Research
The human body consists of billions of functionally diverse cells that, despite sharing nearly identical genomes, exhibit striking differences in morphology, function, and dynamics. A fundamental question in biology is how diverse cell types organize and interact to form functional communities that give rise to tissue function, and how cells regulate their behaviors in response to environmental stimuli during aging, disease, and other physiological challenges.
To address these fundamental questions, we develop experimental and computational approaches that link molecular features (transcriptome, proteome, etc.) to cell state-specific behaviors (dynamics, cell-cell communication, etc.) at single-cell resolution within intact tissues. By developing state-of-the-art spatial multi-omics tools, we aim to chart cellular states and interactions across space and time, uncovering molecular mechanisms of tissue function and dysfunction to advance cell-based therapies.
How are cell-cell interaction networks rewired in neurodegenerative and diseased brains?
Building on the recently generated spatially resolved whole mouse brain cell atlas, we aim to uncover how cell-cell interaction networks are rewired in disease states. In pathological conditions, disruptions in these networks—particularly at the neuroimmune interface—can drive neurodegeneration, inflammation, and impaired tissue repair. Using the high-resolution spatial transcriptomics technique, MERFISH, we can achieve single-cell, spatially resolved quantification of diverse cell types and states within their native tissue context. This approach allows us to map interaction dynamics, identify disease-associated cellular neighborhoods, and quantify molecular shifts that underlie brain dysfunction. By comparing healthy and diseased brains, we seek to reveal critical interaction changes that may serve as therapeutic targets.
How do cells migrate and establish tumorigenesis niches in primary and metastatic brain tumors?
We utilize MERFISH to map cellular organization and interactions within primary brain tumors and metastatic sites, and track how tumor cells migrate, establish niches, and interact with surrounding cells, including immune and stromal components. To further dissect tumor heterogeneity, we are developing novel in situ mutation detection methods that can be integrated with MERFISH. These approaches will enable us to pinpoint which cell types harbor tumorigenic mutations and uncover how their spatial positioning and interactions contribute to disease progression. Through this, we aim to gain deeper insights into the microenvironmental factors driving tumor evolution and resistance.
How do we capture dynamic cellular processes while maintaining genomic-scale molecular information in single cells?
A major challenge in studying complex biological processes is the lack of methods that can capture dynamic cellular changes while preserving genomic-scale molecular information at single-cell resolution. This limitation hampers our ability to fully understand disease progression, cellular plasticity, and treatment responses in native tissue environments. To overcome this, we are developing an integrated imaging platform that combines vibrational and fluorescence microscopy, leveraging our expertise in genomic-scale single-cell profiling and ultrafast laser spectroscopy. This approach will enable real-time, high-resolution tracking of cellular behaviors while simultaneously preserving rich molecular information, bridging the gap between static molecular snapshots and dynamic cellular processes.
