James J. Hsieh, M.D., Ph.D.

Internal Medicine
Developmental Biology

Molecular Genetics and Genomics Program
Developmental, Regenerative and Stem Cell Biology Program
Molecular Cell Biology Program

Research Abstract:

As a medical student taking care of cancer patients in 1990, Dr. James Hsieh witnessed the hopelessness metastatic cancer patients faced and decided to devote his life to the fight against cancer. His Ph.D. thesis concluded the mechanisms by which EBV EBNA2 hijacks Notch signaling for tumorigenesis and earned him the Young Investigator Award at Johns Hopkins Medical School in 1996. Dr. Hsieh entered Washington University for Internal Medicine and DFCI for Oncology training. Dr. Hsieh studied under the late Dr. Korsmeyer in 2000 as an HHMI Physician-Scientist Fellowship Awardee. He discovered proteolytic processing of MLL, purified the protease, and named it “Taspase1” in 2003. As NCI K01 Howard Temin Awardee, Dr. Hsieh joined the faculty at Wash U. in 2004. Dr. Hsieh was inducted into ASCI in 2010. As a physician scientist taking care of metastatic kidney cancer patients, Dr. Hsieh joined MSKCC to integrate his research and clinical interests in 2010, and founded the Translational Kidney Cancer Research Program (TKCRP) in 2011 to enable seamless collaboration among basic, preclinical, and clinical scientists. His team employs state-of-art platforms and clinical trial materials to integrate kidney cancer genomics, transcriptomics, proteomics, metabolomics, and therapeutics. His group pioneers a novel metabolic analytic algorithm (Metabologram) to interrogate human cancer metabolism in 2016. His laboratory recently established novel kidney cancer mouse models that recapitulate prevalent human kidney cancer mutations. Through studying kidney cancer, Dr. Hsieh proposed a novel cancer evolution (Braided Cancer River) model in 2015, capitalizing phenotypically, mechanistically convergent events to guide effective cancer therapy and overcome treatment-resistance. He was recruited back to Washington University in 2017. His primary translational goals are to develop novel mechanism-based, personalized therapeutics to prevent recurrence in high-risk patients and provide cure to significant number of metastatic kidney cancer patients.

Selected Publications:

1. Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, Heng DY, Larkin J and Ficarra V. Renal Cell Carcinoma. Nature Reviews Disease Primers. 2017. Mar 9;3:17009. doi: 10.1038/nrdp.2017.9. Review. PMID: 28276433

2. Jozefina Casuscelli, Nils Weinhold, Gunes Gundem, Lu Wang, Emily C. Zabor, Esther Drill, Wang PI, Nanjangud GJ, Almedina Redzematovic, Amrita M. Nargund, Brandon J. Manley, Maria E. Arcila, Nicholas M. Donin, John C. Cheville, R. Houston Thompson, Allan J. Pantuck, Paul Russo, Emily H. Cheng, William Lee, Satish K. Tickoo, Irina Ostrovnaya, Chad J. Creighton, Elli Papaemmanuil, Venkatraman E. Seshan, A. Ari Hakimi, Hsieh JJ. Genomic Landscape and Evolution of Metastatic Chromophobe Renal Cell Carcinoma. JCI Insight, 2017 Jun 15;2(12). pii:92688.doi:10.1172/jci.insight.92688. PMID: 28614790

3. Rileen Sinha, Andrew G. Winer, Michael Chevinsky, Christopher Jakubowski, Ying-Bei Chen, Yiyu Dong, Satish K. Tickoo, Victor E. Reuter, Paul Russo, Jonathan A. Coleman, Chris Sander, Hsieh JJ, A. Ari Hakimi. Evaluating renal cell carcinoma cell lines as tumor models. Nat Comm. 2017May 10;8:15165. doi: 10.1038/ncomms15165. PMID:28489074

