Curiosity gets fulfilled here


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. 

​     Painting credit goes to an evolution enthusiast Silu Wang

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.  

We published temporal regulation of chromatin 3D organization that facilitates stage-specific gene expression in flies prior to other systems (Chen et al., 2021, Nat. Commun.).  We are investigating how this temporal regulation is achieved in mice by disease-risk factors that play central roles in chromatin 3D organization.

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). 

We perform comparative analyses to identify conserved, chromatin-related mechanisms underlying neuronal remodeling in flies and mice.  These analyses investigate gene expression (RNA-seq), chromatin accessibility (ATAC-seq), chromatin association of proteins (CUT&Tag) and global chromatin 3D structure (Micro-C) etc, all of which are performed with sorted neurons.

Left is an example of the finished fly RNA-seq analyses and ongoing mouse RNA-seq analyses.  Thousands of genes display remodeling-biased expression in fly neurons that include most top autism-risk genes.  We are excited to determine how these risk factors regulate chromatin during normal and pathological development.