A central pillar of our research program is our in vitro screening platform, which we deploy to systematically search and characterize genotype-specific actionable vulnerabilities in lymphoma. For that purpose, we have collected more than 350 distinct cancer cell lines, for which we have exome and transcriptome sequencing data available. We deploy this cell line panel for large-scale pharmaco-genomic screens, as well as drug synergy screens. We have further implemented CRISPR screening technology, to conduct CRISPR dropout, as well as CRISPRa and CRISPRi screens. Together, these technologies enable systematic vulnerability screens in well-annotated cancer genomic contexts. These screens lay the foundation for subsequent mechanistic studies, as well as in vivo validation experiments. Moreover, these screens inform subsequent model generation and design.