4. Chung-Han Lee, Gunes Gundem, William Lee, Ying-Bei Chen, Justin R. Cross, Yiyu Dong, Almedina Redzematovic, Roy Mano, Elizabeth Y. Wei, Emily H. Cheng, Ramaprasad Srinivasan, Dayna Oschwald, A. Ari Hakimi, Mark P. Dunphy, W. Marston Linehan, Elli Papaemmanuil, & Hsieh JJ. Persistent Severe Hyperlactatemia and Metabolic Derangement in Lethal Succinate Dehydrogenase B Mutated Metastatic Kidney Cancer: Clinical Challenges and Examples of Extreme Warburg Effect. J Clin Oncol. Precision Oncology. 2017 DOI: 10.1200/PO.16.00007JCO Precision Oncology- published online May 4, 2017

5. Nargund AM, Pham C, Dong Y, Wang P.I., Osmanbeyoglu H.U., Xie Y, Aras O, Oyama T, Takeda S, Ray C.E., Dong Z, Berge M, Hakimi AA, Sebastien Monette S, Lekaye CL, Koutcher JA, Tickoo ST, Wang Z, Leslie CS, Weinhold N, Lee W, Cheng EC, Hsieh JJ. The SWI/SNF Protein PBRM1 Restrains VHL Loss-Driven Clear Cell Renal Cell Carcinoma. Cell Reports. 2017 Mar 21;18(12):2893-2906. doi: 10.1016/j.celrep.2017.02.074. PMID: 28329682

6. Hsieh JJ, David Chen, Patricia I. Wang, Mahtab Marker, Almedina Redzematovic, Ying-Bei Chen, S. Duygu Selcuklu, Nils Weinhold, Nancy Bouvier, Kety H. Huberman, Umesh Bhanot, Michael S. Chevinsky, Parul Patel, Patrizia Pinciroli, Helen H. Won, Daoqi You, Agnes Viale, William Lee, A. Ari Hakimi, Michael F. Berger, Nicholas D. Socci, Emily H. Cheng, Jennifer Knox, Martin H. Voss,Maurizio Voi, Robert J. Motzer. Efficacy Genomic Biomarkers of a Randomized Trial Comparing First-Line Everolimus and Sunitinib in Patients with Metastatic Renal Cell Carcinoma. Eur Urol, 2016 Oct 14 doi: 10.10.16/jeururo.2016.10.007

7. Chen Y, Xu J, Skanderup, AJ, Dong Y, Brannon AR, Wang L, Won WH, Wang PI, Nanjangud GJ, Jungbluth AA, Li W, Ojeda V, Hakimi AA, Voss MH, Schultz N, Motzer RJ, Russo P, Cheng EH, Giancotti FG, Lee W, Berger MF, Tickoo SK, Reuter VE, Hsieh JJ. Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets associated with varying clinical outcomes. Nat Comm. 2016 Oct 7 PMID: 2771345

8. Xu J, Pham CG, Albanese SK, Dong Y, Oyama T, Lee CH, Rodrik-Outmezguine V, Yao Z, Han S, Chen D, Parton DL, Chodera JD, Rosen N, Cheng EH, Hsieh JJ. Convergence and Cooperation of Mechanistically Distinct Cancer-Associated mTOR Activation Clusters. J Clin Invest. Mar 2;125(3):1203-14. PMID: 25664857; PMCID: PMC4362222.

9. Hakimi AA, Reznik E, Lee CH, Creighton CJ, Brannon AR, Luna A, Aksoy BA, Liu EM, Shen R, Lee W, Chen Y, Stirdivant SM, Russo P, Chen YB, Tickoo SK, Reuter VE, Cheng EH, Sander C, Hsieh JJ.An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma.Cancer Cell. 2016 Jan 11;29(1):104-16. doi: 10.1016/j.ccell.2015.12.004. PubMed PMID: 26766592.

10. Cancer Genome Atlas Research Network (Hsieh JJ) Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.N Engl J Med. 2016 Jan 14;374(2):135-45. doi: 10.1056/NEJMoa1505917. Epub 2015 Nov 4. PubMed PMID: 26536169.

Last Updated: 8/3/2017 11:20:24 AM

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