Hearing Restoration Project Papers

Publications resulting from Hearing Restoration Project research funding, with select lay summaries.

2025

• Lush ME, Tsai YY, Chen S, et al. Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes. Nat Commun. 2025;16:5913. doi:10.1038/s41467-025-60251-0

  • Summary: Zebrafish Gene Discovery Reveals Clues for Hearing Restoration

• Miranda Portillo LS, Huang AP, Hosamani IV, Sanchez CN, Heller S, Benkafadar N. Anatomical and molecular insights into avian inner ear sensory hair cell regeneration. Dev Biol. 2025;525:13-25. doi:10.1016/j.ydbio.2025.05.021

• Summary: What Birds Teach Us About Restoring Hearing

• Sandler JE, Tsai YY, Chen S, et al. prdm1a drives a fate switch between hair cells of different mechanosensory organs. Nat Commun. 2025;16(1):7662. doi:10.1038/s41467-025-62942-0

• Summary: Zebrafish Study Reveals a Genetic Switch Controlling Ear and Balance Cells

• Seist R, Copeland JS, Tao L, Groves AK. Rational design of a Lfng-enhancer AAV construct drives specific and efficient gene expression in inner ear supporting cells. Hearing Research. 2025;458:109203. doi:10.1016/j.heares.2025.109203

• Summary: A New Tool for Targeting Only Supporting Cells in the Inner Ear

2024

• Beaulieu MO, Thomas ED, Raible DW. Transdifferentiation is temporally uncoupled from progenitor pool expansion during hair cell regeneration in the zebrafish inner ear. Development. 2024;151(15):dev.202944. doi:10.1242/dev.202944

• Summary: A Dual Method for Inner Ear Hair Cell Regrowth in Zebrafish

• Benkafadar N, Sato MP, Ling AH, et al. An essential signaling cascade for avian auditory hair cell regeneration. Developmental Cell. 2024;59(2):280-291.e5. doi:10.1016/j.devcel.2023.11.028

• Summary: An Essential Signaling Cascade for Hair Cell Regeneration in Birds

• Brigande JV. Otoferlin gene therapy restores hearing in deaf children. Molecular Therapy. 2024;32(4):859-860. doi:10.1016/j.ymthe.2024.03.020

• Gwilliam K, Sperber M, Perry K, et al. A cell type–specific approach to elucidate the role of miR-96 in inner ear hair cells. Front Audiol Otol. 2024;2:1400576. doi:10.3389/fauot.2024.1400576

• Summary: A Cell Type–Specific Approach to Detail the Role of a Small Molecule in Hair Cells

• Hewitt MN, Cruz IA, Raible DW. Spherical harmonics analysis reveals cell shape-fate relationships in zebrafish lateral line neuromasts. Development. 2024;151(2):dev.202251. doi:10.1242/dev.202251

• Summary: Mathematical Analysis of Zebrafish Cell Shape Shows Connection With Cell Function

• Liu Y, Yang L, Singh S, et al. Combinatorial Atoh1, Gfi1, Pou4f3, and Six1 gene transfer induces hair cell regeneration in the flat epithelium of mature guinea pigs. Hearing Research. 2024;441:108916. doi:10.1016/j.heares.2023.108916

• Summary: Combination of Four Genes May Help Regrow New Auditory Hair Cells in Mammals

• Maraslioglu-Sperber A, Blanc F, Heller S, Benkafadar N. Hyperosmotic sisomicin infusion: a mouse model for hearing loss. Sci Rep. 2024;14:15903. doi:10.1038/s41598-024-66635-4

• Summary: A New Mouse Model for Hearing Loss

• McGovern MM, Ghosh S, Dupuis C, Walters BJ, Groves AK. Reprogramming with Atoh1, Gfi1, and Pou4f3 promotes hair cell regeneration in the adult organ of Corti. PNAS Nexus. 2024;3(10):pgae445. doi:10.1093/pnasnexus/pgae445

• Summary: Genetic Reprogramming Regenerates Lost Hair Cells in the Mature Mouse Inner Ear

• McGovern MM, Hosamani IV, Niu Y, Nguyen KY, Zong C, Groves AK. Expression of Atoh1, Gfi1, and Pou4f3 in the mature cochlea reprograms nonsensory cells into hair cells. Proceedings of the National Academy of Sciences. 2024;121(5):e2304680121. doi:10.1073/pnas.2304680121

• Summary: Genetic Reprogramming Converts Nonsensory Cells into Sensory Cells in the Mature Cochlea

