Neurons undergo dramatic post-mitotic remodeling to replace juvenile with adult features during maturation.  This process heavily relies on temporal gene expression, but how chromatin is regulated to achieve such gene expression dynamics remains minimally defined.  A major challenge is to determine precise mechanisms with cell-type and temporal resolution during development given the extraordinary heterogeneity in the nervous system.  

Our research elucidates how chromatin 3D organization regulates transcriptomic dynamics during neuronal remodeling with unprecedented temporal and cell-type resolution.  We investigate neurons synchronized for their remodeling progression to reveal mechanisms with explicit development relevance. We perform bench and computational analyses with FACS-sorted, ultra-low starting materials to perform bulk analyses for solid quantification.  Meanwhile, we also integrate single-cell and imaging assays to investigate cell-to-cell heterogeneity.  

We will ultimately apply our findings to transcriptionally control neuronal remodeling using organoids derived from patient iPSC and develop molecular therapies to reduce developmental diseases. 

We use fly and mouse models to study neuronal remodeling for fast progress and broad relevance.  

Our fly model provides efficient behavioral readout that screens >500 genes per month to identify essential factors for neuronal remodeling.  Ortholog mutant mice provide opportunities to translate fly findings during vertebrate neuronal development.  

Neuronal remodeling occurs at both cellular and nuclear levels. Another study in our lab investigates nuclear re-organization during retinal rod development and how chromatin architecture facilitates transcription at a global scale. We reported the first global regulation of transcription by the central architectural protein CTCF (Chen et al., 2025, PNAS).