Rafael Casellas

Rafael Casellas has elucidated how CTCF functions as the master architectural protein organizing the 3D genome through its role as an insulator blocking enhancer-promoter communication across chromatin domains, and how CTCF dysfunction contributes to cancer. His laboratory demonstrated that CTCF binding sites mutated in cancer allow enhancer leakage across TAD boundaries, activating oncogenes that are normally insulated from nearby enhancers. He has shown that DNA methylation at CTCF sites in IDH-mutant gliomas disrupts CTCF binding and boundary function. His work on CTCF in V(D)J recombination revealed how 3D genome organization directs programmed genomic rearrangements, with implications for understanding chromosomal translocations in lymphoid malignancies.