• Sato MP, Benkafadar N, Heller S. Hair cell regeneration, reinnervation, and restoration of hearing thresholds in the avian hearing organ. Cell Reports. 2024;43(3):113822. doi:10.1016/j.celrep.2024.113822

• Summary: Regrowing Hair Cells and Nerve Connections to Restore Hearing in Birds

• Sato MP, Huang AP, Heller S, Benkafadar N. Protocol for in vivo elimination of avian auditory hair cells, multiplexed mRNA detection, immunohistochemistry, and S-phase labeling. STAR Protocols. 2024;5(2):103118. doi:10.1016/j.xpro.2024.103118

• Summary: A Protocol for Investigating Hair Cell Regeneration in Birds

• Shi T, Kim Y, Llamas J, et al. Long-range Atoh1 enhancers maintain competency for hair cell regeneration in the inner ear. Proceedings of the National Academy of Sciences. 2024;121(51):e2418098121. doi:10.1073/pnas.2418098121

• Summary: Study Identifies Gene Regulators Behind Hearing Regeneration

2023

• Cox BC, Brigande JV, Walters BJ. Genetic and Epigenetic Strategies for Promoting Hair Cell Regeneration in the Mature Mammalian Inner Ear. In: Warchol ME, Stone JS, Coffin AB, Popper AN, Fay RR, eds. Hair Cell Regeneration. Springer Handbook of Auditory Research. Springer International Publishing; 2023:195-229. doi:10.1007/978-3-031-20661-0_8

• Kalra G, Lenz D, Abdul-Aziz D, et al. Cochlear organoids reveal transcriptional programs of postnatal hair cell differentiation from supporting cells. Cell Reports. 2023;42(11):113421. doi:10.1016/j.celrep.2023.113421

• Summary: Cochlear Organoids Reveal How Supporting Cells Differentiate Into Hair Cells

• Nguyen JD, Llamas J, Shi T, Crump JG, Groves AK, Segil N. DNA methylation in the mouse cochlea promotes maturation of supporting cells and contributes to the failure of hair cell regeneration. Proceedings of the National Academy of Sciences. 2023;120(33):e2300839120. doi:10.1073/pnas.2300839120

• Summary: Mouse Studies Tune Into Hearing Regeneration

• Shi T, Beaulieu MO, Saunders LM, et al. Single-cell transcriptomic profiling of the zebrafish inner ear reveals molecularly distinct hair cell and supporting cell subtypes. Elife. 2023;12:e82978. doi:10.7554/eLife.82978

• Wang X, Llamas J, Trecek T, et al. SoxC transcription factors shape the epigenetic landscape to establish competence for sensory differentiation in the mammalian organ of Corti. Proceedings of the National Academy of Sciences. 2023;120(34):e2301301120. doi:10.1073/pnas.2301301120

• Summary: Mouse Studies Tune Into Hearing Regeneration

2022

• Iyer AA, Hosamani I, Nguyen JD, et al. Cellular reprogramming with ATOH1, GFI1, and POU4F3 implicate epigenetic changes and cell-cell signaling as obstacles to hair cell regeneration in mature mammals. eLife. 2022;11:e79712. doi:10.7554/eLife.79712

• Summary: Molecular Barriers to Overcome for Hair Cell Regeneration in the Adult Mouse Cochlea

• Janesick A, Scheibinger M, Benkafadar N, Kirti S, Heller S. Avian auditory hair cell regeneration is accompanied by JAK/STAT-dependent expression of immune-related genes in supporting cells. Development. 2022;149(8):dev.200113. doi:10.1242/dev.200113

• Summary: Increasing Our Understanding of Avian Hair Cell Regeneration

• Janesick A, Scheibinger M, Heller S. Molecular Tools to Study Regeneration of the Avian Cochlea and Utricle. In: Groves AK, ed. Developmental, Physiological, and Functional Neurobiology of the Inner Ear. Neuromethods. Springer US; 2022:77-97. doi:10.1007/978-1-0716-2022-9_5

• Hertzano R, Mahurkar A. Advancing discovery in hearing research via biologist-friendly access to multi-omic data. Hum Genet. 2022;141(3-4):319-322. doi:10.1007/s00439-022-02445-w

• Summary: Advancing Discoveries via Biologist-Friendly Access to Multi-Omic Data

• Scheibinger M, Janesick A, Benkafadar N, Ellwanger DC, Jan TA, Heller S. Cell-type identity of the avian utricle. Cell Reports. 2022;40(13). doi:10.1016/j.celrep.2022.111432

