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院士风采
杰出青年
全所PI名录
 
 
地址:上海市岳阳路320号
邮编:200031
电话:86-21-54920000
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邮箱:sibcb@sibcb.ac.cn

全所PI名录 >

 
季红斌
研究员,研究组长,博士生导师
E-mail: hbji@@sibcb.ac.cn


个人简介

1991-1995年就读于吉林大学获学士学位,1995-2000年就读于中国科学院上海生化与细胞所获博士学位,2000-2007年在哈佛医学院从事博士后工作。2007年入选中科院“百人计划”,受聘于中科院上海生科院生化与细胞所,任研究员、博导。长期从事肺癌发病分子机理的研究,取得一系列原创性的科研成果。迄今为止发表论文130余篇,其中作为第一或通讯作者在Nature, Cancer Cell, Nature Genetics, Journal of Clinical Investigations, Journal of Clinical Oncology, PNAS 等期刊发表论文60余篇。荣获奖励包括上海市“浦江人才计划”, 中科院上海分院系统杰出青年科技创新人才, 国家杰出青年基金, 第七届上海青年科技英才, 上海市优秀学术带头人, 国家“万人计划”科技创新领军人才以及上海医学科技奖二等奖,上海市科技进步二等奖等。现任《中华肿瘤杂志》、Thoracic Cancer、《中国肺癌杂志》等期刊编委;中国抗癌协会上海市分子靶向治疗及免疫治疗委员会副主委,中国抗癌协会肿瘤转移专业委员会、中国抗癌协会肺癌专业委员会、中国医疗保健国际交流促进会胸部肿瘤分会委员。


研究方向

肺癌发病的分子机理


研究工作

        肺癌具有非常高的发病率和致死率,严重危害国民健康。深入理解肺癌发病的分子机理将为肺癌临床的精准治疗提供新的手段和策略。过去十几年来,我们围绕肺癌发病的过程,整合临床样本、动物模型以及肺癌细胞系的研究,系统性地揭示了肺癌发生发展甚至转移过程中的关键驱动基因及事件,取得一系列原创性的科研成果。特别是鉴定到RET融合是肺腺癌中新的驱动基因,目前RET融合已经在临床上作为分子靶标进行靶向治疗的应用,真正地实现科研成果的转化从而为肺癌患者带来福音。更为重要的是,开创性地利用肺癌动物模型证实肺腺鳞癌转分化的存在,在揭示其分子机制的基础上提出肺腺鳞癌转分化是肺癌耐药的新机制。 

        在这些前期工作基础上,课题组将继续围绕肺癌发病的分子机理开展以下三部分工作:
        1) 肺腺鳞癌转分化导致耐药的分子机制 我们将利用肺癌动物模型和类器官模型,结合单细胞测序、谱系示踪、三维基因组学、蛋白质组学等技术手段对肺腺鳞癌转分化的过程进行全面解析,以期全景式地描绘不同谱系来源的肺癌细胞相互转变及其命运决定的分子机制。同时结合大规模药物筛选平台,系统性地揭示肺腺癌和肺鳞癌对药物响应的特殊性,为肺腺鳞癌患者的临床治疗提供新的手段和策略。 
        2)小细胞肺癌化疗耐药的分子机制及克服策略 小细胞肺癌是所有肺癌病理亚型中分化程度最低、恶性程度最高的肿瘤。有意思的是,小细胞肺癌对化疗的响应非常好,导致化疗甚至替代手术成为小细胞肺癌患者治疗的首选方案。但是,小细胞肺癌患者也极易出现耐药,而且一旦发生耐药就面临几乎无药可救的困境,这种情况从上世纪七十年代开始一直持续至今。为了解决小细胞肺癌化疗耐药的问题,我们将通过建立患者来源的小细胞肺癌小鼠模型,模拟临床小细胞肺癌耐药的过程建立化疗耐药模型,并结合类器官模型的研究,系统性地揭示小细胞肺癌化疗耐药的分子进化机制,鉴定其中关键的靶分子,为克服小细胞肺癌的化疗耐药提供新思路和手段。 
        3)肺癌免疫微环境的解析及免疫治疗 免疫检查点PD1/PD-L1抗体治疗在肺癌临床治疗中取得了巨大成功。但是,只有20~30%的肺癌患者会对免疫检查点治疗有显著的反应。为了让更多的肺癌患者从免疫治疗中获益,我们认为需要对肺癌免疫微环境进行更加深入的理解。我们将利用临床肺癌样本系统性地分析其免疫微环境中各种细胞的组成和潜在的功能,尤其关注调节性T细胞的功能及其潜在的标记物,并基于此筛选特异性的抗体开展免疫微环境细胞的靶向治疗研究,为临床肺癌的免疫治疗尤其是免疫联合治疗提供新的思路。


