THE OVERALL GOAL of our research program is to protect and regenerate the inner ear in order to improve patients’ hearing health. We strive to understand the mechanisms of development, regeneration, and protection of mammalian sensory hair cells using state-of-the-art technologies and collaborative approaches.


Hair cells are born and then precisely organized into rows, a highly-ordered structure critical for our hearing organ to function properly. Understanding how this complex organ develops provides us with invaluable insights into how inner ear malformation relates to congenital hearing loss and also expedites our efforts in regenerating this organ. Numerous signaling pathways including Wnt signaling have been implicated to regulate these critical developmental steps.

Our group is interested in determining how Wnt signaling dictates these diverse processes and interact with other key signaling pathways. In particular, we aim to probe individual components of the pathway to determine their roles in governing sensory cell fate and planar cell polarity.


Regenerating the mammalian cochlea is a monumental task yet it remains our ultimate goal. Our two-pronged approach is based on our findings that the newborn mouse cochlea and utricle both regenerate lost hair cells by defined progenitors.

By interrogating the genetic landscape of cochlear and utricular hair cell progenitors, we hope to better understand mechanisms governing early phases of regeneration. Using in vitro and in vivo models of hair cell regeneration in the utricle, we aim to characterize the mechanisms and physiology of vestibular regeneration at both the cellular and organ levels.

Aminoglycoside Ototoxicity

Aminoglycosides are potent antibiotics that cause irreversible hearing loss, making aminoglycoside ototoxicity one of the most preventable causes of hearing loss. We aim to design and build a new version of antibiotic that is non-ototoxic. In a collaborative effort with Tony Ricci’s lab, we have recently generated the first generation of non-ototoxic aminoglycoside derivatives. We now focus on understanding the structural-activity relationships of these compounds by studying their interactions with bacterial ribosomes, trafficking into bacteria and hair cells, antimicrobial activities and ototoxicity. With these information, we plan to optimize the next generation of drug design and synthesis.



Billings S, Myers N, Quiruz L, Cheng AG. (2021) Opposing effects of Wnt/beta-catenin signaling on epithelial and mesenchymal cell fate in the developing cochlea. Development 148 (11): dev199091.

Mao B, Wang Y, BalasubramanianT, Utrioste R, Wafa R, Fitzerald T, Haraczy S, Edwards-Hollingsworth K, Sayyid ZN, Wilder D, SajjaVSSS, Wei Y, Arun P, Gist I, Cheng AG, Long J, Kelley MW. (2021) Assessment of auditory and vestibular damage in a mouse model after single and triple blast exposures. Hear Res. 2021 Jun 7;407:108292. doi: 10.1016/j.heares.2021.108292.

Hirai T, Mayer A, Nobashi TW, Lin P-Y, Xiao Z, Udagawa T, Seo K, Simonetta F, Baker J, Cheng AG, Negrin RS, Gambhir SS. (2021) Imaging Alloreactive T Cells Provides Early Warning of Organ Transplant Rejection. JCI Insight 2021 Jul 8;6(13):145360.doi: 10.1172/jci.insight.145360.

Jan TA, Eltawil Y, Ling A, Chen L, Ellwanger DC, Heller S, Cheng AG. (2021) Single cell transcriptomics reveal spatiotemporal dynamics of inner ear sensory and non-sensory cells. Cell Rep. Jul 13;36(2):109358. doi: 10.1016/j.celrep.2021.109358.

Qian JZ, Alyono JC, Cheng AG Ahmad IA, Chang KW. Trends and Healthcare Use Following Different Cholesteatoma Surgery Types in a National Cohort, 2003-2019. (2021) Otol Neurotol 2021 Jul 23. doi: 10.1097/MAO.0000000000003284.

Sun H, Wang T, Atkinson PJ, Billings S, Dong W, Cheng AG. Gpr125 marks distinct cochlear cell types and is dispenable for cochlear development and function. (2021) Front Cell Dev BiolJul 28;9:690955. doi: 10.3389/fcell.2021.690955. eCollection 2021.