• Summary: Cell-Type Identity of the Chick Balance Organ

• Trpchevska N, Freidin MB, Broer L, et al. Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss. The American Journal of Human Genetics. 2022;109(6):1077-1091. doi:10.1016/j.ajhg.2022.04.010

• Summary: Hope for Treatments Against Hearing Loss as 10 New Genes Identified

2021

• Benkafadar N, Janesick A, Scheibinger M, Ling AH, Jan TA, Heller S. Transcriptomic characterization of dying hair cells in the avian cochlea. Cell Reports. 2021;34(12). doi:10.1016/j.celrep.2021.108902

• Summary: Several Novel Findings Describing Cochlear Hair Cell Regeneration in Birds

• BRAIN Initiative Cell Census Network (BICCN). A multimodal cell census and atlas of the mammalian primary motor cortex. Nature. 2021;598(7879):86-102. doi:10.1038/s41586-021-03950-0

• Summary: A Multimodal Cell Census and Atlas of the Mammalian Primary Motor Cortex

• Hertzano R, Gwilliam K, Rose K, Milon B, Matern MS. Cell Type–Specific Expression Analysis of the Inner Ear: A Technical Report. The Laryngoscope. 2021;131(S5):S1-S16. doi:10.1002/lary.28765

• Summary: Tinnitus and Noise Trauma to the Inner Ear

• Janesick A, Scheibinger M, Benkafadar N, Kirti S, Ellwanger DC, Heller S. Cell-type identity of the avian cochlea. Cell Reports. 2021;34(12):108900. doi:10.1016/j.celrep.2021.108900

• Summary: Several Novel Findings Describing Cochlear Hair Cell Regeneration in Birds

• Kubota M, Scheibinger M, Jan TA, Heller S. Greater epithelial ridge cells are the principal organoid-forming progenitors of the mouse cochlea. Cell Reports. 2021;34(3). doi:10.1016/j.celrep.2020.108646

• Summary: Specific Group of Cochlear Cells in Mice Demonstrate Regenerative Potential

• Kubota M, Heller S. Murine cochlear cell sorting and cell-type-specific organoid culture. STAR Protocols. 2021;2(3):100645. doi:10.1016/j.xpro.2021.100645

• Summary: Specific Group of Cochlear Cells in Mice Demonstrate Regenerative Potential

• Milon B, Shulman ED, So KS, et al. A cell-type-specific atlas of the inner ear transcriptional response to acoustic trauma. Cell Reports. 2021;36(13). doi:10.1016/j.celrep.2021.109758

• Summary: Understanding Hearing Loss From Noise Damage Through Gene Expression Changes

• Orvis J, Gottfried B, Kancherla J, et al. gEAR: Gene Expression Analysis Resource portal for community-driven, multi-omic data exploration. Nat Methods. 2021;18(8):843-844. doi:10.1038/s41592-021-01200-9

• Summary: New High-Tech Portal Launched to Speed Innovations to Reverse Hearing Loss

• Tao L, Yu HV, Llamas J, et al. Enhancer decommissioning imposes an epigenetic barrier to sensory hair cell regeneration. Developmental Cell. 2021;56(17):2471-2485. doi:10.1016/j.devcel.2021.07.003

• Summary: The Latent Regenerative Potential of the Inner Ear

• Yao Z, Liu H, Xie F, et al. A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex. Nature. 2021;598(7879):103-110. doi:10.1038/s41586-021-03500-8

• Yu HV, Tao L, Llamas J, et al. POU4F3 pioneer activity enables ATOH1 to drive diverse mechanoreceptor differentiation through a feed-forward epigenetic mechanism. Proceedings of the National Academy of Sciences. 2021;118(29). doi:10.1073/pnas.2105137118

• Summary: A Common Ancestor for Cells Involved in Hearing and Touch

2020

• Gnedeva K, Wang X, McGovern MM, et al. Organ of Corti size is governed by Yap/Tead-mediated progenitor self-renewal. Proceedings of the National Academy of Sciences. 2020;117(24):13552-13561. doi:10.1073/pnas.2000175117

• Summary: USC Stem Cell Study Shows When to Quit “Yapping”

• Kolla L, Kelly MC, Mann ZF, et al. Characterization of the development of the mouse cochlear epithelium at the single cell level. Nat Commun. 2020;11(1):1-16. doi:10.1038/s41467-020-16113-y

