Deciphering the mechanisms of epigenetic evolution driving leukaemia

My research seeks to understand how epigenetic lesions and epigenetic diversity contribute to tumour initiation and progression, and more specifically, how these epigenetic errors can lead to leukaemia. Cells in an individual tumour can vary markedly in their epigenetic states and transcriptional outputs, enhancing its ability to adapt under various conditions and proliferate faster. I will use state-of-the-art single-cell sequencing technologies to analyse individual cancer cells, characterizing their epigenetic errors (epimutations) and the genes that are activated (transcriptome) during its evolution. I will then introduce epimutations in normal blood cells to mimic cancer cell properties. This will enable me to identify which of those errors drive leukaemia progression. This integrated and innovative approach will contribute to our fundamental understanding on how cells acquire epigenetic aberrations and evolve to give rise to leukaemia, and will inform new therapeutic strategies to target epigenetic lesions in cancer patients.