The team: PI: Marina Mapelli; dottorandi: Susanna Eli, Cristina Renna; postdoc: Cristina Cecchetti, Federico Donà, Edoardo Gelardi, Laura Pirovano, Francesca Rizzelli.
Description: Research in our group deals with the structural and functional characterization of molecular mechanisms of stem cell self-renewal and asymmetric cell divisions. The connection between deregulated stem cell divisions and tumorigenesis has been an important findings of the last decades. The notion that tumours could be initiated and maintained by their own stem cells emerged in the 1970s from genetic screens, and was later stregthened by the evidence that deregulated stem cells are a major cause of relapse and resistance to traditional anticancer therapies. In this context, we are interested in understanding the molecular mechanisms governing asymmetric stem cell divisions and fate choice, under normal and pathological conditions. To address these biological questions, we use a combination of high-resolution X-ray crystallography, cryo-Electron Microscopy, biochemical analyses on reconstituted protein complexes and stem cell biology in organoids. Our research activity is organised in three main research lines: 1) studies of complexes coordinating oriented epithelial cell divisions; 2) interplay between niche contacts and fate asymmetry, specifically for Wnt-dependent niches; and 3) implications of self-renewal in cancer development, with focus on intestinal cancers.