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Zheng-Yi Chen, D.Phil.
Associate Professor of Otology and Laryngology, Harvard Medical School

The research interests of my laboratory include 1). Functional genomics of hearing. 2). Inner ear hair cell regeneration. 3). Inner ear stem cell biology.

We take functional genomics approach to systematically study gene expression patterns during mouse inner ear development. This analysis enables us to identify the key pathways underlying different aspects of inner ear development including patterning, cell fate determination, differentiation, function and aging.

Mammalian inner ear lacks the capacity to regenerate hair cells. Using functional genomics approach, we identified the retinoblastoma gene (Rb1) as a gene essential in cell cycle exit and postmitotic maintenance of hair cells, with a potential in hair cell regeneration. We are studying chick and zebrafish models and have identified key pathways involved in hair cell regeneration. We are interested in manipulating those pathways in mouse model to achieve hair cell regeneration and hearing improvement. In addition, we are interesting in using reprogramming of terminally differentiated inner ear cells as a method for hair cell regeneration.

The functional genomics analysis of mouse and chick inner ear has identified a large number of progenitor genes with potential roles in inner ear stem cells. We are interested in evaluating their roles using shRNA and overexpression approaches. This study will help to identify the origin of inner ear stem cells and to facilitate the work using inner ear stem cells for hair cell regeneration.

Selected Publications

1. Sage C, Huang M, Vollrath MA, Brown CM, Hinds PW, Corey DP, Vetter DE and Chen ZY. Essential role of retinoblastoma protein in mammalian hair cell development and hearing . Proc Natl Acad Sci U S A. 2006;103:7345-7350.

2. Sage C, Huang M, Karimi K, Gutierrez G, Vollrath MA, Zhang DS, Garc_a-A_overos J, Hinds PW, Corwin JT, Corey DP, Chen ZY. Proliferation of Functional Hair Cells in Vivo in the Absence of the Retinoblastoma Protein. Science. 2005;307(5712):1114-1118.

3. Rehm HL, Zhang DS, Brown MC, Burgess B, Halpin C, Berger W, Morton CC, Corey DP, Chen ZY. Vascular defects and sensorineural deafness in a mouse model of Norrie disease. J Neurosci. 2002;22(11):4286-92.

4. Liu XZ, Ouyang XM, Xia XJ, Zheng J, Pandya A, Li F, Du LL, Welch KO, Petit C, Smith RJ, Webb BT, Yan D, Arnos KS, Corey D, Dallos P, Nance WE, Chen ZY. Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss. Hum Mol Genet. 2003;12(10):1155-62.

5. Chen ZY, Corey DP. An inner ear gene expression database. J Assoc Res Otolaryngol. 2002;3(2):140-8.