesis of K+-Recycling Defect Is Not a Primary Deafness Mechanism for Cx26 (GJB2) Deficiency. Frontiers In Molecular Neuroscience 2017, 10: 162. PMID: 28603488, PMCID: PMC5445178, DOI: 10.3389/fnmol.2017.00162.
- Progressive age-dependence and frequency difference in the effect of gap junctions on active cochlear amplification and hearingZong L, Chen J, Zhu Y, Zhao H. Progressive age-dependence and frequency difference in the effect of gap junctions on active cochlear amplification and hearing. Biochemical And Biophysical Research Communications 2017, 489: 223-227. PMID: 28552523, PMCID: PMC5555358, DOI: 10.1016/j.bbrc.2017.05.137.
- Expression and function of pannexins in the inner ear and hearingZhao H. Expression and function of pannexins in the inner ear and hearing. BMC Molecular And Cell Biology 2016, 17: 16. PMID: 27229462, PMCID: PMC4896268, DOI: 10.1186/s12860-016-0095-7.
- Gap junction mediated miRNA intercellular transfer and gene regulation: A novel mechanism for intercellular genetic communicationZong L, Zhu Y, Liang R, Zhao H. Gap junction mediated miRNA intercellular transfer and gene regulation: A novel mechanism for intercellular genetic communication. Scientific Reports 2016, 6: 19884. PMID: 26814383, PMCID: PMC4728487, DOI: 10.1038/srep19884.
- Connexin26 gap junction mediates miRNA intercellular genetic communication in the cochlea and is required for inner ear developmentZhu Y, Zong L, Mei L, Zhao H. Connexin26 gap junction mediates miRNA intercellular genetic communication in the cochlea and is required for inner ear development. Scientific Reports 2015, 5: 15647. PMID: 26490746, PMCID: PMC4614881, DOI: 10.1038/srep15647.
- Pannexin1 channels dominate ATP release in the cochlea ensuring endocochlear potential and auditory receptor potential generation and hearingChen J, Zhu Y, Liang C, Chen J, Zhao H. Pannexin1 channels dominate ATP release in the cochlea ensuring endocochlear potential and auditory receptor potential generation and hearing. Scientific Reports 2015, 5: 10762. PMID: 26035172, PMCID: PMC4451810, DOI: 10.1038/srep10762.
- Cellular and Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss – A Common Hereditary DeafnessWingard J, Zhao H. Cellular and Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss – A Common Hereditary Deafness. Frontiers In Cellular Neuroscience 2015, 9: 202. PMID: 26074771, PMCID: PMC4448512, DOI: 10.3389/fncel.2015.00202.
- Pannexin 1 deficiency can induce hearing lossZhao H, Zhu Y, Liang C, Chen J. Pannexin 1 deficiency can induce hearing loss. Biochemical And Biophysical Research Communications 2015, 463: 143-147. PMID: 26002464, PMCID: PMC4464954, DOI: 10.1016/j.bbrc.2015.05.049.
- Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing lossZhu Y, Chen J, Liang C, Zong L, Chen J, Jones R, Zhao H. Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss. Neuroscience 2014, 284: 719-729. PMID: 25451287, PMCID: PMC4268423, DOI: 10.1016/j.neuroscience.2014.10.061.
- Deafness induced by Connexin 26 (GJB2) deficiency is not determined by endocochlear potential (EP) reduction but is associated with cochlear developmental disordersChen J, Chen J, Zhu Y, Liang C, Zhao H. Deafness induced by Connexin 26 (GJB2) deficiency is not determined by endocochlear potential (EP) reduction but is associated with cochlear developmental disorders. Biochemical And Biophysical Research Communications 2014, 448: 28-32. PMID: 24732355, PMCID: PMC4105360, DOI: 10.1016/j.bbrc.2014.04.016.
- The role of an inwardly rectifying K+ channel (Kir4.1) in the inner ear and hearing lossChen J, Zhao H. The role of an inwardly rectifying K+ channel (Kir4.1) in the inner ear and hearing loss. Neuroscience 2014, 265: 137-146. PMID: 24480364, PMCID: PMC4007161, DOI: 10.1016/j.neuroscience.2014.01.036.
- The effects and outcomes of electrolyte disturbances and asphyxia on newborns hearingLiang C, Hong Q, Jiang T, Gao Y, Yao X, Luo X, Zhuo X, Shinn J, Jones R, Zhao H, Lu G. The effects and outcomes of electrolyte disturbances and asphyxia on newborns hearing. International Journal Of Pediatric Otorhinolaryngology 2013, 77: 1072-1076. PMID: 23648318, PMCID: PMC3738180, DOI: 10.1016/j.ijporl.2013.03.031.
- Active cochlear amplification is dependent on supporting cell gap junctionsZhu Y, Liang C, Chen J, Zong L, Chen G, Zhao H. Active cochlear amplification is dependent on supporting cell gap junctions. Nature Communications 2013, 4: 1786. PMID: 23653198, PMCID: PMC3675877, DOI: 10.1038/ncomms2806.
