Research

Hair cells of the inner ear act as mechanosensors, converting mechanical stimuli to electrical signals transmitted to the brain. Hair cells of the auditory organs respond to sound stimuli for hearing perception; those in the vestibular organs respond to gravity and head movements for perception of balance.

Hair cells are called such because they have actin-rich protrusions, stereocilia, at their apical end. Displacement of stereocilia opens ion channels resulting in depolarization and release of transmitter from synapses at the basal end of the cell to terminals of innervating afferent nerves.

Damage and loss of hair cells are leading causes of hearing and balance disorders, affecting over 40 million people in the US. Hair cells are susceptible to environmental insults, including noise, chemical exposure and accumulated damage during aging. Hair cell loss in humans is irreversible.

Zebrafish lateral line hair cells share many properties with those of the inner ear, and are sensitive to the same types of damaging agents as human cells. However they are able to regenerate hair cells throughout life. The location of the lateral line on the surface of the body allows access for visualization and manipulation.

We take an interdisciplinary approach to study hair cell development, death and regeneration that uses genetics, genome editing, single cell profiling, high resolution imaging, small molecule screening and computational modeling.

The Raible lab values equity and inclusion and strives to provide a welcoming environment for trainees from diverse backgrounds. We recognize that oppressive policies create barriers that prevent the entry and participation of underrepresented groups, hindering the advancement of science. We provide resources to empower trainees and support their progression throughout their scientific careers.

Preprints

Wu P, Barros Becker F, Ogelman R, Camci ED, Linbo TH, Simon JA, Rubel EW, Raible DW. Multiple mechanisms of aminoglycoside ototoxicity are distinguished by subcellular localization of action. bioRxiv 2024.05.30.596537

Recent Publications

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): dev202944.

Hewitt MN, Cruz IA, Linbo TH, Raible DW. Spherical harmonics analysis reveals cell shape-fate relationships in zebrafish lateral line neuromasts. Development. 2024 Mar 1;151(5):dev202839.

Bustad E, Mudrock E, Nilles EM, Mcquate A, Bergado M, Gu A, Galitan L, Gleason N, Ou HC, Raible DW, Hernandez RE, Ma S. In vivo screening for toxicity-modulating drug interactions identifies antagonism that protects against ototoxicity in zebrafish. Front Pharmacol. 2024 Mar 7;15:1363545.

McQuate A, Knecht S, Raible DW (2023) Activity regulates a cell type-specific mitochondrial phenotype in zebrafish lateral line hair cells. Elife. 2023 Mar 13;12:e80468.

Saunders LM, Srivatsan SR, Duran M, Dorrity MW, Ewing B, Linbo T, Shendure J, Raible DW, Moens CB, Kimelman D, Trapnell C. (2023) Deep molecular, cellular and temporal phenotyping of developmental perturbations at whole organism scale. Nature. 2023 Nov;623(7988):782-791.

Shi T, Beaulieu MO, Saunders LM, Fabian P, Trapnell C, Segil N, Crump JG, Raible DW. (2023) Single-cell transcriptomic profiling of the zebrafish inner ear reveals molecularly distinct hair cell and supporting cell subtypes. Elife. 2023 Jan 4;12:e82978.

Dorrity MW, Saunders LM, Duran M, Srivatsan SR, Barkan E, Jackson DL, Sattler SM, Ewing B, Queitsch C, Shendure J, Raible DW, Kimelman D, Trapnell C. Proteostasis governs differential temperature sensitivity across embryonic cell types. Cell. 2023 Nov 9;186(23):5015-5027.e12.

Smith ET, Sun P, Yu SK, Raible DW, Nicolson T. Differential expression of mechanotransduction complex genes in auditory/vestibular hair cells in zebrafish. Front Mol Neurosci. 2023 Nov 14;16:1274822.

