Group Leader: Bruno Amati, Director
Our group has a long-standing interest in the c-myc oncogene and its product, the transcription factor Myc. Under physiological circumstances, Myc is a central regulator of the cellular responses to extracellular stimuli but, when its expression becomes uncontrolled, Myc acquires potent oncogenic properties. At the molecular level, Myc functions as a heterodimer with a unique partner, Max. Myc/Max dimers associate with target genes either directly through sequence-specific DNA-binding, or indirectly through protein-protein interactions, and can either activate or repress transcription. Research in recent years has shown that Myc binds thousands of target loci in the genome, but only subsets of these loci are deregulated in any particular cell type or environment, indicating that Myc regulates transcription in a context-dependent manner. It has also become evident that Myc is a central regulator of non-coding RNA species, such as miRNAs, which can have a profound impact on cellular growth control and tumor progression. Finally, we have learned that Myc's access to its target genes depends upon a pre-existing active chromatin configuration, and that Myc further modulates important features of chromatin (such as histone modifications or remodeling). Hence, a full understanding of Myc's activity will require an integrated analysis of RNA (the transcriptome) and chromatin profiles (the epigenome) in both normal and cancer cells.
Our group tackles this question in diverse biological systems, ranging from cultured cells to transgenic mouse models that allow us to follow different stages of tumor progression in vivo. Our studies combine advanced molecular genetic and cell biological tools with state-of-the-art (epi-) genomic approaches (based on "next generation" DNA sequencing technology), as well as reverse-genetic screens (based on high-throughput RNA interference technology). Our general aim is to understand not only the oncogenic activity of Myc, but also the tumor suppressor pathways that antagonize it (e.g. apoptosis, senescence, and/or DNA Damage Responses) and their impact on cancer progression and/or therapy.
Bruno Amati, Director
Andrea Bisso, Post Doc
Arianna Sabò, Researcher
Lucia Casoli, PhD Student
Alessandra Tesi, PhD Student
Paola Pellanda, PhD Fellow
Another part of Bruno Amati's research group operates in the partner institution, the European Institute of Oncology.