The study of intestinal regeneration is very significant to human health. Our work helps understand what happens in patients which have inflammatory diseases such as Crohn’s Disease or Ulcerative Colitis. As well, the treatment of cancer often results in gastrointestinal mucositis, a damaging of the intestinal epithelium by chemical agents. Understanding intestinal regeneration will help treat or avoid these side effects. Finally, regeneration can lead to cancer because the activation of stem cells turns on genes involved in growth and proliferation. Thus we are interested in exploring the relationships between healing and tumorigenesis.
The Circadian Clock is an ancient and evolutionarily conserved pathway. We are interested in studying how time of day regulates regeneration in mammals, such as mice, and how this is connected to inflammation, growth and cancer.
The intestine and colon can be readily grown in cell culture in the form of intestinal “organoids”. These organoids are artificial ‘miniguts’ that arise from stem cells harvested from animal tissues. Organoid assays enable us to study the physiology of animals without using the animals themselves.
We derive organoids from mice and human biopsies as an exciting new model system to complement our animal-based work. These allow sophisticated cell-based experiments to study the interactions between the cells making up the intestinal epithelium. In particular, we are interested in using human organoids to study the regeneration and circadian biology of the human small intestine and colon. Such experiments cannot be done on human beings themselves.
The genetic tractability of Drosophila makes it an excellent model system to investigate complex cellular interactions. Functional genetic screens can be carried out in Drosophila to discover new genes. These can be investigated in other animals where they are often conserved. We are interested in using Drosophila as a tool to discover and characterize new processes.
Surprisingly, the intestine shows a daily rhythm in cell regeneration, which means that healing is activated according to time of day. This requires the Circadian Clock, a molecular pathway that is synchronized by daylight in all animals. We are interested in using Drosophila to understand how light/dark cycles influence the regeneration of the intestine.
Stem Cell Reports Vol. II
See more in our publications section.