Oncogenic RNA metabolism

My lab, with a team of collaborators, contributed to establish the role of mRNA metabolism in sustaining oncogene program expression. We identified the exportin XPO1 as a critical regulator of the export of ribonucleoproteins with oncogenic transcript cargos such as MYC, BCL6 and BCL2 in hemtaologic malignances and solid tumors. By a combination of CRISP-cas9 technologies with RNA-sequencing and iTRAQ-based proteomics we established the mechanism by which different XPO1 mutants sustain oncogenesis. We also defined the mechanism by which eIF4E maintains the expression of oncogenic networks in lymphoma cells by acting at the nuclear level and translational level using a combination of eIF4E RIP-sequencing and polysomal profiling under several treatment conditions. In this work, we showed for the first time the network of transcripts regulated by eIF4E at the nuclear export level. We defining new consensus sequences in the mRNA that make them targets of the eIF4E-LRPPRC-XPO1 system. Several clinical trials in lymphomas testing XPO1 and eIF4E inhibitors alone and in combinations are currently underway at WCM.