代表性论文

  1. Yao S, Huang H, Han X, Ye Y, Qin Z, Zhao G, Li F, Hu G, Hu L*, Ji H*. (2019). Keratin 14-high subpopulation mediates lung cancer metastasis potentially through Gkn1 upregulation. Oncogene 2019 Jul 18. doi: 10.1038/s41388-019-0889-0. [Epub ahead of print]
  2. Wang Y, Zhang J, Ren S, Sun D, Huang HY, Wang H, Jin Y, Li F, Zheng C, Yang L, Deng L, Jiang Z, Jiang T, Han X, Hou S, Guo C, Li F, Gao D, Qin J, Gao D, Chen L, Lin SH, Wong KK, Li C*, Hu L*, Zhou C*, Ji H*. Branched-Chain Amino Acid Metabolic Reprogramming Orchestrates Drug Resistance to EGFR Tyrosine Kinase Inhibitors. Cell Reports 2019;28(2):512-525.e6.
  3. Gao L, Hu Y, Tian Y, Fan Z, Wang K, Li H, Zhou Q, Zeng G, Hu X, Yu L, Zhou S, Tong X, Huang H, Chen H, Liu Q, Liu W, Zhang G, Zeng M, Zhou G, He Q, Ji H*, Chen L*. Lung cancer deficient in the tumor suppressor GATA4 is sensitive to TGFBR1 inhibition. Nat Commun 2019;10(1):1665.
  4. Liu Q, Liu K, Cui G, Huang X, Yao S, Guo W, Qin Z, Li Y, Yang R, Pu W, Zhang L, He L, Zhao H, Yu W, Tang M, Tian X, Cai D, Nie Y, Hu S, Ren T, Qiao Z, Huang H, Zeng YA, Jing N, Peng G, Ji H*, Zhou B*. Lung regeneration by multipotent stem cells residing at the bronchioalveolar-duct junction. Nat Genet 2019;51(4):728-738.
  5. Zhao G, Gong L, Su D, Jin Y, Guo C, Yue M, Yao S, Qin Z, Ye Y, Tang Y, Wu Q, Zhang J, Cui B, Ding Q, Huang H, Hu L, Chen Y, Zhang P, Hu G, Chen L, Wong KK, Gao D*, Ji H*. Cullin5 deficiency promotes small-cell lung cancer metastasis by stabilizing integrin β1. J Clin Invest 2019;129(3):972-987.
  6. Y. Wang, T. Jiang, Z. Qin, J. Jiang, Q. Wang, S. Yang, C. Rivard, G. Gao, T. L. Ng, M.M. Tu, H. Yu, H. Ji*, C. Zhou*, S. Ren*, J. Zhang, P. Bunn, R. C. Doebele, D. R. Camidge, F. R. Hirsch. HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib. Annals of Oncology 2019 Mar 1;30(3):447-455.
  7. Wu Q, Tian Y, Zhang J, Tong X, Huang H, Li S, Zhao H, Tang Y, Yuan C, Wang K, Fang Z, Gao L, Hu X, Li F, Qin Z, Yao S, Chen T, Chen H, Zhang G, Liu W, Sun Y, Chen L, Wong KK, Ge K, Chen L*, Ji H*. In vivo CRISPR screening unveils histone demethylase UTX as an important epigenetic regulator in lung tumorigenesis. Proc Natl Acad Sci U S A 2018;115(17):E3978-E3986.
  8. Huang H, Zhang W, Pan Y, Gao Y, Deng L, Li F, Li F, Ma X, Hou S, Xu J, Li P, Li X, Hu G, Li C, Chen H, Zhang L, Ji H*. YAP Suppresses Lung Squamous Cell Carcinoma Progression via Deregulation of the DNp63-GPX2 Axis and ROS Accumulation. Cancer Res 2017;77(21):5769-5781.
  9. Hou S, Han X, Ji H*. Squamous Transition of Lung Adenocarcinoma and Drug Resistance. Trends in Cancer 2016;2(9):463-466.
  10. Hou S, Zhou S, Qin Z, Yang L, Han X, Yao S, Ji H*. Evidence, Mechanism, and Clinical Relevance of the Transdifferentiation from Lung Adenocarcinoma to Squamous Cell Carcinoma. Am J Pathol 2017;187(5):954-962.
  11. Li F, Fang Z, Zhang J, Li C, Liu H, Xia J, Zhu H, Guo C, Qin Z, Li F, Han X, Wang Y, Feng Y, Wang Y, Zhang W, Wang Z, Jin Y, Sun Y, Wei W, Zeng R, Chen H, Ji H*. Identification of TRA2B-DNAH5 fusion as a novel oncogenic driver in human lung squamous cell carcinoma. Cell Res 2016;26(10):1149-1164.
  12. Zhang W, Gao Y, Li F, Tong X, Ren Y, Han X, Yao S, Long F, Yang Z, Fan H, Zhang L*, Ji H*. YAP promotes malignant progression of Lkb1-deficient lung adenocarcinoma through downstream regulation of survivin. Cancer Res 2015;75(21):4450-4457.
