Karpowicz Lab

Physiological processes are inti­mately con­nected to envi­ron­men­tal cues, and resolv­ing these con­nec­tions is an impor­tant chal­lenge for biology and medicine. The intes­tine is a tissue under constant envi­ron­men­tal stress, not only due to the harsh process of diges­tion, but also because animals ingest harmful pathogens or chem­i­cals often dur­ingth­eir lives. The intes­tine provides a barrier to handle these insults, and simul­ta­ne­ously it must absorb nutri­ents needed for survival. Both func­tions are critical and the intes­tine has evolved to respond to envi­ron­men­tal damage very effectively.
The intes­tine has an incred­i­bly high turnover of cells, perhaps the fastest of any tissue in the body. Cells are con­stantly replaced, even at baseline levels. Following injury, the intes­tine tran­si­tions from this 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 a pop­u­la­tion of 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 turnover is timed. What, if any, timing under­lies the pro­duc­tion of intesti­nal cells from stem cells? How are these processes con­nected to the timing of feeding, injury, or general phys­i­ol­ogy? Circadian rhythms are 24 hour cycles of phys­i­o­log­i­cal change that occur in nearly all cells of the body, includ­ing those of the intestine.
Circadian rhythms are fun­da­men­tal feature of living organ­isms, and they are driven by a genetic pace­maker inside the cells of our body called the cir­ca­dian clock. This clock is set by day/night cycles, normally caused by the 24 hour rotation of planet Earth, but increas­ingly changed in modern society by shift-work, travel across time-zones, and changes to our sched­ules from weekday to weekend. Our research applies the intes­tine as a basic model of how daily envi­ron­men­tal cues are prop­a­gated in the body, and raises impor­tant ques­tions about this work per­ti­nent to society and health­care. To do this, our research merges chrono­bi­ol­ogy, phys­i­ol­ogy, and stem cell biology.