Image-based Spatial Genomics in Health and Disease*

The three-dimensional (3D) organization of the genome affects many genomic functions. Changes in genome architectures have been associated with normal development, aging, and a wide range of diseases. Despite its critical importance, understanding the spatial organization of genome in single cells, the variation of the organization in diverse cell types in complex mammalian tissue, and the regulatory mechanisms and functions of the organization in different biomedical processes remains a major challenge. To address these questions, we developed image-based 3D genomics and spatial multi-omics techniques termed chromatin tracing and MINA to map 3D genome and multi-ome in single cells and complex mammalian tissues. We are applying these developments to depict multiscale genomic architectures associated with gene expression and other genomic functions in different types of cells and tissues undergoing different biological processes in cancer, aging, and immunology. We are also systematically identifying novel regulators of 3D genome by developing high-content image-based CRISPR screens. These novel regulators may serve as a new class of therapeutic targets to halt or even reverse deleterious 3D genome changes in diseases. In sum, the talk will focus on our efforts on: 1) characterizing the 3D genome with new technology developments, 2) understanding 3D genomic functions in the native tissue context in health and disease, and 3) building the 3D genomic “regulatome” to manipulate the 3D genome.