- Mutation of the ATP-gated P2X2 receptor leads to progressive hearing loss and increased susceptibility to noiseYan D, Zhu Y, Walsh T, Xie D, Yuan H, Sirmaci A, Fujikawa T, Wong A, Loh T, Du L, Grati M, Vlajkovic S, Blanton S, Ryan A, Chen Z, Thorne P, Kachar B, Tekin M, Zhao H, Housley G, King M, Liu X. Mutation of the ATP-gated P2X2 receptor leads to progressive hearing loss and increased susceptibility to noise. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 2228-2233. PMID: 23345450, PMCID: PMC3568371, DOI: 10.1073/pnas.1222285110.
- Cell degeneration is not a primary causer for Connexin26 (GJB2) deficiency associated hearing lossLiang C, Zhu Y, Zong L, Lu G, Zhao H. Cell degeneration is not a primary causer for Connexin26 (GJB2) deficiency associated hearing loss. Neuroscience Letters 2012, 528: 36-41. PMID: 22975134, PMCID: PMC3467974, DOI: 10.1016/j.neulet.2012.08.085.
- ATP activates P2X receptors to mediate gap junctional coupling in the cochleaZhu Y, Zhao H. ATP activates P2X receptors to mediate gap junctional coupling in the cochlea. Biochemical And Biophysical Research Communications 2012, 426: 528-532. PMID: 22982314, PMCID: PMC3471361, DOI: 10.1016/j.bbrc.2012.08.119.
- Pannexin channels are not gap junction hemichannelsSosinsky G, Boassa D, Dermietzel R, Duffy H, Laird D, MacVicar B, Naus C, Penuela S, Scemes E, Spray D, Thompson R, Zhao H, Dahl G. Pannexin channels are not gap junction hemichannels. Channels 2011, 5: 193-197. PMID: 21532340, PMCID: PMC3704572, DOI: 10.4161/chan.5.3.15765.
- ATP-mediated potassium recycling in the cochlear supporting cellsZhu Y, Zhao H. ATP-mediated potassium recycling in the cochlear supporting cells. Purinergic Signalling 2010, 6: 221-229. PMID: 20806014, PMCID: PMC2912999, DOI: 10.1007/s11302-010-9184-9.
- Identification and Characterization of Pannexin Expression in the Mammalian CochleaWang X, Streeter M, Liu Y, Zhao H. Identification and Characterization of Pannexin Expression in the Mammalian Cochlea. The Journal Of Comparative Neurology 2010, 518: 1156-1156. DOI: 10.1002/cne.22315.
- Modulation of Outer Hair Cell Electromotility by Cochlear Supporting Cells and Gap JunctionsYu N, Zhao H. Modulation of Outer Hair Cell Electromotility by Cochlear Supporting Cells and Gap Junctions. PLOS ONE 2009, 4: e7923. PMID: 19936276, PMCID: PMC2775161, DOI: 10.1371/journal.pone.0007923.
- Identification and characterization of pannexin expression in the mammalian cochleaWang X, Streeter M, Liu Y, Zhao H. Identification and characterization of pannexin expression in the mammalian cochlea. The Journal Of Comparative Neurology 2008, 512: 336-346. PMID: 19009624, PMCID: PMC2630187, DOI: 10.1002/cne.21898.
- Cellular characterization of Connexin26 and Connnexin30 expression in the cochlear lateral wallLiu Y, Zhao H. Cellular characterization of Connexin26 and Connnexin30 expression in the cochlear lateral wall. Cell And Tissue Research 2008, 333: 395. PMID: 18581144, PMCID: PMC2548271, DOI: 10.1007/s00441-008-0641-5.
- Prestin up-regulation in chronic salicylate (aspirin) administration: An implication of functional dependence of prestin expressionYu N, Zhu M, Johnson B, Liu Y, Jones R, Zhao H. Prestin up-regulation in chronic salicylate (aspirin) administration: An implication of functional dependence of prestin expression. Cellular And Molecular Life Sciences 2008, 65: 2407-2418. PMID: 18560754, PMCID: PMC2548279, DOI: 10.1007/s00018-008-8195-y.
- ATP activates P2x receptors and requires extracellular Ca++ participation to modify outer hair cell nonlinear capacitanceYu N, Zhao H. ATP activates P2x receptors and requires extracellular Ca++ participation to modify outer hair cell nonlinear capacitance. Pflügers Archiv - European Journal Of Physiology 2008, 457: 453-461. PMID: 18491132, PMCID: PMC5531446, DOI: 10.1007/s00424-008-0522-5.
- Hemichannel-Mediated Inositol 1,4,5-Trisphosphate (IP3) Release in the Cochlea: A Novel Mechanism of IP3 Intercellular SignalingGossman D, Zhao H. Hemichannel-Mediated Inositol 1,4,5-Trisphosphate (IP3) Release in the Cochlea: A Novel Mechanism of IP3 Intercellular Signaling. Cell Communication & Adhesion 2008, 15: 305-315. PMID: 18979296, PMCID: PMC5543712, DOI: 10.1080/15419060802357217.
