Analyses of the genetic and phenotypic evolution at single-cell level of normal and cancer stem cells
Intra-tumoral genetic and phenotypic heterogeneity is a constant trait of the transformed phenotype and thought to be critical for tumor growth, metastatization and drug resistance. We have recently established robust protocols to investigate simultaneously genetic and transcriptional clonal-evolution by DNA and RNA barcoding at single-cell level. We are applying this technology to the analyses of metastasis formation and the emergence of drug resistance in mouse models (PDX) of human breast cancer and melanoma. Barcoded tumors are simultaneously analysed by WES/WGS, to obtain mutational profiles, bulk and single-cell RNAseq, to obtain transcriptional profiles, and RNA/DNA barcodes, to reconstruct, at single-cell level, the genetic and transcriptomic clonal evolution of tumor cells during metastatization and the emergence of drug-resistance. The proposed PhD project will be dedicated to the integration of mutational, expression and DNA- and RNA-barcode data from the described experimental settings.