Harold Hodgkinson Professor
Departments of Biomedical Engineering and of Pathology
Yale University
Title: Decoding Human Molecular Biology by Novel Spatial Multi-Omics
Abstract: From Hippocrates’ observations of illness to anatomical investigation and cellular pathology, understanding human biology and disease has depended on examining the human body at progressively finer scales. Molecular biology introduced a complementary approach: explaining how genes, proteins, and regulatory processes govern cellular function. Yet, a foundational divide persists between examining tissue architecture and understanding its molecular basis. Spatial omics bridges these perspectives, revealing how molecular programs unfold cell by cell within human tissues. Our laboratory pioneered spatial multi-omics through the first co-mapping of the whole transcriptome and proteins using Deterministic Barcoding in Tissue (DBiT) (Liu et al., Cell, 2020). We subsequently demonstrated spatial epigenome sequencing (Deng et al., Nature, 2022; Science, 2022), followed by joint epigenome–transcriptome profiling (Zhang et al., Nature, 2023), connecting chromatin regulation to gene expression in tissues. Patho-DBiT extends these investigations to clinical archival formalin-fixed, paraffin-embedded specimens (Bai et al., Cell, 2024). Beyond protein-coding transcripts, it reveals the noncoding “dark transcriptome,” splicing isoforms, and expressed sequence variants, enabling investigation of RNA regulation, malignant subclones, and their cellular neighborhoods directly in human tissues. These advances transform clinical specimens into resources for studying molecular biology in its native context. Coupled with artificial intelligence (AI), spatial multi-omics provides a foundation for predictive models integrating molecular regulation, cellular interactions, and tissue organization. Such models could identify therapeutic targets, predict responses to perturbations, and guide precision health. In this talk, I will discuss how these perspectives illuminate human biology, aging, and disease, connecting molecular discoveries in human tissues to diagnostic and therapeutic opportunities.
Host: Jellert Gaublomme
