Francesca Ciccarelli
Francesca Ciccarelli
affiliation: IEO - Istituto Europeo di Oncologia
research area(s): Genetics And Genomics, Computational Biology
Course: Molecular Medicine: Molecular Oncology and Computational Biology
University/Istitution: Università di Milano, UNIMI-SEMM
Scientific Profile
Since 2005: Group Leader at the European Institute of Oncology, Milan
2005 – 2010: Contract Professor of Bioinformatics at the University of Bologna, Faculty of Biotechnology
2001 – 2005: Research assistant at the EMBL-Heidelberg, Germany
1999 – 2001: Research Fellow at the Istituto Mario Negri Sud, Italy

2003: University of Heidelberg PhD in Natural Science (Magna cum laude), Supervisor: Dr Peer Bork, EMBL Heidelberg, Germany
1998: University of Bologna Master’s Degree (Laurea) in Pharmaceutical Chemistry (110/110 cum laude), Supervisor: Prof Maurizio Recanatini, Dept of Pharmaceutical Chemistry, University of Bologna
Our research focuses on the role of genomic instability and somatic mutations in the development of human cancer. We use a combination of experimental and computational methods to sequence and analyze genomic data. Two main lines of investigations are currently pursued in the lab:

1. Measure of genomic instability and cancer genome re-sequencing using next generation sequencing (NGS)
We fully exploit the potential of NGS to identify cancer specific somatic mutations and to measure genomic instability. In the past years, we developed a procedure for the quantification of genomic instability that is based on the parallel sequencing of thousands single DNA filaments using NGS. We were able to identify constitutional genomic instability in individuals with heterozygous mutations in MMR genes even before they develop cancer, thus suggesting that they have a predisposition to acquire the second hit that starts tumorigenesis (De Grassi et al. PLoS Biology 2010). Currently, we are focusing in the identification of low-frequency cancer mutations with the aim of rebuilding the proliferation dynamics of cancer. We are also involved in several collaborative efforts of re-sequencing the whole exome of cancer samples to identify cancer-specific mutations.

2. Network Biology and Systems Level Properties of Cancer Genes
Massive cancer genome re-sequencing projects have so far led to the identification of more than 1000 genes with putative cancer driver mutations, and the list is likely to grow. The majority of these genes are mutated in only a tiny fraction of samples, while recurrent mutations are overall very few. This unexpectedly high heterogeneity suggests that the genetic routes to tumorigenesis may be in fact much more intricate. In this complex context, systems biology, that is the study of cancer genes in relationship with the biological systems they interact with, may result of some help (Ciccarelli, BMC Biology 2010). In the past years, our lab undertook a systematic study of the systems-level properties of cancer genes in the attempt of finding recurrent features that could explain their involvement in cancer. We showed that cancer genes overall avoid duplications when compared to the rest of human genes, even when only genes with the same functional properties are considered. In addition, cancer genes tend to encode central hubs, i.e. they preferentially produce singleton proteins that engage several connections and occupy central positions at the crossroads of multiple biological processes. These properties are uncommon within the human gene repertoire and help in interpreting the effect of somatic mutations as a sign of a broader fragility of cancer genes towards perturbations (Rambaldi et al., Trends in Genetics 2008, D’Antonio et al., PLoS Comp Biol 2011). Interestingly, these properties are not limited to well-known cancer genes but are also shared by genes whose modifications have been identified through large-scale mutational screenings (Syed et al., Nucleic Acid Research2010). Currently, we are extending our research to genetic interactions of cancer genes and to the role that gene duplicability may play also in this context.
Genomic Instability and Cancer Genome Re-sequencing
1. De Grassi A, Ciccarelli FD Tandem repeats modify the structure of primate-specific genes expanding in the human population (2009) Genome Biol 10:R137 Highly Accessed
2. Solda' G, Suyama M, Pelucchi P, Boi S, Guffanti A, Rizzi E, Bork P, Tenchini ML, Ciccarelli FD Non-random retention of protein-coding overlapping genes in Metazoa (2008) BMC Genomics 9:174-186 Highly Accessed
3. Fumasoni I, Meani N, Rambaldi D, Scafetta G, Alcalay M, Ciccarelli FD Family expansion and gene rearrangements contributed to the functional specialization of PRDM genes in vertebrates (2007) BMC Evol Biol 7:187-199
4. De Grassi A, Segala C, Volorio S, Bertario L, Radice P, Bernard L, Ciccarelli FD Ultra-deep Sequencing of a Human Ultraconserved Region Reveals Somatic and Constitutional Genomic Instability (2010) PLoS Biology 8: e1000275

Network Biology and Systems Level Properties of Cancer Genes:
1. D’Antonio M Ciccarelli FD Modification of gene duplicability during the evolution of protein interaction network (2011) PLoS Comp Biol 7(4): e1002029.
2. Ciccarelli FD The (r)evolution of cancer genetics (2010) BMC Biology 8:74 Invited commentary Highly Accessed
3. Anelli V, Santoriello C, Distel M, Köster RW, Ciccarelli FD, Mione M Global repression of cancer gene expression in a zebrafish model of melanoma is linked to epigenetic regulation (2010) Zebrafish 6:174-186
4. Syed A, D'Antonio M, Ciccarelli FD Network of Cancer Genes: a Web Resource to Analyze Duplicability, Orthology and Network Properties of Cancer Genes (2010) Nucleic Acids Res 38:D670
5. Rambaldi D, Ciccarelli FD FancyGene: interactive visualization of gene structures and protein domain architectures on genomic loci (2009) Bioinformatics 25:2281
6. Rambaldi D, Giorgi FM, Capuani F, Ciliberto A, Ciccarelli FD Low duplicability and network fragility of cancer genes (2008) Trends Genet 24:427-30
Project Title:
Projects will be discussed directly with the group leader
Research projects are available in both areas of investigation.