Precise gene regulation is essential for maintaining cellular homeostasis and developmental processes. Because gene expression is regulated in a real-time manner, it needs to be examined with spatio-temporal approach. Interaction between physical dynamics of genomic information harboring chromatin and the nuclear bodies are studied through fluorescence imaging in living cells. By fluorescence labeling of chromatin and capturing the proteins in nuclear bodies with super-resolution imaging, we investigated how their interaction influences gene expression.

We investigated the relationship between the Integrator complex and transcriptional condensates. Transcriptional condensates are formed at activated gene loci. INTS11 depletion results in production of longer, more abundant eRNAs. Under an “RNA-mediated condensate regulation” model, these aberrant eRNAs could modulate Mediator condensation. Our imaging data revealed direct co-localization among Integrator, Pol II condensates, and Mediator condensates. We are currently investigating how transcriptional condensates change depending on Integrator endonuclease activity. 

Biomolecular condensates organize the transcriptional machinery through liquid-liquid phase separation (LLPS). While transcription machineries like MED1 and Pol II compartmentalize to facilitate expression, the mechanisms preventing their aberrant condensation remain unclear. This project identifies CDK8 as a "gatekeeper" that restrains MED1's multivalent interactions. To investigate this, we employ a combination of super-resolution imaging and high-throughput sequencing to monitor the dynamics of these condensates and their impact on the genomic landscape.

Transcription factors (TFs) regulate gene activation and repression by binding to specific genomic loci and recruiting co-regulators. Through these mechanisms, TFs orchestrate transcriptional programs and play pivotal roles in cellular differentiation and cell fate determination. During differentiation, lineage-specific TFs activate cell fate–determining genes, thereby directing cells toward specific lineages. In this study, we investigate transcriptional condensates as dynamic regulatory hubs that coordinate LLPS-mediated assembly of transcription factors, thereby fine-tuning gene expression dynamics during development and cell fate transitions. 

We investigate how the coordination between mitochondria and stress granules (SGs) orchestrates cellular adaptation to environmental stress. By examining the role of mitochondrial dynamics in SG fusion and maturation, we have uncovered a survival mechanism for maintaining cellular integrity under adverse conditions.  Currently, we are focused on elucidating the specific molecular mechanisms underlying SG–mitochondria contact sites.

We explore the active role of vimentin in cellular protein quality control (PQC). By integrating advanced spatiotemporal imaging, we investigate the organizational principles of misfolded proteins. Our goal is to uncover conserved dynamics across neurodegenerative models, providing a foundation for novel therapeutic strategies to restore proteostasis. 

We develop engineered tissue models for high-resolution imaging of cellular and subcellular responses to drug exposure. By integrating advanced microscopy with controlled tissue culture systems, our platform enables systematic acquisition of single-cell images capturing drug-induced morphological changes. We aim to organize these datasets into AI-ready libraries of drug-induced cellular responses, enabling computational analysis and predictive modeling of drug effects. This platform also opens opportunities for collaborative studies in drug discovery and preclinical evaluation.

Leveraging an advanced fluidics system and high-resolution microscopy, our lab has established a robust MERFISH pipeline for spatial transcriptomics. This powerful technology can reveal detailed tissue architecture, cellular activity, and molecular pathology at single-cell resolution. The brain, with its immense complexity and spatial heterogeneity, is an ideal candidate for such analysis. Currently, we are mapping the activity landscape of the mouse hypothalamus in the context of social interaction. However, the applicability of MERFISH extends to diverse tissues across species. We welcome new collaborations and innovative ideas to explore the complex molecular architectures of tissues.

The spatiotemporal changes in chromatin structure during DNA double-strand breaks (DSBs) and the subsequent repair processes, as well as their functional implications, are not yet fully understood. Our research aims to elucidate the 3D chromatin architecture under DSB conditions, utilizing Optical Reconstruction of Chromatin Architecture (ORCA) for super-resolution chromatin structure imaging.