Oncogenes, Transcription and Cancer

Bruno Amati
Group Leader
bruno.amati@ieo.it | |
Location | Building 13 Floor 1st Via Adamello 16, Milano |
Our research aims at a better understanding of fundamental disease mechanisms and therapeutic opportunities in MYC-driven cancers, with a particular focus on B-cell lymphoma and liver carcinoma.
The MYCproto-oncogene and its product, the MYC transcription factor, have a central role in cellular growth control and oncogenesis. In normal cells, MYCis induced by growth-promoting signals, and in turn regulates genes involved in key cellular responses (growth, proliferation, apoptosis, energy metabolism, biosynthetic pathways, etc…). During tumor development, a variety of oncogenic mutations (affecting either the MYClocus, or upstream signaling pathways) can elicit deregulated MYC expression and, as a consequence, the aberrant implementation of MYC-dependent gene expression programs.MYC-driven tumors show “oncogene addiction”, indicating that MYC itself – and presumably a subset of its target genes – are required for tumor maintenance.
Key questions in the field regard the mechanisms through which MYC regulates transcription, the identity of MYC-regulated genes, their function in growth control and tumorigenesis, as well as their potential as therapeutic targets.
Our research addresses these questions based on a combination of advanced biological models, high-throughput “omic” approaches and computational tools. In parallel with our basic research program, we pursue translational studies aimed at the development and pre-clinical validation of innovative therapeutic strategies.
Most Relevant Publications
-
Bisso A, Filipuzzi M, Gamarra Figueroa GP, Brumana G, Biagioni F, Doni M, Ceccotti G, Tanaskovic N, Morelli MJ, Pendino V, Chiacchiera F, Pasini D, Olivero D, Campaner S, Sabò A, Amati B
Cooperation between MYC and β-catenin in liver tumorigenesis requires Yap/Taz.
Hepatology, 2020
-
Tesi A, de Pretis S, Furlan M, Filipuzzi M, Morelli MJ, Andronache A, Doni M, Verrecchia A, Pelizzola M, Amati B, Sabò A
An early Myc-dependent transcriptional program orchestrates cell growth during B-cell activation.
EMBO Rep, 2019
-
Rava' M, D'Andrea A, Nicoli P, Gritti I, Donati G, Doni M, Giorgio M, Olivero D, Amati B
Therapeutic synergy between tigecycline and venetoclax in a preclinical model of MYC/BCL2 double-hit B cell lymphoma.
Sci Transl Med, 2018
-
Sabò A, Kress TR, Pelizzola M, de Pretis S, Gorski MM, Tesi A, Morelli MJ, Bora P, Doni M, Verrecchia A, Tonelli C, Fag G, Bianchi V, Ronchi A, Low D, Mller H, Guccione E, Campaner S, Amati B
Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis.
Nature, 2014