Events / Biomedical Data Science Seminar Series: “Tracking the origins, progression, and clonal evolution of colorectal precancer to cancer” (Ken Lau)

Biomedical Data Science Seminar Series: “Tracking the origins, progression, and clonal evolution of colorectal precancer to cancer” (Ken Lau)

November 20, 2024
4:00 pm - 5:00 pm

John Morgan Building, Reunion Auditorium

Abstract: Recent genome-scale profiling approaches have transformed our understanding of tissue biology, particularly in human specimens. We discuss biological insights into colorectal precancer initiation and progression gleaned from multi-omic profiling of human colorectal tumors. Single-cell transcriptomic and multiplex imaging analyses of the two most common human colorectal precancers, conventional adenomas and serrated polyps revealed that adenomas originate from WNT-driven stem cell expansion, while serrated polyps develop through gastric metaplasia. The stem and metaplasia dichotomy, as well as their accompanying unique immune microenvironments, persist into their cancer counterparts. Spatial profiling data generated from colorectal tumor specimens unveiled personalized evolutionary dynamics and corresponding microenvironment alterations. Notably, an Immune Exclusion signature associated with progression of tumor regions with chromosomal instability (CIN+), influencing cytotoxic cell infiltration and providing prognostic value. Furthermore, clonal analysis of a substantial number of human polyps demonstrated the occurrence of polyancestral initiation in 15-30% of colonic precancers, revealing their origins from multiple normal founders. These results enhance our understanding of tumor initiation and progression, enabling precision surveillance and potential targeted interventions.

 

Bio: Dr. Ken Lau was born in Hong Kong and grew up in Toronto, Canada, where received his Bachelors of Science and his Ph.D. in Proteomics and Bioinformatics (2008) from the University of Toronto. After a joint postdoctoral fellowship at MIT and Massachusetts General Hospital, he was recruited to the Vanderbilt Epithelial Biology Center and the Department of Cell and Developmental Biology as a tenure-track in 2013, and was promoted to Associate Professor with tenure in 2019, and Full Professor in 2023. Dr. Lau’s laboratory applies data-driven systems biology approaches to understand cellular specification and function in the gut. His lab develops and utilizes single-cell and spatial technologies and data science algorithms to study cellular networks. His lab is broadly interested in the interactions between epithelium and the microbiome, cell states in stem cell biology and development, and the origins of cancer.