Qian JZ, Megwalu U, Cheng AG, Balakrishnan K. (2021) Outpatient Healthcare Use and Outcomes after Pediatric Tracheostomy. Int J Ped Otorhinolaryngol DOI: 10.1016/j.ijporl.2021.110963.

Moon P, Theruvath J, Chang J, Song Y, Shpanskaya K, Maleki M, Cheng AG, Ahmad I, Yeom K. (2021) MRI Correlates of Ototoxicity in the Auditory Pathway of Children Treated for Medulloblastoma. Otol Neurotol doi: 10.1097/MAO.0000000000003336.

Udagawa T, Atkinson PJ, Milon B, Abitbol JM, Song Y, Sperber M, Huarcaya-Najarro E, Scheibinger M, Elton R, Hertzano R, Cheng AG. (2021) Lineage-tracing and translatomic analysis of damage inducible mitotic cochlear progenitors identifies candidate genes regulating regeneration. PLoS Biol Nov 10;19(11):e3001445.doi: 10.1371/journal.pbio.3001445.

Aaron KA, Hosseini D, Vaisbuch Y, Scheibinger M,Grillet N, Heller S, Wang T, Cheng AG. (2021) Selection Criteria Optimal for Recovery of Inner Ear Tissues from Deceased Organ Donors. Otol Neurotol (in press).

Vaisbuch Y, Hosseini DK, Wagner A, Hirt B, Mueller M, Heller S, Cheng AG, Löwenheim H, Aaron KA. (2021) A Novel Resource and Surgical Approach for Human Inner Ear Tissues from Organ and Tissue Donors. Otol Neurotol (in press).


Qian JZ, Alyono JC, Lin MC, Cooperman SP, Cheng AG, Balakrishnan K. (2021) Opioid prescribing patterns following pediatric tonsillectomy in the United States, 2009-2017. Laryngoscope 2020 Oct 7. doi: 10.1002/lary.29159. PMCID: PMC7334366

Qian JZ, Chang KW, Ahmad IA, Tribble M, Cheng AG. (2021) Utilization of Diagnostic Testing and Treatment for Sensorineural Hearing Loss in Children, United States 2008-2018. JAMA Otolaryngol-HNS 2020 Dec 30. doi: 10.1001/jamaoto.2020.5030

Denoyelle F, Simon F, Chang KW, Chan KH, Cheng AG, Cheng AT, Choo DI, Daniel SJ, Farinetti A, Garabedian E-N, Greinwald JH, Hoff SR, Hone S, Licameli GR, Papsin BC, Poe DS, Pransky S, Smith RJH, Triglia J-M, Walton J, Zalzal G, Leboulander N. (2020) International Pediatric Otolaryngology Group (IPOG) Consensus Recommendations: Congenital Cholesteatoma. Otol Neurotol 2020 Mar;41(3):345-351 doi: 10.1097/MAO.00000000000002521.

Moon P, Qian J, McKenna E, Rowe N, Xi K, Ng N, Tam L, MacEchern S, Zheng J, Ahmad I, Cheng AG, Forkert N, Yeom K. Cerebral volume and diffusion MRI changes in children with sensorineural hearing loss. NeuroImage: Clinical Jun 25;27:102328. doi: 10.1016/j.nicl.2020.102328.

Sayyid ZS, Boldt B, Mokhtari T, Kiyosaki K, Yeom KW, Cheng AG. Congenital Hearing Loss is Associated with a High Incidence of Central Nervous System Abnormalities. Otol Neurotol. doi: 1097/MAO.0000000000002778

Aaron KA, Kim GS, Cheng AG  Advances in Inner Ear Therapeutics for Hearing Loss in Children. Curr Otorhinolaryngol Rep8, 285–294.

Trieu V, Hosseini D, Kim GS, Truong MT, Cheng AG  Congenital Orocutaneous Fistula Associated with Ectopic Salivary Glands and Submandibular Gland Aplasia. Laryngoscope

Huarcaya-Najarro E, Huang J, Quiruz L, Jacobo A, Grillet N, Cheng AG.  Dual regulation of planar polarization by Wnt secretion and Vangl2 in the developing mouse cochlea. Development 2020 Sep 9;dev.191981. doi: 10.1242/dev.191981.

