1985 Degree in Biology at the University of Geneva Switzerland
1990 Ph.D., at Swiss Institute for Experimental Cancer Research (ISREC) and University of Lausanne, Switzerland
1990-93 Post-doctoral research at Imperial Cancer Research Fund (ICRF), London.
1994-99 Junior group leader at ISREC.
1999-2002 Senior group leader at DNAX, Palo Alto, CA.
Since 2003, Division director, Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.

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 activities become uncontrolled, however, Myc acquires potent oncogenic properties (fig. 1). Myc is a transcription factor: it functions as a heterodimer with a unique partner, Max, which itself forms alternative complexes with factors that can antagonize Myc function (fig. 2). The Myc/Max dimer directly or indirectly binds a multitude of target genes, and can either activate or repress transcription (fig. 3).

fig 1fig.3, Myc functions as an activator or repressor of different target genes [+ zoom]

In general terms, our research aims at explaining the oncogenic activity of Myc, the tumor suppressor pathways that antagonize it, and their impact on tumorigenesis. In order to dissect the pathways involved in those biological responses, we rely on a combination of molecular genetics, cell biology and mouse tumor models. We are focusing in particular on the roles of cell cycle regulators (cyclins, cyclin-dependent kinases and their inhibitors), chromatin-modifying enzymes (e.g. histone acetyl- and methyl-transferases) and Myc-target genes.

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 of transcription factor-binding sites in the human and mouse genomes, and how the same transcription factors further modify chromatin to regulate gene expression. These studies combine quantitative chromatin immunoprecipitation (qChIP) protocols, previously developed and optimized in our group, with high-throughput genome analysis tools available at the IFOM-IEO Campus.

1) Taubert S, Gorrini C., Frank S.R., Parisi T, Fuchs M, Chan H-M., Livingston D.M. and Amati, B. (2004) E2F-dependent histone acetylation and recruitment of the Tip60 acetyltransferase complex to chromatin in late G1.Mol Cell Biol. 24, 4546-4556
2) Amati B. (2004) Myc degradation: Dancing with ubiquitin ligases. PNAS 101, 8843-8844
3) Guccione E, Martinato F, Finocchiaro G, Luzi L, Tizzoni L, Dall'Olio V, Zardo G, Nervi C, Loris B, Amati B. (2006) Myc-binding site recognition in the human genome is determined by Chromatin context. Nat Cell Biol. 8, 764-770
4) Squatrito M, Gorrini C, Amati B. (2006) Tip60 in DNA damage response and growth control: many tricks in one HAT. Trends Cell Biol. 16, 433-442
5) Amati B and Sanchez-Arèvalo Lobo V.J. (2007) Myc Degradation: deubiquitinating enzymes enter the dance. Nature Cell Biology 9, 729-732
6) Gorrini C, Squatrito M, Luise C, Syed N, Perna D, Wark L, Martinato F, Sardella D, Verrecchia A, Bennett S, Confalonieri S, Cesaroni M, Marchesi F, Gasco M, Scanziani E, Capra M, Mai S, Nuciforo P, Crook T, Lough J and Amati B. (2007) Tip60 is a haplo-insufficient tumour suppressor required for an oncogene-induced DNA damage response. Nature 448, 1063-1067
7) Guccione E, Bassi C, Casadio F, Martinato F, Cesaroni M, Schuchlautz H, Lüscher B. and Amati B. (2007) Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive. Nature 449, 933-937
8) Martinato F, Cesaroni M, Amati B and Guccione E. (2008) Analysis of Myc-induced histone modifications on target chromatin. PLoS ONE 3, e3650
8) Smith AP, Verrecchia A, Fagà G, Doni M, Martinato F, Guccione E and Amati B. (2009)
A positive role for Myc in TGFβ-induced Snail transcription and Epithelial to Mesenchymal Transition. Oncogene 28, 422-430
9) Campaner S, Doni M, Hydbring P, Verrecchia A, Bianchi L, Sardella D, Schleker T, Perna D, Tronnersjö S, Murga M, Fernandez-Capetillo O, Barbacid M, Larsson LG and Amati B (2010)
Cdk2 suppresses cellular senescence induced by the c-myc oncogene Nature Cell Biology 12, 54-59
10) Pistoni, M., Verrecchia, A., Doni, M., Guccione, E. and Amati, B. (2010)
Chromatin association and regulation of rDNA transcription by the Ras-family protein RasL11a.
EMBO Journal 29, 1215-1224

No projects are available to students for the current accademic year.