About

Zheng-Yi Chen is an Associate Professor of Otolaryngology, Head and Neck Surgery at Massachusetts Eye and Ear Infirmary. His laboratory focuses on understanding the causes of hearing loss, developing genome editing and gene therapy treatments, and exploring inner ear regeneration. His research employs animal models and RNA sequencing to uncover pathways involved in hearing loss due to noise exposure, drug toxicity, and aging. He has successfully developed in vivo genome editing techniques to treat dominant genetic hearing loss using RNP delivery in mouse models, and has created pig models and iPS cell lines from patients with genetic hearing loss. His team is building platforms for genome editing in pig models and human samples, expanding the toolbox with novel delivery vehicles and endonucleases, and developing AAV-based therapies to treat noise-induced and age-related hearing loss. Additionally, he investigates reprogramming adult mammalian inner ear cells to induce regeneration of hair cells and other inner ear cell types, aiming to treat hearing loss caused by inner ear degeneration. His work includes developing in vitro explant culture systems and exploring pathways for hair cell regeneration, with the goal of restoring hearing and balance functions.

Research topics

• Computer Science
• Biology
• Genetics
• Computational biology
• Pediatrics
• Internal medicine
• Data science
• Medicine
• Audiology

Selected publications

• Multicentre gene therapy for OTOF-related deafness followed up to 2.5 years

  Nature · 2026-04-22 · 1 citations

  article
  PublisherDOI

• Outcomes of genetic testing for Usher syndrome in a diverse population cohort from South Florida

  Human Genomics · 2025-06-18 · 1 citations

  articleOpen access

  BACKGROUND: Usher syndrome (USH) is the leading genetic cause of congenital deaf blindness worldwide. USH is an autosomal recessive disorder clinically characterized by partial or complete congenital sensorineural hearing loss followed by progressive vision loss due to retinitis pigmentosa. There are three main subtypes (USH1, USH2, USH3) with different genetic causes categorized by age of symptom onset and severity. Understanding the genetic epidemiology of USH can help identify novel mutations and facilitate definitive diagnosis and treatment. This retrospective study characterizes the mutation spectrum of USH in an ethnically diverse South Florida population. RESULTS: Of the 148 patients assessed for this study, 67 were male and 81 were female. In this population, one identified as American Indian or Alaska Native, 6 identified as Asian (A), eight identified as Black or African American (AA), eight identified as More than One Race, 26 were identified as Unknown or Not Reported, and 99 were identified as white. In addition, 42 identified as Hispanic or Latino, 87 identified as Non-Hispanic or Latino, and 19 were identified as Unknown or Not Reported; all individuals identifying as Hispanic or Latino were either White or Unknown. One American Indian or Alaska Native patient, two Asian patients, two Black or African American Patients, and 15 white patients had inconclusive molecular testing results. In our population, White Non-Hispanics were more likely to receive a conclusive molecular diagnosis for their hearing loss. CONCLUSIONS: This is the first genetic characterization of an ethnically diverse South Florida population with USH, which can help direct patient diagnosis and medical care. As clinical trials for treatment increases, molecular testing in all individuals is imperative.

  PublisherOA PDFDOI

• Mutant GNAS Drives a Pyloric Metaplasia with Tumor Suppressive Glycans in Intraductal Papillary Mucinous Neoplasia

  SSRN Electronic Journal · 2025-01-01 · 1 citations

  preprintOpen access
  PublisherDOI

• Single-dose genome editing therapy rescues auditory and vestibular functions in adult mice with DFNA41 deafness

  Journal of Clinical Investigation · 2025-08-14 · 1 citations

  articleOpen accessSenior author

  Genome editing has the potential to treat genetic hearing loss. However, current editing therapies for genetic hearing loss have shown efficacy only in hearing rescue. In this study, we evaluated a rescue strategy using adeno-associated virus (AAV) type 2-mediated delivery of Staphylococcus aureus Cas9-sgRNA in the mature inner ear of the P2rx2V61L/+ mouse model of autosomal dominant deafness-41 (DFNA41), a dominant, delayed-onset, and progressive hearing loss in humans. We demonstrate that local injection in adult mice results in efficient and specific editing that abolishes the mutation without notable off-target effects or AAV genome integration. Editing effectively restores long-term auditory and vestibular function. Editing further protects P2rx2V61L/+ mice from hypersensitivity to noise-induced hearing loss, a phenotype also observed in patients with DFNA41. Intervention in mice at a juvenile stage broadens the frequency range rescued, highlighting the importance of early intervention. An effective and specific gRNA for the human P2RX2 V60L mutation has been identified. Our study establishes the feasibility of editing to treat DFNA41 caused by P2RX2 V60L mutation in humans and opens an avenue for using editing to rescue hearing and vestibular function while mitigating noise-induced hearing loss.

  PublisherDOI

• Activation and inhibition of Notch signaling facilitate proliferative regeneration of sensory cells in adult mice

  Eye & ENT Research · 2025-04-23

  articleOpen access

  Abstract Due to the limited regenerative capacity in adult mammals, the loss of vestibular hair cells (HCs) leads to balance disorders. In this study, we chronologically reprogrammed adult vestibular supporting cells (SCs) via bimodal regulation of Notch signaling, mimicking dynamic changes in Notch signaling during inner ear development. We found that activating Notch signaling stimulated SC proliferation in damaged adult utricles, priming these cells with the potential to regenerate sensory HCs. Subsequent inhibition of Notch signaling removed lateral inhibition barriers, promoting the transition from proliferating SCs to HCs. Our findings underscore the crucial role of Notch signaling in promoting vestibular HC regeneration.