Qian JZ, Alyono JC, Lin MC, Cooperman SP, Cheng AG, Balakrishnan K. Opioid prescribing patterns following pediatric tonsillectomy in the United States, 2009-2017. Laryngoscope 2020 Oct 7. doi: 10.1002/lary.29159.

O’Sullivan M, Song Y, Greenhouse R, Lin R, Perez A, MacDonald JP, Siddiqui Z, Lagasca D, Comstock K, Huth ME, Cheng AG, Ricci AJ. Dissociating Antibacterial from Ototoxic Effects of Gentamicin C-subtypes. Proc Natl Acad Sci USA 2020 Dec 7;202013065.doi: 10.1073/pnas.2013065117.


Jansson L, Ebeid M, Shen J, Mokhtari T, Quiruz L, Ornitz D, Huh SH, Cheng AG. Beta-catenin is required for radial cell patterning and identity in the developing mouse cochlea. Proc Natl Acad Sci USA. Oct 15;116(42):21054-21060. doi: 10.1073/pnas.1910223116.

Atkinson PJ, Kim GS, Cheng AG. Direct cellular reprogramming and inner ear regeneration. Expert Opin on Biol Ther1080/14712598.2019.1564035.

Wang T, Niwa M, Sayyid ZN, Hosseini D, Pham N, Jones SM, Ricci AJ, Cheng AG. Uncoordinated maturation of developing and regenerating mammalian vestibular hair cells. PLoS Biol Jul 1;17(7):e3000326. doi: 10.1371/journal.pbio.3000326. eCollection 2019 Jul.

Sayyid ZN, Wang T, Chen L, Jones SM, Cheng AG. Atoh1 directs regeneration and functional recovery in the mature mouse utricle. Cell Rep org/10.1016/j.celrep.2019.06.028.


Atkinson P, Dong Y, Gu S, Liu W, Huarcaya Najarro E, Udagawa T, Cheng AG. Sox2 haploinsufficiency primes regeneration in the mouse cochlea. J Clin Invest. Apr 2;128(4):1641-1656. doi: 10.1172/JCI97248

Sayyid ZN, Kim GS, Cheng AG. Molecular therapy for genetic and degenerative vestibular disorders. Curr Opin Otolaryngol Head and Neck Surg doi: 10.1097/MOO.0000000000000477.

O’Sullivan M, Poitevin, F, Sierra RG, Gati C, Dao EH, Rao Y, Aksit F, Ciftci H, Corcepius N, Hayes B, Hunter M, Liang M, McGurk A, Mbgam P, Obrinsky T, Pardo F, Seaberg M, Cheng AG, Ricci AJ, DeMirci H. Aminoglycoside ribosome interactions reveal novel conformational states at ambient temperature. Nucleic Acids Res doi: 10.1093/nar/gky693.


Towards the prevention of aminoglycoside-related hearing loss. O’Sullivan M, Perez A, Lin R, Sajjadi A, Ricci AJ, Cheng AG. Front Cell Neurosci. 2017 Oct 18;11:325. doi: 10.3389/fncel.2017.00325.

Mind your ears: a new antidote to aminoglycoside toxicity? O’Sullivan M and Cheng AG. J Med Chem. doi: 10.1021/acs.jmedchem.7b01645.


Profiling specific inner ear cell types using cell sorting techniques. Jan TA, Jansson L, Atkinson PJ, Wang T, Cheng AG. Methods Mol Biol 1427:431-45. doi: 10.1007/978-1-4939-3615-1_23.


Protein-engineered hydrogel encapsulation for 3D culture of murine cochlea. Chang DT, Chai R, Dimarco R, Heilshorn SC, Cheng AG. Otol Neurotol 36(3):531-8 doi: 10.1097/MAO.0000000000000518.

Designer aminoglycosides prevent cochlear hair cell loss and hearing loss. Huth M, Han KH, Soutadeh K, Hsieh YJ, Effertz T, Vu AA, Verhoeven S, Hsieh MH, Greenhouse RJ, Cheng AG, Ricci AJ. J Clin Invest pii: 77424. doi: 10.1172/JCI77424.