Select Other Publications

Bellairs JA, Redila VA, Wu P, Tong L, Webster A, Simon JA, Rubel EW, Raible DW. An in vivo Biomarker to Characterize Ototoxic Compounds and Novel Protective Therapeutics. Front Mol Neurosci. 2022 Jul 18;15:944846. PMCID: PMC9342690

Kitcher SR, Kirkwood NK, Camci ED, Wu P, Gibson RM, Redila VA, Simon JA, Rubel EW, Raible DW, Richardson GP, Kros CJ. (2019). ORC-13661 protects sensory hair cells from aminoglycoside and cisplatin ototoxicity. JCI Insight. 4(15):e126764. PMCID: PMC6693895

Thomas ED, Raible DW. (2019). Distinct progenitor populations mediate regeneration in the zebrafish lateral line. Elife, 8. pii: e43736. PMCID: PMC6433462

Pickett SB, Thomas ED, Sebe J, Esterberg R, Linbo T, Hailey D, Raible DW. (2018). Cumulative mitochondrial activity confers selective susceptibility in active zebrafish mechanosensory hair cells. Elife, 7. pii: e38062. PMCID: PMC6345563

Chowdhury, S., Owens, K.N., Herr, J., Jiang, Q., Chen, X., Johnson, G., Groppi, V., Raible, D.W., Rubel, EW and Simon J.A. (2018). Phenotypic Optimization of Urea-Thiophene Carboxamides To Yield Potent, Well Tolerated, and Orally Active Protective Agents against Aminoglycoside-Induced Hearing Loss. J. Med. Chem., 2018 61(1):84-97. PMCID: PMC5889090

Sebe, J., Cho, S., Sheets, L., Rutherford, M., von Gersdorff, H., and Raible, D.W. (2017). Ca2+ permeable AMPARs mediate glutamatergic transmission and excitotoxic damage at the hair cell afferent synapse. J. Neurosci., 37:6162-6175.PMCID: PMC5481947

Hailey, DW, Esterberg R, Linbo T, Rubel, E.W. and Raible, D.W. (2017). Delivery of aminoglycoside antibiotics to the lysosomes predicts their toxicity in mechanosensory hair cells. J. Clinical Invest. 127(2):472-486.PMCID: PMC5272180

Esterberg R, Linbo T, Pickett SB, WuP, Ou HC, Rubel, E.W. and Raible, D.W. (2016). Mitochondrial calcium uptake underlies ROS generation during aminoglycoside-induced hair cell death. J. Clinical Invest., 126:3556-66. PMCID: PMC5004972

Stawicki TM, Hernandez L, Esterberg R, Linbo T, Owens KN, Shah AN, Thapa N, Roberts B, Moens CB, Rubel, E.W. and Raible, D.W. (2016). Cilia genes play differing roles in aminoglycoside-induced hair cell death in zebrafish. G3, 6:2225-35. PMCID: PMC4938675

Cruz, I.A., Kappedal, R., Mackenzie, S.M., Hailey, D.W., Hoffman, T.L., Schilling, T.F. and Raible, D.W. (2015). Robust regeneration of adult zebrafish lateral line hair cells reflects continued precursor pool maintenance. Dev. Biol., 402: 229-238. PMCID: PMC4450121

Esterberg, R., Hailey, D.W., Rubel, EW, and Raible, D.W. (2014). ER-mitochondrial calcium flow underlies vulnerability of mechanosensory hair cells to damage. J. Neurosci., 34:9703-9719. PMCID: PMC4099547

Ma, E.Y., Rubel, E.W and Raible, D.W. (2008). Notch signaling regulates the extent of hair cell regeneration in the zebrafish lateral line. J. Neurosci., 28: 2261-2273.

Owens, K.N., Santos, F., Roberts, B., Linbo, T., Knisely, A.J., Simon, J.A., Rubel, E.W and Raible, D.W. (2008). Identification of genetic and chemical modulators of zebrafish mechanosensory hair cell death. PLoS Genetics, 4: e1000020. PMCID: PMC2265478

Nechiporuk, A. and Raible, D.W. (2008). Fgf-dependent primordium organization drives lateral line segmentation in zebrafish. Science, 320:1774-1777.

My Bibliography on PubMed