How does the genome build a brain?
THE LABORATORY OF NEUROGENOMICS
From single-cell genomics and transcriptome imaging to optical electrophysiology and artificial intelligence, we advance genomics and genomic tools to understand across spatial and temporal scales how the genome builds a brain.
THE PROBLEM
The human brain is composed of billions of cells, each belonging to thousands of different types (phenotypes), together forming trillions of connections (circuits) that operate in sync with millisecond precision (dynamics). Yet, at the fundamental level, all cells in the brain are built from the same genetic material (genome). A central focus of our laboratory is to understand how this immense complexity of the brain is achieved by a single genome and how it is influenced by genomic variations.
THE APPROACH
We develop high-throughput genomic and imaging tools to map the brain across extremes of scales—from genes to cells to tissue to organ. By integrating these multi-scale brain maps, we aim to leverage AI predictive models and machine learning methods to uncover the fundamental principles that allow a single genome to generate the complex phenotypes, circuits and dynamics of brain cells, as well as how these genetic circuits malfunction in the cases of disease. Ultimately, we hope to apply this knowledge to engineer cells, accelerating the development of therapeutics.
RESEARCH DIRECTIONS
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Cellular Phenotype
We aim to develop genomic tools to understand, at the single-cell level, how specific genetic pathways—from transcriptional activation to alternative splicing—regulate RNA complexity across various brain cell types, how these processes determine cellular phenotype and vary in changing conditions such as learning and memory.
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Cellular Circuitry
We aim to combine spatial transcriptomics and advanced computational tools such as large language model (LLM) to understand, at the tissue level, how specific intercellular communications—from synaptic connectivity to glia-neuron interactions—are synchronized by intracellular molecular interactions, how these processes malfunction in disease, and ultimately apply this knowledge to engineer cell communication for therapeutic purposes.
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Cellular Dynamics
We aim to combine high-throughput electrophysiology and live-cell imaging with functional genomics to understand, in living cells and organisms, how cellular behaviors and their dynamics—from spiking of single neurons to their communication—are affected by genomic variations across various cell types in health and disease.