René Bernards

René Bernards, PhD is a Professor of Molecular Carcinogenesis and Group Leader at the Netherlands Cancer Institute (NKI-AVL) in Amsterdam. He is a pioneer in using functional genetic screens to identify cancer drug resistance mechanisms and has made foundational contributions to understanding how the Wnt/beta-catenin pathway mediates immune exclusion in tumors. His group performed landmark genome-wide CRISPR screens in syngeneic mouse tumor models and identified active beta-catenin signaling as a key tumor-cell-intrinsic pathway that excludes dendritic cells and T cells from the tumor microenvironment by suppressing CCL4 chemokine secretion. This work provided mechanistic explanation for the immune-excluded phenotype observed in Wnt-high tumors and demonstrated that pharmacological inhibition of beta-catenin can convert immune-cold tumors to immune-hot. Dr. Bernards also pioneered the concept of synthetic lethality in cancer drug resistance, and his laboratory has conducted extensive CRISPR-based screens to identify resistance genes for EGFR inhibitors, BRAF inhibitors, and checkpoint immunotherapy, generating the most comprehensive functional genomics maps of treatment resistance in solid tumors.