SILVIA FRE

Doctor,
Research Director Inserm
Recherche - Paris
Spécialités / domaines
Developmental biology,
Development, cancer, genetics and epigenetics,
Signalling
Présentation

In spite of the great advances of developmental biology in the past years, the mechanisms underlying morphogenesis and homeostasis of adult organs remain only superficially understood. Somatic stem cells are critical players during developmental growth and for maintaining adult tissue homeostasis.

The main focus of our research is understanding how tissue-specific stem cells engage in differentiation while retaining self-renewal potential and plasticity.

We study stem cells and the signals that orchestrate cell fate specification, both during physiological tissue development and homeostasis as well as in tumours. We use an interdisciplinary approach combining in vivo clonal analysis by lineage tracing with time-lapse analysis of 3D organotypic cultures and intravital imaging, whole mount immunofluorescence, barcoding and transcriptomic analyses and mathematical modelling of clonal dynamics. Our projects use Notch expression and activity as tools to characterize stem/progenitor cells, but are also aimed at revealing if mechanistically Notch signals can change the fate of normal and cancer stem cells.

Understanding the dynamic behaviour and the transcriptional signatures of stem and progenitor cells will provide insights into the molecular regulatory mechanisms controlling organ maintenance, repair and regeneration, which will form the basis for the development of safe and efficient therapeutic applications of stem cells in regenerative medicine. In addition, we are testing the hypothesis that neoplastic transformation of stem cells could be the initiating event in certain tumour types. These functional studies have important implications for understanding cell plasticity in vivo and to clarify how reactivation of embryonic developmental programs in adult cells could lead to cancer.

Publications
Impaired PRC2 activity promotes transcriptional instability and favors breast tumorigenesis
Genes & Development
Michel Wassef, Veronica Rodilla, Aurélie Teissandier, Bruno Zeitouni, Nadege Gruel, Benjamin Sadacca, Marie Irondelle, Margaux Charruel, Bertrand Ducos, Audrey Michaud, Matthieu Caron, Elisabetta Marangoni, Philippe Chavrier, Christophe Le Tourneau, Maud Kamal, Eric Pasmant, Michel Vidaud, Nicolas Servant, Fabien Reyal, Dider Meseure, Anne Vincent-Salomon, Silvia Fre, Raphaël Margueron
Mechanical induction of the tumorigenic β-catenin pathway by tumour growth pressure
Nature
María Elena Fernández-Sánchez, Sandrine Barbier, Joanne Whitehead, Gaëlle Béalle, Aude Michel, Heldmuth Latorre-Ossa, Colette Rey, Laura Fouassier, Audrey Claperon, Laura Brullé, Elodie Girard, Nicolas Servant, Thomas Rio-Frio, Hélène Marie, Sylviane Lesieur, Chantal Housset, Jean-Luc Gennisson, Mickaël Tanter, Christine Ménager, Silvia Fre, Sylvie Robine, Emmanuel Farge
Concomitant Notch activation and p53 deletion trigger epithelial-to-mesenchymal transition and metastasis in mouse gut
Nature Communications
Maia Chanrion, Inna Kuperstein, Cédric Barrière, Fatima El Marjou, David Cohen, Danijela Vignjevic, Lev Stimmer, Perrine Paul-Gilloteaux, Ivan Bièche, Silvina Dos Reis Tavares, Giuseppe-Fulvio Boccia, Wulfran Cacheux, Didier Meseure, Silvia Fre, Loredana Martignetti, Patricia Legoix-Né, Elodie Girard, Luc Fetler, Emmanuel Barillot, Daniel Louvard, Andreï Zinovyev, Sylvie Robine