PiN Faculty Member - Zheng-Yi Chen, DPhil

Zheng-Yi Chen, D Phil

Associate Professor of Otolaryngology

Massachusetts Eye and Ear Infirmary
Eaton-Peabody Laboratory
243 Charles Street
Boston, MA 2114
Tel: 617-543-3673
Fax: 617-720-4408

Hearing loss is the most common sensory deficits affeting humans without medical treatment.

The research of my laboratory can be divided into following parts: a) understanding the causes of hearing loss; b) development of genome editing as treatment for hearing loss; c) development of gene therapy to treat hearing loss; d) inner ear regeneration.

We use animal models and RNAseq to uncover the pathways involved in different forms of hearing loss due to noise exposure, drug toxicity and aging. The genes and pathways identified serve as potential targets for intervention to treat hearing loss.

We have successfully developed in vivo genome editing to treat dominant genetic hearing loss by RNP (ribonucleoproteins) delivery in mouse models with substantially reduces off-target effect. We have created pig models for human genetic hearing loss and have created iPS cell lines from patients with genetic hearing loss. We are building a platform to carry out genome editing in pig models to restore hearing and in human patient samples before moving our work to clinic. We are expanding genome editing toolbox including novel delivery vehicles and endonucleases to treat diverse forms of genetic hearing loss.

We are developing AAV-based therapy to treat noise-induced and age-related hearing loss. We have shown that both types of hearing loss can be protected by overexpression of ISL1 gene in inner ear hair cells, the sensory cells that detect sounds. We will uncover the pathways elicited ISL1 overexpression and develop a treatment paradigm for both types of hearing loss. We are developing AAV approach to treat human genetic hearing loss.

Hearing loss and balance disorders are permanent because human inner ear does not have the capacity to regenerate. We have shown by reprogramming that adult mammalian inner ear cells can be induced to enter cell cycle. Further reprogrammed supporting cells respond to hair cell induction signals and transdifferentiate to hair cell efficiently. We have developed an in vitro explant culture system for adult mouse cochlea to test regeneration efficiently. We are using reprogramming regenerate hair cells and other inner ear cell types to treat hearing loss as the result of inner ear degeneration.

Last Update: 9/16/2020


For a complete listing of publications click here.



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