Xiaodong Cheng

Xiaodong Cheng has made milestone contributions to the structural biology of DNA methyltransferases, solving crystal structures of DNMT3A, DNMT3B, and DNMT1 that revealed the molecular mechanisms of de novo and maintenance DNA methylation with atomic-level detail. His structural studies showed how the DNMT3A R882H mutation found in acute myeloid leukemia disrupts the enzyme's tetrameric assembly and alters its activity, explaining the dominant-negative mechanism of this common cancer mutation. He has characterized the structural basis for DNMT-chromatin interactions that target methylation to specific genomic regions. His structural insights have guided the design of next-generation DNMT inhibitors with improved selectivity and potency for cancer epigenetic therapy.