The growth and maintenance of each organ is supported by the stem cells in the resident tissues, which will respond to damage for tissue regeneration. We study the molecular signals that control these biological processes, and what happens when these signals go wrong. In particular, we focus on the Wnt signalling pathway.
Wnt signalling is a highly conserved pathway that plays principle roles in stem cell biology and in cancer. For both, the intestine has emerged as a prime experimental model. In the adult intestine, it is well established that Wnt signalling plays complementary roles in physiology and pathology: it maintains crypt stem cell compartments and, when activated by mutation, it is the cause of colon cancer.
We study how the Wnt pathway is regulated in intestinal stem cell and cancer development. Our goal is to translate the basic stem cell research to the clinic to aid cancer treatment and regenerative medicine.
We use a broad range of research tools to study how intestinal stem cells and cancers are regulated, including in vivo mouse models and ex vivo intestinal organoid cultures. Intestinal organoids, also called "mini-guts", grow 3-dimensionally in a defined condition and will self-organise to form intestinal crypt-villus budding structures with full self-renewal and differentiative potential. We combine the CRISPR gene editing tools with organoids to study the functional significance of specific genes and signaling pathways in vitro. This presents a superior physiological readout compared to classical mono-layer cell line culture for functional studies and for drug screening.