Ricerc@Sapienza

I am interested in molecular mechanisms controlling cell plasticity. In particular I focused my investigation on mechanisms controlling cell differentiation, epithelial-to-mesenchymal transition and tumour onset and dissemination. My collaborators and I elucidated the role of MyoD in the control of p57 (a cyclin-dependent kinase inhibitor) during muscle differentiation through the direct binding to the chromatin, and of CTCF in the reorganization of chromatin structure in the same phenomenon. In three recent studies, I projected, developed and then elucidated with my team members the role and regulation of a lncRNA, HOTAIR, in the progression of epithelial-to-mesenchymal transition. Specifically, I found that this lncRNA binds to the chromatin, together with the transcriptional factor Snail, in order to recruit chromatin modifiers on the promoters of epithelial genes. Then I focused on its transcriptional regulation, mainly mediated by another transcriptional factor, HNF4a, that binds to its promoter and enhancer and modifies a higher-order chromatin structure promoting HOTAIR transcription. More recently I designed a strategy to counteract HOTAIR function in epithelial-to-mesenchymal transition through an RNA-based approach counteracting HOTAIR-Snail interaction and chromatin modifications on the promoter regions of Snail-target epithelial genes.

I am presently involved in research projects related to the identification of RNA-binding proteins interacting with microRNAs and responsible for microRNAs loading inside extracellular vesicles, specifically into exosomes. In this scenario I am also investigating the role of epitranscriptomics in modulating microRNA-protein interaction both in epithelial-to- mesenchymal transition and during differentiation.

Moreover, I have been implicated in the development and biological application of different epigenetic drugs able to modulate gene expression both in epithelial-to-mesenchymal transition and in tumorigenesis. With respect to this aspect, I focused on the use different inhibitors of chromatin modifiers (DNA methyltransferases, Histone deacetylases, Polycomb repressive complex 2) in order to verify whether they could restore epithelial cell features (and epithelial genes expression rescue) without affecting transcription factor binding to the promoters of several epithelial genes.