Activities
Dr Amati’s Research Group operates between the European Institute of Oncology and the partner Institution, The Italian Institute of Technology where Dr Amati serves as Director of the Center for Genomic Science of IIT@SEMM
Oncogenic signals induce cell cycle progression and malignant transformation, but concomitantly elicit tumor-suppressive mechanisms (including apoptosis, senescence, and/or DNA Damage Responses), which must be bypassed in order to allow tumor progression, and which constitute the main selective pressure for mutation and/or silencing of tumor suppressor genes. Apoptosis and senescence also determine the therapeutic efficacy of genotoxic treatments (whether chemo- or radio-therapy). Hence, the same genetic lesions and/or epigenetic alterations that allow tumor progression also influence therapeutic responses.
Our group has a long-standing interest in the c-myc oncogene and its product, the Myc protein. Under physiological circumstances, Myc is a central regulator of the cellular responses to extracellular stimuli. When its expression becomes uncontrolled, however, Myc acquires potent oncogenic properties. Myc is a transcription factor: it functions as a heterodimer with a unique partner, Max. The Myc/Max dimer directly or indirectly binds a multitude of target genes, and can either activate or repress transcription.
In general terms, our research aims at explaining the oncogenic activity of Myc, its action on the genome, its effects on cell cycle progression, cell death and differentiation, the tumor suppressor pathways that antagonize it, and their impact on tumor progression and maintenance.
We also use Myc as a paradigm to study the epigenetic organization and regulation of the genome. In particular, we are interested in understanding how specific chromatin environments – or epigenetic states – determine recognition by Myc of its binding sites in the human and mouse genomes, and how Myc further modifies chromatin to regulate gene expression. These studies rely on advanced protocols based on next-generation DNA sequencing technology (ChIP-seq, RNA-seq and others).