A drug discovery programme targeting cancer-specific RNA modifying enzymes

Tumour heterogeneity poses a major challenge for identifying novel drug targets in cancer. RNA modification pathways promote tumour heterogeneity by modulating active gene expression programs, thus allowing rapid cellular adaptions to environmental changes. This suggests RNA modifications as a unique opportunity to identify novel cancer-specific drug targets.  

This project aims to establish a novel screening approach taking the cancer- and tissue specificity of RNA modifications into consideration. Researchers will leverage combined in vitro and in vivo tumour assays by using a high-throughput targeted CRISPR-based reverse genetic screen in order to identify those RNA modifications contributing to acute myeloid leukaemia and oral/oesophageal cancer. This approach will serve to systematically identify all functionally tumorigenesis-relevant RNA modifications while opening the possibility to be extended to any cancer for which orthotopic transplantation works reliably.