Crosetto Lab

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Our mission is to develop and apply quantitative approaches to understand the fundamental mechanisms that drive cancer initiation and progression, and translate these approaches to the clinic in order to achieve personalised cancer care. Specifically, we focus on two main research areas:

1. Genome fragility and architecture

We are interested in understanding how the 3D architecture of the genome shapes the higher propensity of DNA to break in certain regions. In particular, we are interested in understanding how chromatin dynamics throughout the cell cycle and the interplay between DNA replication and transcription are linked to the formation of DNA double-strand breaks (DSBs) along the genome. We have pioneered the first method, BLESS, for mapping the genomic location of DSBs (Crosetto et al, Nat Meth 2013), and recently we have developed a powerful improvement, BLISS, which allows quantitative genome-wide analysis of DSBs even in low-input samples (Yan et al, Nat Commun 2017). We combine DSB detection methods with state-of-the-art chromosome conformation capture assays (HiC), high-resolution DNA and RNA in situ fluorescence hybridization methods (Bienko, Crosetto et al, Nat Meth 2013), and methods newly developed in our lab that interrogate the radial positioning of chromosomes in the cell nucleus.

2. Quantitative cancer pathology

We are interested in developing quantitative approaches to measure genetic, transcriptional, and phenotypic intra-tumor heterogeneity with the aim of reconstructing tumor evolution and improving patient classification and therapy selection. To do so, we combine microscopy (Annaratone et al, Oncotarget 2017) and sequencing technologies with advanced computational tools (Topological Data Analysis), and apply them to tumor samples obtained from our collaborators at the Karolinska University Hospital and from other centres in Europe (IRCCS Candiolo in Turin and IEO in Milan, Italy) and the US (MD Anderson Cancer Center).

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