Luca Cartegni, PhD

Enlarge Image Splicing signals and modes of alternative splicing. Top: Conserved motifs at the exon/intron boundaries are shown. The size of the nucleotide at a certain position is proportional its frequency. Nucleotides that contribute to the consensus motive are shown in yellow, the branch point in orange. Bottom: five common modes of alternative splicing, with different paths indicated in green and red. Multiple modes can apply in combination to the same transcripts, and additional isoforms can be generated by alternative usage of promoters and PolyA sites. Alternative splicing is one of the main mechanisms used by the cell for the regulation of gene expression in response to changing intracellular and extracellular stimuli. It also partially accounts for how the complexity of the proteome can be achieved by the relatively small number of human genes. Maintenance of stage- and cell-type-specific splicing patterns is key to the normal functioning of the cell and is a level of control that is frequently dysregulated in cancer cells, with the appearance/selection of splicing variants that contribute to the aberrant phenotype. The main interest of my lab is to identify alternative splicing events that play a role in the development and/or maintenance of cancer, to study the cis and trans effectors involved, to understand what causes the loss of tight splicing control in cancer cells, and, ultimately, to develop means to control such events in a therapeutic perspective.