Research:

Mechanosensory hair cell loss is a leading cause of hearing and balance disorders.  Mutations in several hundred human genes result in hearing loss, with a frequency of ~1:500 for congenital hearing loss; progressive hearing loss is even more common, affecting 12% of the population.   We use the zebrafish lateral line system to study hair cells in vivo, using advanced imaging techniques to monitor their activity, and genome editing methods to manipulate their function.  Current research projects include:

Hair cell development:  Hair cells acquire a complex cellular architecture with specialized apical stereocilia that transduce mechanical signals and a rapid expansion of mitochondria.  We are interested in the genetic mechanisms that shape cellular differentiation.

Hair cell death:  Hair cells are susceptible to environmental insult, including noise damage and drug exposure.  We study the underlying vulnerability of hair cells to damage and are developing potential therapeutics to prevent this process.

Hair cell regeneration: In contrast to humans, zebrafish regenerate hair cells in response to damage.  We are interested in the identification of stem cell pools that contribute to regeneration and the genetic architecture that regulates their activation and maintenance.

Selected Publications:

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

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

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.

Suli, A., Watson, G.M., Rubel, E.W., Raible, D.W. (2012). Rheotaxis in larval zebrafish is mediated by lateral line mechanosensory hair cells. PLoS One, 7:e29727. PMCID:PMC3281009

Hailey, D.W., Roberts, B., Owens, K.N., Stewart, A.K., Linbo, T., Pujol, R., Alper, S.L., Rubel, E.W, Raible, D.W. (2012). Loss Slc4a1b Chloride/Bicarbonate Exchanger Function Protects Mechanosensory Hair Cells from Aminoglycoside Damage in the Zebrafish Mutant persephone. PLoS Genet 8(10): e1002971. PMCID: PMC3469417

Esterberg, R., Hailey, D.W., Coffin, A.B., Raible, D.W. and Rubel, E.W. (2013). Disruption of intracellular calcium is integral to aminoglycoside-induced hair cell death. J Neurosci., 33: 7513-7525. PMCID: PMC3703319

Stawicki, T.M., Owens, K.N., Linbo, T., Reinhart, K.E., Rubel, EW, Raible, D.W. (2014). The zebrafish merovingian mutant reveals a role for pH regulation in hair cell toxicity and function. Disease Models Mech., 7:847-56.

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

Thomas, E.D., Cruz, I.A., Hailey, D.W., and Raible D.W. (2015). There and back again: Development and regeneration of the zebrafish lateral line system. Wiley Interdiscip Rev Dev Biol. 4:1-16. PMCID: PMC4268111

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

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