• Summary: Study Charts Developmental Map of Inner Ear Sound Sensor in Mice

• Wan L, Lovett M, Warchol ME, Stone JS. Vascular endothelial growth factor is required for regeneration of auditory hair cells in the avian inner ear. Hear Res. 2020;385:107839. doi:10.1016/j.heares.2019.107839

• Summary: A Key Molecule Required for the Regeneration of Auditory Hair Cells in the Avian Inner Ear

2019

• Dunbar LA, Patni P, Aguilar C, et al. Clarin-2 is essential for hearing by maintaining stereocilia integrity and function. EMBO Molecular Medicine. 2019;11(9):e10288. doi:10.15252/emmm.201910288

• Zhu Y, Scheibinger M, Ellwanger DC, et al. Single-cell proteomics reveals changes in expression during hair-cell development. Kelley MW, ed. eLife. 2019;8:e50777. doi:10.7554/eLife.50777

2017

• Brigande JV. Hearing in the mouse of Usher. Nat Biotechnol. 2017;35(3):216-218. doi:10.1038/nbt.3815

• Summary: John Brigande provides commentary: Hearing in the mouse of Usher

2016

• Abdolazimi Y, Stojanova Z, Segil N. Selection of cell fate in the organ of Corti involves the integration of Hes/Hey signaling at the Atoh1 promoter. Development. 2016;143(5):841-850. doi:10.1242/dev.129320

• Geng R, Noda T, Mulvaney JF, Lin VYW, Edge ASB, Dabdoub A. Comprehensive Expression of Wnt Signaling Pathway Genes during Development and Maturation of the Mouse Cochlea. Riley BB, ed. PLoS ONE. 2016;11(2):e0148339. doi:10.1371/journal.pone.0148339

• Summary: Unraveling Genes Critical for Inner Ear Development

• Kempfle JS, Turban JL, Edge ASB. Sox2 in the differentiation of cochlear progenitor cells. Sci Rep. 2016;6. doi:10.1038/srep23293

• Summary: How Genes Interact to Produce Hair Cells

• Maass JC, Gu R, Cai T, et al. Transcriptomic Analysis of Mouse Cochlear Supporting Cell Maturation Reveals Large-Scale Changes in Notch Responsiveness Prior to the Onset of Hearing. Reh TA, ed. PLoS ONE. 2016;11(12):e0167286. doi:10.1371/journal.pone.0167286

• Suli A, Pujol R, Cunningham DE, et al. Innervation regulates synaptic ribbons in lateral line mechanosensory hair cells. J Cell Sci. 2016;129(11):2250-2260. doi:10.1242/jcs.182592

2015

• Maass JC, Gu R, Basch ML, et al. Changes in the regulation of the Notch signaling pathway are temporally correlated with regenerative failure in the mouse cochlea. Front Cell Neurosci. 2015;9. doi:10.3389/fncel.2015.00110

• Romero-Carvajal A, Navajas Acedo J, Jiang L, et al. Regeneration of Sensory Hair Cells Requires Localized Interactions between the Notch and Wnt Pathways. Developmental Cell. 2015;34(3):267-282. doi:10.1016/j.devcel.2015.05.025

• Stojanova ZP, Kwan T, Segil N. Epigenetic regulation of Atoh1 guides hair cell development in the mammalian cochlea. Development. 2015;142(20):3529-3536. doi:10.1242/dev.126763

• Waldhaus J, Durruthy-Durruthy R, Heller S. Quantitative High-Resolution Cellular Map of the Organ of Corti. Cell Reports. 2015;11(9):1385-1399. doi:10.1016/j.celrep.2015.04.062

• Tao L, Segil N. Early transcriptional response to aminoglycoside antibiotic suggests alternate pathways leading to apoptosis in sensory hair cells in the mouse inner ear. Front Cell Neurosci. 2015;9. doi:10.3389/fncel.2015.00190

• Tong L, Strong MK, Kaur T, et al. Selective deletion of cochlear hair cells causes rapid age-dependent changes in spiral ganglion and cochlear nucleus neurons. J Neurosci. 2015;35(20):7878-7891. doi:10.1523/JNEUROSCI.2179-14.2015

2014

• Micucci JA, Layman WS, Hurd EA, et al. CHD7 and retinoic acid signaling cooperate to regulate neural stem cell and inner ear development in mouse models of CHARGE syndrome. Human Molecular Genetics. 2014;23(2):434-448. doi:10.1093/hmg/ddt435