Our Research

Mouse intestine

The Circadian Clock is an ancient and evo­lu­tion­ar­ily con­served pathway present in all animals includ­ing human beings. The study of the timing of intesti­nal regen­er­a­tion is very sig­nif­i­cant to health. We are inter­ested in how the loss of cir­ca­dian rhythms affects inflam­ma­tion, and cancer. A com­bi­na­tion of mouse genetics, cell biology, and genomic methods (RNA-seq, and scRNA-seq) are used to test this system.

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.

Our research is also sig­nif­i­cant in under­stand­ing cancer, par­tic­u­larly col­orec­tal cancer which is higher in shift-workers. Regeneration can lead to cancer because the acti­va­tion of stem cells can turn on genes involved in growth and pro­lif­er­a­tion. We are inter­ested in explor­ing how the growth and division of cells has cir­ca­dian timing, and what happens when this timing is lost. As well, the treat­ment of cancer often results in gas­troin­testi­nal mucosi­tis due to damage of the intesti­nal epithe­lium by chemo- or radiation-therapies. Our research will provide infor­ma­tion to prevent and optimize treat­ments for cancer based on daily timing.

The Intestine in a dish

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. We are using organoids to test specific cellular behav­iours, to test the under­ly­ing genetics, and to apply trans­genic reporters and genomics (RNA-seq) to char­ac­ter­ize this system. Organoids 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.

Drosophila intestine

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 use complex genetic methods, genomics (scRNA-seq and DamID) in Drosophila to discover and char­ac­ter­ize new processes.

We have shown that the Drosophila intes­tine shows cir­ca­dian rhythms in regen­er­a­tion. We have further found that the Circadian Clock is first estab­lished in the stem cells of the intes­tine when it develops. We are inter­ested in using Drosophila to under­stand how cir­ca­dian rhythms influ­ence the regen­er­a­tion and metab­o­lism of the diges­tive tract at the single-cell level.

Stem Cell Reports Vol. II

See more in our pub­li­ca­tions section.