Research Summary

Our lab studies molecular genetics and signaling pathways during liver cancer development. Our research focuses on primary liver cancers, including hepatocellular carcinoma, intrahepatic cholangiocarcinoma and hepatoblastoma. We are studying the biochemical and metabolic crosstalk among pathways deregulated in primary liver cancers, such as HIPPO, NOTCH, AKT/mTOR and c-MYC cascades. We are testing novel, targeted therapies for liver cancer treatment using drugs that specifically target these pathways.

Research Funding

  • March 1, 2020 - February 28, 2025 - Signaling pathways during hepatocarcinogenesis, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA239251
  • June 19, 2018 - May 31, 2023 - Role of Cancer-Associated Fibroblasts in Cholangiocarcinoma, Co-Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA228483
  • April 1, 2020 - March 31, 2022 - Cabozentinib based combination therapy for the treatment of hepatocellular carcinoma, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R03CA249236
  • April 5, 2016 - March 31, 2021 - Signaling cascades in cholangiocarcinoma development, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA190606

Education

Beijing Medical University, Beijing China, Bachelor of Medicine, 1992, Medicine
Harvard University, Ph.D., 1997, Cell and Developmental Biology

Honors & Awards

  • 1991-1992
    First Prize Award, Beijing Medical University, Beijing, China
  • 1998-2001
    Postdoctoral Fellowship Award, Life Science Research Foundation, Baltimore, MD

