Research Abstract:
My lab studies the development and regeneration of sensory receptors in the inner ear. The loss of sensory hair cells from the human ear can lead to permanent deficits in hearing and balance. In contrast, the cochlea and vestibular organs of nonmammalian vertebrates have a robust capacity to regenerate sensory hair cells, and we hope to understand the basic biology of this regenerative process. Replacement hair cells are generated through a mechanism that involves the proliferation of progenitors (supporting cells) within the sensory epithelia. Our recent work has shown that N-cadherin interactions as well as signaling through the Jun kinase (JNK) pathway are key regulators of cell cycle entry in supporting cells. We are also studying the roles of the GATA3 and PAX2 transcription factors in the re-establishment of phenotypic patterning and innervation during regeneration. Finally, in collaboration with colleagues in the Department of Genetics, we are undertaking a large-scale screen of gene expression during the early stages of regeneration in the avian ear. Based on the results of this study, we are using siRNA techniques to investigate the role of specific genes in regenerative proliferation.
Selected Publications:
Matsui JI, Gale JE, Warchol ME. Critical signaling events in the aminoglycoside-induced of sensory hair cells in vitro.J Neurobiol 2004 61:250-266.
Matsui JI, HaqueA, Huss D, et al.. Caspase inhibitors promote vestibular hair cell function and survival following aminoglycoside treatment in vivo. J Neurosci 2003 23: 6111-6122.
Hawkins DR, Bashiardes S, Helms CA, et al. Gene Expression differences in quiescent versus regenerating hair cells of avian sensory epithelia: Implications for human hearing and balance disorders. Hum Mol Genet 2003 12:1261-1272.
Matsui JI, Ogilvie JM, Warchol ME. Inhibition of caspases prevents ototoxic and ongoing hair cell death. J Neurosci 2002 22:1218-1227.
Warchol ME. Cell density and N-cadherin interactions regulate cell proliferation in the sensory epithelia of the inner ear. J Neurosci 2002 22:2607-2616.
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