Epithelial Stem Cells and Cancer
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Nick Barker Lab
Research Projects
Our research projects mainly focus on epithelial stem cell biology and its application to disease states such as cancer. Epithelial stem cells that we are currently investigating are those found in the stomach, intestines and esophagus.
Gastric cancer is one of the leading causes of cancer-linked deaths, particularly in Asia. Our lab has generated complex gastric stem cell-driven cancer mouse and organoid models capable of recapitulating physiologically-relevant features of human gastric cancer initiation and progression, facilitating the study of stem cell contributions to cancer and the development of new targets and approaches for disease amelioration. We have also identified novel markers of gastric cancer stem cells that allow us to efficiently isolate, target, and characterize these cells and their underlying mechanistic functions.
Intestinal stem cells
Colorectal cancer (CRC) is the third most diagnosed and second most lethal cancer worldwide. Current CRC mouse models lack either colon tissue-specificity, limiting progression towards more advanced disease, or preclude evaluation of resident stem cells as cancer origins. We have identified specific stem cell markers for different regions of the colon and generated Cre driver mouse models. We are now using these models to study stem cell contributions to colon cancer and for use in developing accurate models of advanced human colon cancer.
Esophageal stem cells
The esophageal epithelium lacks a defined stem cell niche, and it remains an open question in the field whether the basal layer cells are homogenous or form a heterogeneous pool. Our lab utilises advanced mouse models and transcriptional/spatial profiling techniques to identify esophageal stem/progenitor cells and investigate their contributions to esophageal organogenesis. Through our research, we have discovered discrete Lgr5+ populations within different esophageal cell clusters that are active during embryogenesis with a remarkable ability to generate long-lived clones and persist in the tissues long-term after birth, shedding light on the crucial role played by Lgr5+ stem/progenitor cells during organogenesis, and laying a solid foundation for future investigations into esophageal diseases.
Arf/p53 in Tissue Regeneration and Carcinogenesis
Point missense mutations in the coding region of p53 are the most common genetic alteration found in human cancers. Using various mouse models, we have discovered p53 can be activated in stem/progenitor cells of multiple organs, and altered Arf/p53 pathway activity in non-cancerous mouse tissues is relevant to adult stem cell populations. Our findings reveal the importance of the Arf/p53 pathway in tissue homeostasis and regeneration. This work leads to the potential discovery of early events that occur in the carcinogenesis of multiple organs and unravels the role of Arf/p53 in tissue regeneration and carcinogenesis.
