Transcriptional and post-transcriptional control mechanisms in cancer
Cancer evolution is driven by the selection of genetic, epigenetic and transcriptional alterations that support oncogenic programs, disengage tumor suppressive pathways, favor adaptation to the tumor microenvironment and foster resistance to therapies. We are studying transcriptional and post-transcriptional regulatory programs in order to understand the mechanisms controlling these key properties of cancer cells. We exploit the latest genomic technologies at population (including RNA-seq, ATAC-seq, 4-SU-seq, and TIDE-seq), single cell (scRNA-seq, scATAC-seq) and single molecule level (Nanopore). Reverse genetics studies, based on gene silencing and genome editing (i.e. shRNA or CRISPR libraries), are used for functional and preclinical validation. We aim at identifying key transcription factors and their essential effectors, unraveling the mechanisms controlling aberrant transcription in cancer cells (transcriptional addiction, enhancers hijacking, alternative splicing, dynamics of RNA processing and decay) and defining cancer cells vulnerabilities (therapeutic targets).
Impact on human disease: a detailed knowledge of how cancer cells process genetic information will instruct the development of targeted therapeutics and new diagnostics (molecular signatures and biomarkers).