Yang Shi

Yang Shi made the landmark discovery of LSD1/KDM1A, the first histone demethylase, overturning the longstanding dogma that histone methylation was an irreversible epigenetic mark and establishing that histone modifications are dynamically regulated by opposing writer and eraser enzymes. This discovery opened the field of histone demethylase biology and revealed that aberrant histone demethylation contributes to cancer gene dysregulation. LSD1 is now recognized as a therapeutic target in acute myeloid leukemia, small cell lung cancer, and other malignancies, with multiple LSD1 inhibitors in clinical development. His conceptual breakthrough that epigenetic marks are reversible provided the mechanistic rationale for epigenetic therapy in cancer.