Karpowicz Lab

The body is inti­mately con­nected to envi­ron­men­tal factors, and resolv­ing these con­nec­tions is an impor­tant chal­lenge for phys­i­ol­ogy and medicine. The intes­tine is an organ under constant envi­ron­men­tal stress, not only due to food and chemical intake and the harsh process of diges­tion, but also because animals ingest harmful pathogens and harbour a vast micro­biome. The intes­tine provides a barrier between a dan­ger­ous envi­ron­ment and our body, that simul­ta­ne­ously must absorb nutri­ents needed for survival. The intesti­nal epithe­lium is critical and has evolved to regen­er­ate very effectively.

The intes­tine has an incred­i­bly high turnover of cells, perhaps the fastest of any tissue in the body. Intestinal cells are con­stantly replaced through­out the lifetime of all animals. Following injury, the intes­tine tran­si­tions from a state of steady cell turnover into a state of acute regen­er­a­tion, where damaged cells are replaced very quickly. This incred­i­ble capacity for cell pro­duc­tion is driven by stem cells which divide to make all intesti­nal epithe­lial cells.

This system provides a rich and fas­ci­nat­ing area of research. A rel­a­tively unex­plored area is how intesti­nal tissue regen­er­a­tion is timed. What timing under­lies the pro­duc­tion of intesti­nal cells from stem cells? How are these processes con­nected to feeding, injury, and phys­i­ol­ogy? Circadian rhythms are 24 hour cycles that daily occur through­out the body, includ­ing the cells of the intes­tine. We have shown that regen­er­a­tion and stem cells have cir­ca­dian rhythms that coor­di­nate regen­er­a­tion with other daily events.

Circadian rhythms are fun­da­men­tal feature of living organ­isms, and they are driven by a genetic pace­maker called the cir­ca­dian clock. This clock is set by day/night cycles, normally caused by the 24 hour rotation of planet Earth, that aligns the body to cycles of envi­ron­men­tal change. Our modern society increas­ingly puts pressure on this system: frequent shift-work and travel across time-zones, late-night snacking and light from our elec­tronic devices before we sleep, and constant changes to our sched­ules every weekday to weekend. These affect the phys­i­ol­ogy of the intes­tine and can lead to disease. Our research studies the intes­tine as a basic model of how daily envi­ron­men­tal cues are prop­a­gated in regen­er­a­tion, and raises impor­tant ques­tions per­ti­nent to society and health­care. This work merges chrono­bi­ol­ogy, phys­i­ol­ogy, and stem cell biology.