- Distinct and gradient distributions of connexin26 and connexin30 in the cochlear sensory epithelium of guinea pigsZhao H, Yu N. Distinct and gradient distributions of connexin26 and connexin30 in the cochlear sensory epithelium of guinea pigs. The Journal Of Comparative Neurology 2006, 499: 506-518. PMID: 16998915, PMCID: PMC2553046, DOI: 10.1002/cne.21113.
- Effects of intense noise exposure on the outer hair cell plasma membrane fluidityChen G, Zhao H. Effects of intense noise exposure on the outer hair cell plasma membrane fluidity. Hearing Research 2006, 226: 14-21. PMID: 16870367, DOI: 10.1016/j.heares.2006.06.007.
- Prestin is expressed on the whole outer hair cell basolateral surfaceYu N, Zhu M, Zhao H. Prestin is expressed on the whole outer hair cell basolateral surface. Brain Research 2006, 1095: 51-58. PMID: 16709400, PMCID: PMC2548272, DOI: 10.1016/j.brainres.2006.04.017.
- Gap Junctions and Cochlear HomeostasisZhao H, Kikuchi T, Ngezahayo A, White T. Gap Junctions and Cochlear Homeostasis. The Journal Of Membrane Biology 2006, 209: 177. PMID: 16773501, PMCID: PMC1609193, DOI: 10.1007/s00232-005-0832-x.
- Gap junctional hemichannel-mediated ATP release and hearing controls in the inner earZhao H, Yu N, Fleming C. Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 18724-18729. PMID: 16344488, PMCID: PMC1317927, DOI: 10.1073/pnas.0506481102.
- Connexin26 is responsible for anionic molecule permeability in the cochlea for intercellular signalling and metabolic communicationsZhao H. Connexin26 is responsible for anionic molecule permeability in the cochlea for intercellular signalling and metabolic communications. European Journal Of Neuroscience 2005, 21: 1859-1868. PMID: 15869481, PMCID: PMC2548270, DOI: 10.1111/j.1460-9568.2005.04031.x.
- Paradoxical Enhancement of Active Cochlear Mechanics in Long-Term Administration of SalicylateHuang Z, Luo Y, Wu Z, Tao Z, Jones R, Zhao H. Paradoxical Enhancement of Active Cochlear Mechanics in Long-Term Administration of Salicylate. Journal Of Neurophysiology 2004, 93: 2053-2061. PMID: 15590729, DOI: 10.1152/jn.00959.2004.
- Excitation of fluorescent dyes inactivates the outer hair cell integral membrane motor protein prestin and betrays its lateral mobilitySantos-Sacchi J, Zhao HB. Excitation of fluorescent dyes inactivates the outer hair cell integral membrane motor protein prestin and betrays its lateral mobility. Pflügers Archiv - European Journal Of Physiology 2003, 446: 617-622. PMID: 12783229, DOI: 10.1007/s00424-003-1053-8.
- Long-term natural culture of cochlear sensory epithelia of guinea pigsZhao H. Long-term natural culture of cochlear sensory epithelia of guinea pigs. Neuroscience Letters 2001, 315: 73-76. PMID: 11711218, DOI: 10.1016/s0304-3940(01)02357-6.
- Chlorpromazine Alters Outer Hair Cell ElectromotilityLue A, Zhao H, Brownell W. Chlorpromazine Alters Outer Hair Cell Electromotility. Otolaryngology 2001, 125: 71-76. PMID: 11458218, DOI: 10.1067/mhn.2001.116446.
- Directional rectification of gap junctional voltage gating between Dieters cells in the inner ear of guinea pigZhao H. Directional rectification of gap junctional voltage gating between Dieters cells in the inner ear of guinea pig. Neuroscience Letters 2000, 296: 105-108. PMID: 11108992, DOI: 10.1016/s0304-3940(00)01626-8.
- Voltage Gating of Gap Junctions in Cochlear Supporting Cells: Evidence for Nonhomotypic ChannelsZhao H, Santos-Sacchi J. Voltage Gating of Gap Junctions in Cochlear Supporting Cells: Evidence for Nonhomotypic Channels. The Journal Of Membrane Biology 2000, 175: 17-24. PMID: 10811964, DOI: 10.1007/s002320001051.
- Voltage- and Tension-Dependent Lipid Mobility in the Outer Hair Cell Plasma MembraneOghalai J, Zhao H, Kutz J, Brownell W. Voltage- and Tension-Dependent Lipid Mobility in the Outer Hair Cell Plasma Membrane. Science 2000, 287: 658-661. PMID: 10650000, PMCID: PMC1976274, DOI: 10.1126/science.287.5453.658.
- Auditory collusion and a coupled couple of outer hair cellsZhao H, Santos-Sacchi J. Auditory collusion and a coupled couple of outer hair cells. Nature 1999, 399: 359-362. PMID: 10360573, DOI: 10.1038/20686.
- Effect of Membrane Tension on Gap Junctional Conductance of Supporting Cells in Corti's OrganZhao H, Santos-Sacchi J. Effect of Membrane Tension on Gap Junctional Conductance of Supporting Cells in Corti's Organ. The Journal Of General Physiology 1998, 112: 447-455. PMID: 9758863, PMCID: PMC2229429, DOI: 10.1085/jgp.112.4.447.