Cancer Biology

Cancer represents a collection of pathologies characterized by the selective accumulation of alterations in the genome (point mutations, rearrangements, amplifications, deletions) and the epigenome (DNA methylation and histone modifications) leading to aberrant cellular proliferation. In this context, genetically modified mouse models that faithfully recapitulate tumor progression are invaluable for the identification of (epi-) genomic alterations causally involved in cancer etiology.

We are focusing on:

1.The establishment of novel mouse models based on genetic modification of somatic stem cells and progenitors, to allow rapid generation of genetically engineered mice faithfully recapitulating human cancers.

2. Genetic and epigenetic analysis of tumor progression in vivo to map genetic and genomic alterations selected for during tumor progression. With this approach we aim to identify novel tumor suppressors, oncogenes and pathways selectively activated in cancer cells.

3. Functional characterization of the oncogenes, tumor suppressors and potential molecular targets we identify.

4. Reverse genetics in tumor models based on viral shRNA libraries and genome wide transposon-mediated insertional mutagenesis.

5. Development of high-throughput screens based on high-content cellular imaging to identify molecular targets for cancer therapy.

Laboratories

We have access to advanced technological services (all basic requirements for molecular/cellular biology are present). IIT@SEMM focuses on Genomic Science and in particular Cancer Genomics (http://genomics.iit.it). We have created an advanced Genomic Unit, which allows routine use of next-generation DNA sequencing (Illumina HiSeq) and NanoString technology. Our Computing Unit ensures data-flow from the sequencing platforms to the servers and advanced computational analysis, in conjunction with a rich community of computational scientists.

Collaborations

Dr. Mark Wade (Screening Unit, Center for Genomic Science of IIT@SEMM)

Dr. Bruno Amati (Oncogenes, Chromatin and Gene Regulation, Center for Genomic Science of IIT@SEMM)

Dr. Mattia Pelizzola (Computational Epigenomics, Center for Genomic Science of IIT@SEMM)

Dr. Francesco Nicassio (MicroRNAs and non-coding RNAs in stemness, proliferation and differentiation, Center for Genomic Science of IIT@SEMM)

Selected Pubblications

1. Rohban S, Campaner S. Myc induced replicative stress response: How to cope with it and exploit it. Biochim Biophys Acta. 2015 May; 1849 (5):517-24. doi: 10.1016/j.bbagrm.2014.04.008.

2. Sabò A, Kress TR, Pelizzola M, de Pretis S, Gorski MM, Tesi A, Morelli MJ, Bora P, Doni M, Verrecchia A, Tonelli C, Fagà G, Bianchi V, Ronchi A, Low D,

Müller H, Guccione E, Campaner S, Amati B. Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis. Nature. 2014 Jul 24;511(7510):488-92. doi: 10.1038/nature13537.

3. Murga M*, Campaner S*, Lopez-Contreras AJ, Toledo LI, Soria R, Montaña MF, D'Artista L, Schleker T, Guerra C, Garcia E, Barbacid M, Hidalgo M, Amati B,

Fernandez-Capetillo O. Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors. Nat Struct Mol Biol. 2011 Nov 27; 18 (12):1331-5. doi: 10.1038/nsmb.2189.

4. Campaner S, Spreafico F, Burgold T, Doni M, Rosato U, Amati B, Testa G. The methyltransferase Set7/9 (Setd7) is dispensable for the p53-mediated DNA damage response in vivo. Mol Cell. 2011 Aug 19;43(4):681-8. Doi: 10.1016/j.molcel.2011.08.007.

5. 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, Amati B. Cdk2 suppresses cellular senescence induced by the c-myc oncogene. Nat

Cell Biol. 2010 Jan; 12 (1):54-9; sup pp 1-14. doi: 10.1038/ncb2004.