Iannis Aifantis

Iannis Aifantis has made transformative contributions to understanding NOTCH1 as an oncogene in T-cell acute lymphoblastic leukemia, elucidating how activating NOTCH1 mutations occur in over 50% of T-ALL cases and drive leukemogenesis through MYC activation and metabolic reprogramming. His research revealed that NOTCH1 directly binds to the MYC enhancer to drive MYC transcription, establishing the NOTCH1-MYC axis as the central oncogenic program in T-ALL. He showed that Notch signaling regulates epigenetic landscape changes in leukemia stem cells through H3K27 acetylation at enhancers. His work has defined Notch-driven transcriptional programs as therapeutic vulnerabilities in hematological malignancies.