The laboratory of James Hsieh focuses on decoding the molecular blueprint of cancers and developing novel cancer therapeutics. The Hsieh laboratory discovered that the cellular oncogene MLL is regulated by site-specific proteolysis, which led to the purification of the responsible protease which they named “Taspase1.” The discovery of Taspase1 initiated a novel class of endopeptidases. Taspase1 is an evolutionarily conserved protease, which cleaves nuclear factors MLL and TFIIA to orchestrate fundamental biological events. It dictates cell fate, cell cycle, and stem and cancer cell biology, and functions as a non-oncogene addiction protease. Accordingly, two ongoing research directions of the Hsieh laboratory are: (1) study the function of MLL and molecularly reconstruct human MLL leukemias; and (2) study the function of Taspase1 in cancer pathogenesis and develop Taspase1 inhibitors for cancer therapeutics.