Research Area Affiliations
Dr. Huang aims to identify genes critical for regeneration of mammalian hair cells, the inner ear sensory cells that detect sound and sense balance. Most of the hearing loss and vestibular dysfunction in human is caused by irreversible loss of hair cells, which cannot be spontaneously regenerated. Using microarrays, Dr. Huang systematically studied expression profiles of genes in the mouse genome during inner ear development and identified genes potentially important in inner ear development. These genes include potential deafness genes and genes implicated in regeneration. He has found one such gene, the retinoblastoma gene (Rb1), which is required in blocking hair cell regeneration. By conditionally removing Rb1 in the inner ear, Dr. Huang showed that differentiated hair cells undergo proliferation to regenerate new and functional hair cells in young mice. He further analyzed expression profiles of Rb1 knockout mice and controls, and showed that the E2F pathway was the core pathway altered in Rb1 inner ear. He has further identified other pathways implicated in the Rb1 pathway, which can be further manipulated for hair cell regeneration.
Another line of research that Dr. Huang studies is age-related and noise induced hearing loss (ARHL & NIHL). He has recently shown that by overexpression of an inner ear progenitor gene, Isl1, both forms of deafness can be significantly reduced. This is achieved primarily by promoting hair cell survival in both conditions. This conclusion is significant as it supports that a similar mechanism underlying ARHL and NIHL in the model, and provides a route to achieve hearing protection by the function of one gene. His laboratory is working on identifying Isl1 target genes to understand the protection mechanism, as well as on screening for compounds to activate Isl1 for the hearing protection.
Hair cell overexpression of Islet1 reduces age-related and noise-induced hearing loss. Huang, M., Kantardzhieva, A., Scheffer, D., Liberman, M. C., Chen, Z. Y. (2013) J. Neurosci. 33(38), 15086-15094.
Overlapping and distinct pRb pathways in the mammalian auditory and vestibular organs. Huang, M., Sage, C., Tang, Y., Lee, S. G., Petrillo, M., Hinds, P. W., Chen, Z. Y. (2011) Cell Cycle 10(2), 337-351.
Diverse expression patterns of LIM-homeodomain transcription factors (LIM-HDs) in mammalian inner ear development. Huang, M., Sage, C., Li, H., Xiang M., Heller, S., Chen, Z. Y. (2008) Dev. Dyn. 237(11), 3305-3312.
Essential role of retinoblastoma protein in mammalian hair cell development and hearing. Sage, C., Huang, M., Vollrath, M. A., Brown, M. C., Hinds, P. W., Corey, D. P., Vetter, D. E., Chen, Z. Y. (2006) Proc. Natl. Acad. Sci. USA 103(19), 7345-7350.
Proliferation of functional hair cells in vivo in the absence of the retinoblastoma protein. Sage, C., Huang, M., Karimi, K., Gutierrez, G., Vollrath, M. A., Zhang, D. S., Garcia-Anoveros, J., Hinds, P. W., Corwin, J. T., Corey, D. P., Chen, Z. Y. (2005) Science 307(5712), 1114-1118.
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