Longzhi Tan

How do cells in our nervous system develop highly specialized functions after birth, and how do they degenerate as we age? An emerging molecular mechanism is 3D genome architecture—the folding of 6 billion base pairs of DNA (~2 meters) into a tiny cell nucleus (~10 microns). This folding can strategically position genes and their regulatory elements in 3D to orchestrate dynamic gene expression, and has been implicated in many developmental and degenerative diseases (e.g., autism, schizophrenia, Alzheimer’s). However, traditional technologies and algorithms struggle to capture the full complexity of genome architecture of a single cell, and the enormous heterogeneity between cells. In addition, most studies interrogate genome architecture in vitro, taking cells out of their physiological context. The Tan Laboratory of 3D Genomics at Stanford Neurobiology studies the single-cell 3D genome architectural basis of neurodevelopment and aging by developing the next generation of in vivo multi-omic assays and algorithms, and applying them to the human and mouse cerebellum and beyond (e.g., cancer, immunology).