Zheng-Yi Chen, D.Phil

Assistant Professor of Neurology

Massachusetts Eye & Ear Infirmary

Eaton-Peabody Laboratory
Department of Otolaryngology
243 Charles Street
Boston, MA 02114
Telephone: 617-573-3673
Fax:617- 720-4408
Email: zhengyi@helix.mgh.harvard.edu
Predocs: 0 Postdocs: 3 Completed PhD's:0

The research of my laboratory can be divided into three main parts: a)functional genomics of hearing; b) inner ear cell regeneration and c) molecular basis of genetic deafness. Our long-term goals are to identify genes and functional pathways that govern the development, function and disease state of the inner ear.

To identify genes and pathways important in inner ear development and function, we have used microarray to study the gene expression profiles of developing mouse utricle, one of the vestibular organs. The study has identified most of genes and pathways in individual cell types that are likely to be involved in stem cell and progenitor cell specification, cell fate determination and differentiation and inner ear function. We are conducting a large-scale in situ hybridization for fine localization and using zebrafish models to test functions of some genes. Many genes showed enriched expression profiles in the inner ear. They are being screened for possible mutations in genetic deafness.

Hearing loss and balance disorders are permanent because mammalian hair cells, the sensory cells of the inner ear, become postmitotic during early embryonic development and they lack the capacity of self-renewal. From microarray studies we have identified retinoblastoma gene (Rb) that plays an essential role in cell cycle exit and postmitotic state of hair cells. Using various conditional Rb knockout mouse models, we have shown that differentiated and functional hair cells can be regenerated through cell cycle reentry. We are expanding the work, using RNAi approach, to transiently block pRb function in adult mouse inner ear.Our goal is to manipulate pRb pathway in mature inner ear, to regenerate functional hair cells and achieve functional recovery from deafness and balance disorders.

Selected References:

• Rehm H, Zhang DS, Brown MC, Burgess B, Halpin C, Berger W, Morton CC, Corey DP, Chen ZY. (2002) Vascular defects and sensorineural deafness in a mouse model of Norrie Disease. J Neurosci 22, 4286-4292.
• Lu XZ, Zheng J, Ouyan XM, Xia XJ, Li F, Du LL, Corey DP, Pandya A, Petit C, Smith RJH, Dallos P, Balkany T, Nancy WE, Chen ZY. (2003) Prestin, a cochlear motor hearing protein, is defective in non-syndromic hearing loss. Hum Mol Genet 12; 1155-1162.
• Sage C, Huang MQ, Karimi K, Vollrath MA, Zhang DS, Gutierrez G, Hinds P, Corwin JT, Corey DP and Chen ZY. (2005) Proliferation of functional hair cells in vivo in the absence of retinoblastoma protein. Science 307, 997-1152