Yuan-Hung Lo
Assistant Professor
The University of Texas Health Science Center at Houston
MD Anderson Cancer Center
Department of Molecular and Cellular Oncology
The Lo Lab is a dynamic and collaborative research team focused on understanding how genetic and epigenetic alterations regulate gastrointestinal (GI) stem cell function, cancer cell plasticity, and clonal evolution during tumorigenesis. We develop and apply advanced genetic tools and physiologically relevant 3D organoid models derived from primary human tissues to investigate the molecular and cellular mechanisms that drive cancer initiation, progression, and therapeutic response. Our long-term goal is to uncover actionable biology that leads to improved prevention and treatment strategies for GI cancers. Our research integrates the following key areas: o Modeling Cancer in Primary 3D Organoids: We use CRISPR/Cas9 genome editing to sequentially introduce oncogenic mutations (e.g., TP53, ARID1A, KMT2D) into normal human gastric organoids, enabling us to functionally model early events in human cancer. These models recapitulate key stages of pre-malignant transformation and allow longitudinal tracking of clonal evolution and epigenetic reprogramming under defined environmental conditions. o Dissecting Cell Plasticity and Clonal Evolution: We study how (epi)genetic regulators and environmental insults interact to promote the emergence of aberrant hybrid cell states and malignant clones. Our work has uncovered novel hybrid cell populations with enhanced plasticity and tumorigenic potential, suggesting they may serve as early cancer-initiating populations. Using single-cell multiomic profiling and innovative long-read sequencing, we aim to define the molecular circuits that govern these dynamic lineage transitions. o Functional Genomics of Tumor-Microenvironment Interactions: We are developing human organoid-based co-culture platforms to explore how tumor cells interact with the stromal and immune compartments of the microenvironment. These models provide a valuable system for studying tumor-immune dynamics, therapeutic resistance, and immune evasion in a human-relevant context. Collectively, our research bridges fundamental cancer biology with translational relevance by leveraging human organoid models to understand how cancer cell identity is shaped and reprogrammed during transformation. We are particularly interested in uncovering shared vulnerabilities and new intervention strategies targeting early-stage disease.
Education & Training
Ph.D. - Baylor College of Medicine - 2017