Regulation of stem cell function during tissue homeostasis and transformation. (360G-Wellcome-104103_Z_14_Z)

Stem cells maintain tissue homeostasis by adjusting their function to microenvironmental or niche signals. Deregulation of such signals results in either tissue loss or uncontrolled stem cell proliferation, the latter often associated with cancer. The intestinal epithelium is a paradigm for the study of stem cell biology. The Drosophila adult midgut has remarkable resemblances to the mouse small intestine, including the presence of dedicated stem cells. During my post-doctoral work I developed Drosophila models of intestinal hyperplasia and regeneration, which have uncovered novel mechanisms regulating stem cell proliferation and suggests that the fly midgut could be a useful paradigm to understand the biology of multiple adult self-renewing epithelia. The overall goal of my research is to combine Drosophila genetics with mammalian models systems to understand how cell autonomous and niche-derived signals regulate adult stem cell proliferation in response to damage as well as in tumo urigenesis. In this proposal I aim to: 1-Identify and characterize novel mediators of tissue hyperplasia and damage-induced regeneration in the adult Drosophila midgut. 2-Translate results from Drosophila into mammalian model systems. 3-Characterize the role of G-protein coupled receptor dLGR2/LGR4 as tumour suppressor.