  PublisherOA PDFDOI

• Clinical gene therapy restores hearing: a paradigm shift

  Trends in Molecular Medicine · 2025-09-03 · 2 citations

  review
  PublisherDOI

• Author response for "Generation and Auditory Phenotypic Characterization of Prps1 p.<scp>Ala87Thr</scp> Mouse Knock‐In Model for Human <scp>DFNX1</scp> Deafness"

  2025-05-12

  peer-review
  PublisherDOI

• Optimization effect of video data extraction and search based on Faster-RCNN hybrid model on intelligent information systems

  Nonlinear Engineering · 2025-01-01 · 1 citations

  articleOpen accessSenior author

  Abstract The swift surge of video content depicts enormous challenges for intelligent information systems in extracting and searching video data. This article explores improvements achieved by introducing a Faster-RCNN hybrid model into video data extraction and search processes. We propose a novel methodology combining Faster-RCNN with adaptive feature fusion and temporal coherence modeling to enhance object detection and tracking within video streams substantially. Using a large multi-megavideo dataset called VideoDiv-10K, which is made up of 10,000 videos from categories and others made available through public datasets like ImageNet VID and MOT16, this proposed model exhibited magnificent improvements. This model, when hybrid used with 500 h of content diversity, produced an average mean average precision of 0.891 and had an improved amount by 18.7% more than traditional Faster-RCNN. The model reduced its time for computation by 32.4% and had a massive leap in the accuracy in the search by 41.2%. Key to this performance were the temporal coherence module, which does a good job in capturing dependencies within sequential frames, and the adaptive feature fusion mechanism that dynamically integrates spatial and temporal features. Those were used to attain average F 1-score in object detection of 0.937 and 0.912 object tracking on some video resolutions and frame rates. The results of the experiment clearly prove the ability of our hybrid model to process large video data, with significant gains in both accuracy and speed. We then provide better performance within applications such as surveillance, autonomous driving, and content-based video retrieval. Our model maintains a high level of scalability and does not degrade for huge datasets.

  PublisherOA PDFDOI

• Generation and Auditory Phenotypic Characterization of Prps1 p. <scp>Ala87Thr</scp> Mouse Knock‐In Model for Human <scp>DFNX1</scp> Deafness

  Clinical Genetics · 2025-06-10

  articleOpen access

  Variants in the phosphoribosylpyrophosphate synthetase (PRPS1) gene have been shown to cause X-linked nonsyndromic hearing loss (HL) (DFNX1) in humans. A c.259G>A transition in PRPS1, which leads to p.Ala87Thr, has been demonstrated to cause HL. The aim of this study was to generate a transgenic knock-in (KI) mouse with the Prps1 missense variant p.Ala87Thr and to study its impact on the auditory phenotype. Compared to wild-type (WT) control, transgenic Prps1 KI mice started to exhibit HL at 32 kHz at 4-12 weeks of age, with HL extending to 8 and 16 kHz by 48 weeks of age. A significant decrease in the number of hair cells and spiral ganglion neuron (SGN) counts was observed at 48 weeks of age in transgenic KI mice. These traits may be associated with the Bak-dependent mitochondrial apoptosis program, which is triggered by oxidative stress and has been identified as a key mechanism of age-related HL in C57BL/6J mice. Enzymatic assay showed a significant reduction in Prps1 enzymatic activity in KI compared to WT animals. The Prps1 p.Ala87Thr KI mouse model will serve as a valuable tool for developing therapeutic strategies to mitigate HL associated with PRPS1 variants.

  PublisherOA PDFDOI

• Author response for "Generation and Auditory Phenotypic Characterization of Prps1 p.&lt;scp&gt;Ala87Thr&lt;/scp&gt; Mouse Knock‐In Model for Human &lt;scp&gt;DFNX1&lt;/scp&gt; Deafness"

  2025-04-03

  peer-review
  PublisherDOI

Recent grants

• NIH Grant R01DC006908

  NIH · $2.7M · 2017

• Efficient in Vivo RNP-based Gene Editing in the Sensory Organ Inner Ear Using Bioreducible Lipid Nanoparticles

  NIH · $1.6M · 2018–2023

• Efficient in Vivo RNP-based Gene Editing in the Sensory Organ Inner Ear Using Bioreducible Lipid Nanoparticles

  NIH · $831k · 2018–2023

• Development of Genome Editing as Treatment for Genetic Hearing Loss

  NIH · $3.0M · 2019–2024

• NIH Grant R01DC004546

  NIH · $1.7M · 2007

Frequent coauthors

• Mingqian Huang

  Harvard University

  131 shared

• Yilai Shu

  Institutes of Science and Development

  100 shared

• David P. Corey

  Boston University

  99 shared

• Cyrille Sage

  Howard Hughes Medical Institute

  62 shared

• Philip W. Hinds

  Tufts University

  55 shared

• Melissa A. Vollrath

  McGill University

  53 shared

• Duan-Sun Zhang

  Howard Hughes Medical Institute

  52 shared

• Kambiz Karimi

  Massachusetts General Hospital

  49 shared

Education

• Ph.D., Neuroscience

  Harvard University

  2013

• B.S., Biology

  National Taiwan University

  2007