The Zhao Laboratory develops sequencing-based technologies to map cellular communication networks across diverse biological systems. We combine chemical biology, genomics, and neuroscience to study how cells establish, maintain, and adapt their connections in health and disease.

Many biological processes—from neural circuit function to cancer progression to developmental transitions—depend on organized cell-cell communication. By converting connectivity mapping from a microscopy problem into a sequencing problem, we can analyze these networks at scales and resolutions that complement existing approaches.

Our research focuses on three interconnected areas:

1. Connectivity Mapping Technologies

We developed Connectome-seq, a sequencing-based method for mapping cellular connectivity at single-connection resolution. Connectome-seq enables simultaneous analysis of thousands of interactions by leveraging synaptic structures, and is applicable to neurons, neuron-glia interactions, and neuron-cancer connections. Building on this foundation, we are developing Communicatome-seq to extend beyond synaptic structures and map all types of cell-cell contacts. This approach is applicable to biological systems where contact-dependent communication governs cellular behavior, enabling connectivity analysis at whole-tissue and whole-organism scales.

2. Integrated Multi-Omics Molecular Profiling

We combine proximity labeling technologies, epigenetic/epitranscriptomic modifications analysis, and sequencing approaches to profile the molecular factors that enable cells to establish, maintain, and adjust their communication interfaces. These platforms reveal molecular signatures that define specific cellular interactions and communication states. By characterizing both structural connectivity and underlying molecular programs, we can understand how cells regulate their connections dynamically in response to developmental cues, physiological needs, or pathological conditions.

3. Analysis of Diverse Biological Systems

We apply our connectivity mapping and multi-omics profiling platforms to study multiple biological systems. These include neural circuits (stable and activity-dependent connections), neuron-glia communications, and cancer-neuron synapses. By using both sets of tools across these contexts, we identify principles governing how cells coordinate their behavior in multicellular organisms, independent of specific organ systems or disease states. This comparative approach helps elucidate fundamental aspects of cellular organization in both normal physiology and disease.

Our interdisciplinary approach trains scientists at the intersection of technology development and biology, creating tools that advance understanding of cellular organization in physiological and disease contexts.