Lgr5+ cells regenerate hair cells via proliferation and direct transdifferentiation in damaged neonatal mouse utricle. Wang T, Chai R, Kim GS, Pham N, Jansson L, Nguyen DQ, Kuo B, May LA, Zuo J, Cunningham LL, Cheng AG. Nat Commun 6:6613. doi: 10.1038/ncomms7613.

Intraoperative acupuncture for posttonsillectomy pain: A randomized, double-blind, placebo-controlled trial. Tsao GJ, Messner AH, Seybold J, Sayyid ZN, Cheng AG, Golianu B. Laryngoscope doi: 10.1002/lary.25252.

Making sense of Wnt signaling—linking hair cell regeneration to development. Jansson L, Kim GS, Cheng AG.  Front Cell Neurosci 9:66. doi: 10.3389/fncel.2015.00066.

Sensory cell development and regeneration: similarities and differences. Atkinson PJ, Huarcaya Najarro E, Sayyid ZN, Cheng AG. Development 142(9), 1561-1571 doi:10.1242/dev.114926.


Spontaneous hair cell regeneration in the neonatal mouse cochlea in vivo. Cox BC, Chai R, Lenoir A, Liu Z, Zhang LL, Nguyen DH, Chalasani K, Steigelman KA, Fang J, Cheng AG, Zuo J. Development 141: 816-829 doi:10.1242/dev.103036.


Transient, afferent input-dependent, postnatal niche for neural progenitor cells in the cochlear nucleus. Volkenstein S, Oshima K, Sinkkonen ST, Corrales CE, Most SP, Chai R, Jan TA, Cheng AG, Heller S. Proc Natl Acad Sci U S A. 2013; Aug 27; 110(35):14456-61.

A simple method for purification of vestibular hair cells and non-sensory cells, and application for proteomic analysis.Herget M, Scheibinger M, Guo Z, Jan TA, Adams CM, Cheng AG, Heller S. PLoS One. 2013 Jun 4;8(6):e66026.

Integrity and regeneration of mechanotransduction machinery regulate aminoglycoside entry and sensory cell death. Vu AA, Nadaraja GS, Huth ME, Luk L, Kim J, Chai R, Ricci AJ, Cheng AG. PLoS One. 2013; 8 (1): e54794

Tympanic border cells are Wnt-responsive and can act as progenitors for postnatal mouse cochlear cells. Jan TA, Chai R, Sayyid ZN, van Amerongen R, Xia A, Wang T, Sinkkonen ST, Zeng YA, Levin JR, Heller S, Nusse R, Cheng AG. Development. 2013; 140 (6): 1196-206


Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea. Chai R, Kuo B, Wang T, Liaw EJ, Xia A, Jan TA, Liu Z, Taketo MM, Oghalai JS, Nusse R, Zuo J, Cheng AG. Proc Natl Acad Sci U S A. 2012; 109 (21): 8167-72


Dynamic expression of Lgr5, a Wnt target gene, in the developing and mature mouse cochlea. Chai R, Xia A, Wang T, Jan TA, Hayashi T, Bermingham-McDonogh O, Cheng AG. J Assoc Res Otolaryngol. 2011; 12 (4): 455-69

Functional hair cell mechanotransducer channels are required for aminoglycoside ototoxicity. Alharazneh A, Luk L, Huth M, Monfared A, Steyger PS, Cheng AG, Ricci AJ. PLoS One. 2011; 6 (7): e22347

Intrinsic regenerative potential of murine cochlear supporting cells. Sinkkonen ST, Chai R, Jan, T, Hartman B, Laske R, Gahlen F, Sinkkonen W, Cheng AG, Oshima K, Heller. Scientific Reports. 2011; 1 (26): DOI:10.1038/srep0002

Isolating LacZ-expressing cells from mouse inner ear tissues using flow cytometry. Jan TA, Chai R, Sayyid ZN, Cheng AG. J Vis Exp. 2011; (58): e3432

Mechanisms of aminoglycoside ototoxicity and targets of hair cell protection. Huth ME, Ricci AJ, Cheng AG. Int J Otolaryngol. 2011: 2011 937861