Grant: Project Grant

During embryonic development, pluripotent stem cells play a fundamental role in creating the wide variety of tissue types in our bodies. More specialised stem cells are also critical in ensuring that tissues maintain an ability to repair themselves following injury throughout life. One of the fundamental properties of stem cells that has been revealed over the last decade is their ability to acquire new characteristics and adapt to the surrounding microenvironment. This process is known as cellular plasticity and implies that the stem cell state is not fixed in time. In fact, we now know that virtually all cells may acquire stem cell attributes if exposed to the appropriate cues. Our research team has developed unique expertise in unraveling the signals that govern stem cell plasticity in the developing and regenerating intestinal epithelium, one of the most highly proliferative tissues known in the human body. Our data suggests that epithelial cells in the gut transition from an adult to a fetal state in response to a wide range of environmental triggers. With this knowledge, we aim to study the molecular mechanisms regulating fetal progenitor cells during gut morphogenesis and their relation to regenerative stem cells activated following intestinal injury. Finally, we will investigate the role of fetal-like stem cells during colorectal cancer progression. To pursue these aims we will exploit genetically modified mouse models as well as patient-derived tumor cell cultures. We anticipate that this proposal may lead to novel strategies that promote tissue regeneration in the context of inflammatory bowel disease, as well as identify vulnerabilities of colorectal cancer cells that can be targeted therapeutically.