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Department of Cell Biology Faculty
Richard Kollmar, Ph.D.
Tel: (718) 221-6559 • Fax: (718) 270-3732
Morphogenesis and Regeneration in the Inner Ear
Our goal is to understand the physiology and pathology of the auditory and vestibular periphery at the molecular level.
First, we are studying the molecular genetics of otolith formation in the zebrafish, Danio rerio. By combining proteomics, molecular biology, and embryology, we are identifying novel otolith proteins and dissecting their function in biomineralization. Recently, we have used a cross-species shotgun proteomics approach to identify three novel otolith proteins, precerebellin, neuroserpin, and Sparc (osteonectin). Furthermore, we have demonstrated that Sparc, a key bone protein, is required for normal otolith growth. To extend these studies, we are now elucidating the interplay between genetic networks and physiological activity that underlies the control of otolith morphogenesis. These studies in a tractable animal model will help us to understand the otoconial defects associated with common vestibular deficits in humans.
Second, we are studying the regeneration of damaged spiral ganglion neurons in mice. By using a noise-exposure paradigm and microarray hybridization, we have identified Wnt-Frizzled signaling as a candidate pathway to stimulate neurite outgrowth. We have also established a culture protocol for adult spiral ganglion neurons. By using bulk- and choice-based in vitro assays, we are now testing agents that can activate the Wnt-Frizzled pathway and guide regenerating neurites. These studies are laying the foundation for future in vivo experiments and ultimately the engineering of better cochlear implants.
Shah, S.M., Kang, Y.-J., Christensen, B.L., Feng, A.S., Kollmar, R. 2009. Expression of Wnt Receptors in Adult Spiral Ganglion Neurons: Frizzled 9 Localization at Growth Cones of Regenerating Neurites. Neuroscience, in press. [Abstract] [Manuscript available at http://hdl.handle.net/2142/14823]
Kang, Y.-J., Stevenson, A.K., Yau. P.M., Kollmar, R. 2008. Sparc Protein Is Required for Normal Growth of Zebrafish Otoliths. J. Assoc. Res. Otolaryngol., 9:436-51. [Abstract][Manuscript available at http://hdl.handle.net/2142/9575]
Vieira, M., Christensen, B.L., Wheeler, B.C., Feng, A.S., Kollmar, R. 2007. Survival and stimulation of neurite outgrowth in a serum-free culture of spiral ganglion neurons from adult mice. Hear. Res., 230:17-23. [Abstract] [Manuscript available at http://hdl.handle.net/2142/1353]
Asai, Y., Chan, D.K., Starr, C.J., Kappler, J.A., Kollmar, R., and Hudspeth, A.J. 2006. Mutation of the atrophin2 gene in the zebrafish disrupts signaling by fibroblast growth factor during development of the inner ear. Proc. Natl. Acad. Sci. USA, 103:9069-74. [Abstract]
Lopez-Schier, H., Starr, C.J., Kappler, J.A., Kollmar, R., and Hudspeth, A.J. 2004. Directional cell migration establishes the axes of planar polarity in the posterior lateral-line organ of the zebrafish. Dev. Cell, 7:401-12. [Abstract]
Kappler, J.A., Starr, C.J., Chan, D.K., Kollmar, R., and Hudspeth, A.J. 2004. A nonsense mutation in the gene encoding a zebrafish myosin VI isoform causes defects in hair-cell mechanotransduction. Proc. Natl. Acad. Sci. USA., 101:13056-61. [Abstract]
Starr, C.J., Kappler, J.A., Chan, D.K., Kollmar, R., and Hudspeth, A.J. 2004. Mutation of the zebrafish choroideremia gene encoding Rab escort protein 1 devastates hair cells. Proc. Natl. Acad. Sci. USA., 101:2572-7. [Abstract]
Kollmar, R., Nakamura, S.K., Kappler, J.A., and Hudspeth, A.J. 2001. Expression and phylogeny of claudins in vertebrate primordia. Proc. Natl. Acad. Sci. USA., 98(18): 10196-201. [Abstract]
Kollmar, R. 1999. Who does the hair cell's 'do? Rho GTPases and hair-bundle morphogenesis. Curr. Opin. Neurobiol., 9(4): 394-8. [Abstract]
Kollmar, R., Fak, J., Montgomery, L.G., and Hudspeth, A.J. 1997. Hair cell-specific splicing of mRNA for the alpha1D subunit of voltage-gated Ca2+ channels in the chicken's cochlea. Proc. Natl. Acad. Sci. USA., 94(26): 14889-93. [Abstract]