My group studies the regulation of adult tissue homeostasis and regeneration using a genetic model system, the adult Drosophila midgut. As in many human tissues, the adult fly midgut undergoes dynamic self-renewal, such that the damaged cells are replaced by new ones generated by resident stem cells, in this case, the intestinal stem cells. Our recent work outlined a simple paradigm for maintaining gut homeostasis in Drosophila. In this feedback model, the loss of mature gut cells induces the expression of cytokines or growth factors, both of them are potent mitogens for intestinal stem cells. Thus, fly intestinal stem cells regulate the generation of new cells according to tissue needs (the degree of mature cells loss) to maintain tissue homeostasis. Similar feedback mechanism of injury-induced compensatory stem cell proliferation might also function in several mammalian tissue regeneration models.
One of the key questions in the feedback model is how are cytokines and growth factors induced in the damaged midgut? A variety of insults, such as enteric infection, oxidative stress, detergent treatment, direct cell elimination or JNK-mediated stress response, can induce the proliferation of intestinal stem cells. It is still an outstanding question how fly midgut senses these diverse types of insults and relay these signals to induce the expression of cytokines and growth factors.
Using a variety of approaches, including gene expression profiling and genetic screens, we are also interested in identifying new genes or pathways involved in the regulation of fly midgut homeostasis and regeneration. Given the evolutionary homology between the fly midgut and mammalian intestine and colon, genes that are critical for fly midgut homeostasis likely also play important roles in human digestive diseases, such as colorectal carcinoma.
Comparing to its mammalian counterpart, the intestine and colon, Drosophila midgut has a much simpler structure and stem cell lineage. Using the genetic tools available in the fly midgut, we are also interested in addressing some of the fundamental issues in the stem cell field, such as the heterogeneity of stem cells, stem cell’s cytoprotective properties, the regulation of stem cell pool sizes, etc.