Selected Publications

  1. Méndez-Lucas A, Lin W, Driscoll PC, Legrave N, Novellasdemunt L, Xie C, Charles M, Wilson Z, Jones NP, Rayport S, Rodríguez-Justo M, Li V, MacRae JI, Hay N, Chen X, Yuneva M. Identifying strategies to target the metabolic flexibility of tumours. Nat Metab. 2020 04; 2(4):335-350.  View on PubMed
  2. Zhou Y, Xu M, Liu P, Liang B, Qian M, Wang H, Song X, Nyshadham P, Che L, Calvisi DF, Li F, Lin S, Chen X. Mammalian Target of Rapamycin Complex 2 Signaling Is Required for Liver Regeneration in a Cholestatic Liver Injury Murine Model. Am J Pathol. 2020 07; 190(7):1414-1426.  View on PubMed
  3. Chen B, Garmire L, Calvisi DF, Chua MS, Kelley RK, Chen X. Publisher Correction: Harnessing big 'omics' data and AI for drug discovery in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2020 Mar 11.  View on PubMed
  4. Wang P, Song X, Cao D, Cui K, Wang J, Utpatel K, Shang R, Wang H, Che L, Evert M, Zhao K, Calvisi DF, Chen X. Oncogene-dependent function of BRG1 in hepatocarcinogenesis. Cell Death Dis. 2020 02 04; 11(2):91.  View on PubMed
  5. Xu M, Wang J, Xu Z, Li R, Wang P, Shang R, Cigliano A, Ribback S, Solinas A, Pes GM, Evert K, Wang H, Song X, Zhang S, Che L, Pascale RM, Calvisi DF, Liu Q, Chen X. SNAI1 Promotes the Cholangiocellular Phenotype, but not Epithelial-Mesenchymal Transition, in a Murine Hepatocellular Carcinoma Model. Cancer Res. 2019 11 01; 79(21):5563-5574.  View on PubMed
  6. Xu Z, Xu M, Liu P, Zhang S, Shang R, Qiao Y, Che L, Ribback S, Cigliano A, Evert K, Pascale RM, Dombrowski F, Evert M, Chen X, Calvisi DF, Chen X. The mTORC2-Akt1 Cascade Is Crucial for c-Myc to Promote Hepatocarcinogenesis in Mice and Humans. Hepatology. 2019 11; 70(5):1600-1613.  View on PubMed
  7. Wang J, Wang H, Peters M, Ding N, Ribback S, Utpatel K, Cigliano A, Dombrowski F, Xu M, Chen X, Song X, Che L, Evert M, Cossu A, Gordan J, Zeng Y, Chen X, Calvisi DF. Loss of Fbxw7 synergizes with activated Akt signaling to promote c-Myc dependent cholangiocarcinogenesis. J Hepatol. 2019 10; 71(4):742-752.  View on PubMed
  8. Qiao Y, Wang J, Karagoz E, Liang B, Song X, Shang R, Evert K, Xu M, Che L, Evert M, Calvisi DF, Tao J, Wang B, Monga SP, Chen X. Axis inhibition protein 1 (Axin1) Deletion-Induced Hepatocarcinogenesis Requires Intact β-Catenin but Not Notch Cascade in Mice. Hepatology. 2019 12; 70(6):2003-2017.  View on PubMed
  9. Che L, Chi W, Qiao Y, Zhang J, Song X, Liu Y, Li L, Jia J, Pilo MG, Wang J, Cigliano A, Ma Z, Kuang W, Tang Z, Zhang Z, Shui G, Ribback S, Dombrowski F, Evert M, Pascale RM, Cossu C, Pes GM, Osborne TF, Calvisi DF, Chen X, Chen L. Cholesterol biosynthesis supports the growth of hepatocarcinoma lesions depleted of fatty acid synthase in mice and humans. Gut. 2020 01; 69(1):177-186.  View on PubMed
  10. Wang J, Dong M, Xu Z, Song X, Zhang S, Qiao Y, Che L, Gordan J, Hu K, Liu Y, Calvisi DF, Chen X. Notch2 controls hepatocyte-derived cholangiocarcinoma formation in mice. Oncogene. 2018 06; 37(24):3229-3242.  View on PubMed
  11. Zhang S, Wang J, Wang H, Fan L, Fan B, Zeng B, Tao J, Li X, Che L, Cigliano A, Ribback S, Dombrowski F, Chen B, Cong W, Wei L, Calvisi DF, Chen X. Hippo Cascade Controls Lineage Commitment of Liver Tumors in Mice and Humans. Am J Pathol. 2018 04; 188(4):995-1006.  View on PubMed
  12. Dong M, Liu X, Evert K, Utpatel K, Peters M, Zhang S, Xu Z, Che L, Cigliano A, Ribback S, Dombrowski F, Cossu A, Gordan J, Calvisi DF, Evert M, Liu Y, Chen X. Efficacy of MEK inhibition in a K-Ras-driven cholangiocarcinoma preclinical model. Cell Death Dis. 2018 01 18; 9(2):31.  View on PubMed
  13. Xu Z, Hu J, Cao H, Pilo MG, Cigliano A, Shao Z, Xu M, Ribback S, Dombrowski F, Calvisi DF, Chen X. Loss of Pten synergizes with c-Met to promote hepatocellular carcinoma development via mTORC2 pathway. Exp Mol Med. 2018 01 05; 50(1):e417.  View on PubMed
  14. Zhang S, Song X, Cao D, Xu Z, Fan B, Che L, Hu J, Chen B, Dong M, Pilo MG, Cigliano A, Evert K, Ribback S, Dombrowski F, Pascale RM, Cossu A, Vidili G, Porcu A, Simile MM, Pes GM, Giannelli G, Gordan J, Wei L, Evert M, Cong W, Calvisi DF, Chen X. Pan-mTOR inhibitor MLN0128 is effective against intrahepatic cholangiocarcinoma in mice. J Hepatol. 2017 12; 67(6):1194-1203.  View on PubMed
  15. Méndez-Lucas A, Li X, Hu J, Che L, Song X, Jia J, Wang J, Xie C, Driscoll PC, Tschaharganeh DF, Calvisi DF, Yuneva M, Chen X. Glucose Catabolism in Liver Tumors Induced by c-MYC Can Be Sustained by Various PKM1/PKM2 Ratios and Pyruvate Kinase Activities. Cancer Res. 2017 08 15; 77(16):4355-4364.  View on PubMed
  16. Liu P, Ge M, Hu J, Li X, Che L, Sun K, Cheng L, Huang Y, Pilo MG, Cigliano A, Pes GM, Pascale RM, Brozzetti S, Vidili G, Porcu A, Cossu A, Palmieri G, Sini MC, Ribback S, Dombrowski F, Tao J, Calvisi DF, Chen L, Chen X. A functional mammalian target of rapamycin complex 1 signaling is indispensable for c-Myc-driven hepatocarcinogenesis. Hepatology. 2017 07; 66(1):167-181.  View on PubMed
  17. Cao D, Song X, Che L, Li X, Pilo MG, Vidili G, Porcu A, Solinas A, Cigliano A, Pes GM, Ribback S, Dombrowski F, Chen X, Li L, Calvisi DF. Both de novo synthetized and exogenous fatty acids support the growth of hepatocellular carcinoma cells. Liver Int. 2017 01; 37(1):80-89.  View on PubMed
  18. Li L, Che L, Tharp KM, Park HM, Pilo MG, Cao D, Cigliano A, Latte G, Xu Z, Ribback S, Dombrowski F, Evert M, Gores GJ, Stahl A, Calvisi DF, Chen X. Differential requirement for de novo lipogenesis in cholangiocarcinoma and hepatocellular carcinoma of mice and humans. Hepatology. 2016 06; 63(6):1900-13.  View on PubMed
  19. Hu J, Che L, Li L, Pilo MG, Cigliano A, Ribback S, Li X, Latte G, Mela M, Evert M, Dombrowski F, Zheng G, Chen X, Calvisi DF. Co-activation of AKT and c-Met triggers rapid hepatocellular carcinoma development via the mTORC1/FASN pathway in mice. Sci Rep. 2016 Feb 09; 6:20484.  View on PubMed
  20. Li L, Pilo GM, Li X, Cigliano A, Latte G, Che L, Joseph C, Mela M, Wang C, Jiang L, Ribback S, Simile MM, Pascale RM, Dombrowski F, Evert M, Semenkovich CF, Chen X, Calvisi DF. Inactivation of fatty acid synthase impairs hepatocarcinogenesis driven by AKT in mice and humans. J Hepatol. 2016 Feb; 64(2):333-341.  View on PubMed

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