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.
As Dr. Hsieh specializes in treating kidney cancers, the Hsieh laboratory will expand its research scope to establish a translational kidney cancer research component. The translational program will utilize patient materials to directly decode the molecular basis underlying treatment response and cancer metastasis, thus offering personalized treatment regimens. Furthermore, through building the molecular blueprint of kidney cancer pathogenesis, we wish to develop novel mechanism-based therapeutics to better treat and eventually cure kidney cancer patients.
Chen DY, Lee Y, Van Tine BA, Searleman AC, Westergard TD, Liu H, Tu HC, Takeda S, Dong Y, Piwnica-Worms DR, Oh KJ, Korsmeyer SJ, Hermone A, Gussio R, Shoemaker RH, Cheng EH, Hsieh JJ. 2012 A Pharmacologic Inhibitor of the Protease Taspase1 Effectively Inhibits Breast and Brain Tumor Growth. Cancer Research, 72(3), 736-746.
Hakimi A, Chen Y, Wren J, Gonen M, Abdel-Wahab O, Heguy A, Liu H, Takeda S, Tickoo SK, Reuter VE, Voss MH, Motzer RJ, Coleman JA, Cheng EH, Russo P, and Hsieh JJ. Clinical and Pathologic Impact of Select Chromatin Modulating Tumor Suppressors in Clear Cell Renal Cell Carcinoma. European Urology, 2012, 63, 848-854.
Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer. Vanharanta S, Shu W, Brenet F, Hakimi AA, Heguy A, Viale A, Reuter VE, Hsieh JJ, Scandura JM, Massagué J. Nat Med. 2012. 19, 50-56.
PUMA and BIM Are Required for Oncogene Inactivation-Induced Apoptosis. Bean GR, Ganesan YT, Dong Y, Takeda S, Liu H, Chan PM, Huang Y, Chodosh LA, Zambetti GP, Hsieh JJ, Cheng EH. Sci Signal. 2013 Mar 26;6(268):ra20. doi: 10.1126/scisignal.2003483.
Adverse Outcomes in Clear Cell Renal Cell Carcinoma with Mutations of 3p21 Epigenetic Regulators BAP1 and SETD2: a Report by MSKCC and the KIRC TCGA Research Network.Hakimi AA, Ostrovnaya I, Reva B, Schultz N, Chen Y, Gonen M, Liu H, Takeda S, Voss MH, Tickoo SK, Reuter VE, Russo P, Cheng EH, Sander C, Motzer RJ, and Hsieh JJ for The ccRCC Cancer Genome Atlas (KIRC TCGA) Research Network investigators. Clin Can Res. 2013, 19, 3259-67.
Johns Hopkins Young Investigator Award (1996)
HHMI Physician Scientist Award (2000)
NCI Howard Temin Award (2003)
Cloned Taspase1, a Novel Protease (2003)
Scholar Award, American Society of Hematology (2006)
Scholar Award, American Cancer Society (2009)
Member, American Society for Clinical Investigation (2010)
Founder/Director, the MSKCC Translational Kidney Cancer Research Program (2011)