ZHENG-YI CHEN, D. PHIL.

Massachusetts Eye and Ear Infirmary
Main Campus
243 Charles Street
Boston, MA 02114

RESEARCH INTERESTS

Dr. Chen’s research interests include functional genomics of hearing, inner ear hair cell regeneration, mechanisms and treatment for age-related and noise-induced hearing loss (ARHL and NIHL) and gene therapy for hereditary deafness.

Dr. Chen’s long-term research goals are to identify genes and functional pathways that govern the development, function and disease state of the inner ear, and to develop therapies for different types of deafness in humans.

One of the most common causes of hearing loss is the loss of hair cells, the inner ear sensory cells that detect sound and sense balance. Regeneration of hair cells in the adult mammalian inner ear has been the most prominent obstacle to overcome. Dr. Chen’s laboratory takes a functional genomics approach to systematically study gene expression patterns during mouse inner ear development. They have identified the retinoblastoma gene (Rb1) as the key gene controlling cell exit in hair cells and supporting cells, with an implication in hair cell regeneration in young mammalian inner ears.

Using chicken and zebrafish models, they identified new key genes in hair cell regeneration in lower vertebrates. They demonstrated that the function of the genes are sufficient to induce proliferation of hair cells and supporting cells in adult and aged mammalian inner ears, resulting in regeneration of functional hair cells. His laboratory is working on elucidating the mechanisms underlying proliferation and regeneration, and they are developing strategies to regenerate adult hair cells for hearing recovery in animal models and to regenerate human hair cells.

DR. CHEN’S LABORATORY

Dr. Chen’s laboratory has a long-standing interest in genetic hearing loss. The laboratory has been involved in cloning and characterizing numerous deafness genes. Though more than one hundred genetic deafness genes have been identified, still no therapy is currently available. The next frontier in genetic hearing loss is the development of treatment. The laboratory has recently shown that proteins can be directly delivered into the mammalian inner ear in vivo with functional consequences.

Dr. Chen’s laboratory has used protein delivery to demonstrate genome editing in the inner ear hair cells by CRISPR/Cas9 technology. They are now working on combining protein delivery and genome editing as a potential new treatment for genetic hearing loss. This combinatory approach should open the doors to the efficient study of virtually all genes in the inner ear.

Using a transgenic approach, Dr. Chen’s laboratory uncovered that hair cell overexpression of Isl1, an inner ear progenitor gene, resulted in protection from age-related and noise-induced hearing loss (ARHL & NIHL) in mice. Hair cells expressing Isl1 are resistant to cell death (apoptosis). This study underscores a common mechanism underlying ARHL and NIHL. Using mass sequencing, the laboratory is investigating the Isl1 targets and screening for compounds that can be used for protection against ARHL and NIHL.

EDUCATION AND TRAINING

  • Postgraduate Training & Research Fellowship: Neurology, Massachusetts General Hospital

  • 1992 – D.Phil. Human Genetics, Oxford University

  • 1984 – B.Sc. Genetics, Sichuan University

COMMITTEES / SOCIETIES / MEMBERSHIPS

  • The American Society of Human Genetics

  • The Association for Research in Otolaryngology

  • Society for Neuroscience

  • American Society of Gene and Cell Therapy

HONORS AND AWARDS

  • 2004: Pfizer/AFAR Innovations in Aging Research Program, American Federation for Aging Research

  • 2005: Research Leader, The 2005 Scientific American 50, Scientific American

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