The research line in Genomic Science applies modern genomic technologies towards a better understanding of complex biological processes and diseases, with particular emphasis on Cancer.Our line is located within the IFOM-IEO Campus in Milan, one of the largest and most vibrant cancer research communities in Europe. Our laboratories provide state-of-the art technological platforms for functional genomics, and benefits from all the infrastructure, technological platforms and didactic activities already present in the IFOM-IEO Campus. Our PhD program is integrated with that of SEMM, the European School of Molecular Medicine.
Our mission is to identify changes in the genome that underlie the development of cancer, as well as its susceptibility to therapeutic intervention. Our general aim is to reduce pathological traits into their molecular components, which might correspond to disease markers or potential targets for pharmacological intervention. We will exploit these molecular markers and targets in order to build up strategic programs for disease prevention, early detection and treatment.
Genomic Science co-directs, together with IEO, a cutting edge Genomic Unit for high-throughput sequencing, run by dedicated personnel and equipped with state-of-the-art technologies, including NovaSeq 6000 and HiSeq 2000 Illumina machines. For the computational requirements of this unit and the Center research activities, we have access to a cluster system equipped with 336 cores and 1.2 PB of storage space.
Our research line includes three units
We study the function and regulation of non-coding transcripts (microRNAs – miRNAs, and long non-coding RNAs – lncRNAs), with a particular focus on how regulatory RNAs shape the identity and properties of mammalian cells. We are particularly interested in i) the role played by degradation mechanisms in miRNA regulation and the interplay with RNA targets (Target-Mediated miRNA degradation - TDMD), both in physiology and cancer; ii) key transcriptional and epigenetic circuitries that are mediated by noncoding RNA (miRNA and lncRNA) and able to determine the identity and plasticity of epithelial cells; iii) RNA-based agents with diagnostic or therapeutic potential amenable to clinical use.
We are studying how transcription factors regulate gene expression by using next generation sequencing strategies and genetically modified animal models. We are focusing on (i) the identification of transcription factor networks high-jacked by oncogenes during cell transformation, (ii) pharmaco-genomic studies to understand the molecular basis and mechanism of action of small molecules targeting transcriptional complexes and epigenetic regulators, (iii) understanding how oncogenic transcription affect genome stability.
We employ an interdisciplinary approach, based on mathematical modeling of cutting edge genomics data, to study the dynamics of transcription (including the synthesis, processing and degradation of RNAs). Specifically, we aim at deciphering (i) how transcriptional dynamics are influenced by RNA modifications and chromatin-associated factors, and (ii) how they are altered in cancer.
- We have applied new tailored approaches based on in vivo RNA labeling and high-throughput sequencing to the study of miRNA degradation mechanisms, thus highlighting the importance of decay dynamics in the regulation of the miRNA pool (DOI).
- We have developed a computational tool (termed IsomiRage) able to identify, analyse and classify miRNA isoforms (called “isomiRs” from NGS data (DOI).
- Identification of compensatory RNApolII loading on promoters explains the selective efficacy of Brd4 inhibitors in Myc driven cancers. (DOI1, DOI2).
- Discovery of a mechanism of transcriptional regulation, which reinforces Myc dependent transcription and allows integration of chemical and physical cues, directly on promoters and enhancers, to regulate cell division. (DOI).
- We develop experimental and computational methods to quantify the kinetic rates governing the main steps in the RNA life cycle (RNA synthesis, processing and degradation), collectively defining the dynamics of each transcript (DOI1, DOI2).
- We use an interdisciplinary approach – based on metabolic labeling of nascent RNA, epitranscriptome profiling and their integrative analysis through mathematical modeling - to study the functional role of RNA dynamics in tumors with high-levels of the MYC oncogene (DOI1, DOI2).
- Dr. Ana Marques, University of Lausanne - Lausanne, Switzerland
- Dr. Davide De Petri Tonelli, IIT - Genova, Italy
- Dr. Tiziana Bonaldi, IEO - Milan, Italy
- Prof. Johannes Zuber, Research Institute of Molecular Biology (IMP) - Vienna, Austria
- Prof. Pier Giuseppe Pelicci, IEO – Milan, Italy
- Dr. Bruno Amati, IEO – Milan, Italy
- Dr. Benedetto Grimaldi, IIT – Genova, Italy