  13. Li F, Han X, Li F, Wang R, Wang H, Gao Y, Wang X, Fang Z, Zhang W, Yao S, Tong X, Wang Y, Feng Y, Sun Y, Li Y, Wong KK, Zhai Q, Chen H*, Ji H*. LKB1 Inactivation Elicits a Redox Imbalance to Modulate Non-small Cell Lung Cancer Plasticity and Therapeutic Response. Cancer Cell 2015;27(5):698-711.
  14. Gao Y, Zhang W, Han X, Li F, Wang X, Wang R, Fang Z, Tong X, Yao S, Li F, Feng Y, Sun Y, Hou Y, Yang Z, Guan K, Chen H, Zhang L*, Ji H*. YAP inhibits squamous transdifferentiation of Lkb1-deficient lung adenocarcinoma through ZEB2-dependent DNp63 repression. Nat Commun 2014;5:4629.
  15. Wang Y, Gao J, Guo X, Tong T, Shi X, Li L, Qi M, Wang Y, Cai M, Jiang J, Xu C*, Ji H*, Wang H*. Regulation of EGFR nanocluster formation by ionic protein-lipid interaction. Cell Res 2014;24(8):959-976.
  16. Wang R, Wang L, Li Y, Hu H, Shen L, Shen X, Pan Y, Ye T, Zhang Y, Luo X, Zhang Y, Pan B, Li B, Li H, Zhang J, Pao W, Ji H*, Sun Y*, Chen H*. FGFR1/3 Tyrosine Kinase Fusions Define a Unique Molecular Subtype of Non-Small Cell Lung Cancer. Clin Cancer Res 2014;20(15):4107-4114. 
  17. Han X, Li F, Fang Z, Gao Y, Li F, Fang R, Yao S, Sun Y, Li L, Zhang W, Ma H, Xiao Q, Ge G, Fang J, Wang H, Zhang L, Wong KK, Chen H, Hou Y, Ji H*. Transdifferentiation of Lung Adenocarcinoma in mice with Lkb1 Deficiency to Squamous Cell Carcinoma. Nat Commun 2014;5:3261.
  18. Jiao S, Wang H, Shi Z, Dong A, Zhang W, Song X, He F, Wang Y, Zhang Z, Wang W, Wang X, Guo T, Li P, Zhao Y, Ji H*, Zhang L*, Zhou Z*. A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer. Cancer Cell 2014;25:166-180.
  19. Fang R, Zheng C, Sun Y, Han X, Gao B, Li C, Liu H, Wong KK, Liu XY*, Chen H*, Ji H*. Brief Report: Integrative genomic analysis reveals a high frequency of LKB1 genetic alteration in Chinese lung adenocarcinomas. J Thorac Oncol 2014;9(2):254-258.
  20. Zhang W, Gao Y, Li P, Shi Z, Guo T, Li F, Han X, Feng Y, Zheng C, Wang Z, Li F, Chen H, Zhou Z*, Zhang L*, Ji H*. VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex. Cell Res 2014;24(3):331-343.
  21. Wang R, Hu H, Pan Y, Li Y, Ye T, Li C, Luo X, Wang L, Li H, Zhang Y, Li F, Lu Y, Lu Q, Xu J, Garfield D, Shen L, Ji H#, Pao W, Sun Y#, Chen H#,*. RET Fusions Define a Unique Molecular and Clinicopathologic Subtype of Non-Small-Cell Lung Cancer. J Clin Oncol 2012, 30(35):4352-4359.
  22. Feng Y, Wang Y, Wang Z, Fang Z, Li F, Gao Y, Liu H, Xiao T, Li F, Zhou Y, Zhai Q, Liu X, Sun Y, Bardeesy N, Wong KK, Chen H, Xiong ZQ, Ji H*. The CRTC1-NEDD9 signaling axis mediates lung cancer progression caused by LKB1 loss. Cancer Res 2012;72(24):6502-6511.
  23. Fang R, Xiao T, Fang Z, Sun Y, Li F, Gao Y, Feng Y, Li L, Wang Y, Liu X, Chen H, Liu XY*, Ji H*. MicroRNA-143 (miR-143) regulates cancer glycolysis via targeting hexokinase 2 gene. J Biol Chem 2012;287(27):23227–23235. 
  24. Li F, Feng Y, Fang R, Fang Z, Xia J, Han X, Chen H*, Liu H*, Ji H*. Identification of RET gene fusion by exon array analyses in "pan-negative" lung cancer from never smokers. Cell Res 2012;22(5):928-931.
  25. Li C, Sun Y, Fang R, Han X, Luo X, Wang R, Pan Y, Hu H, Zhang Y, Pao W, Shen L, Ji H*, Chen H*. Lung Adenocarcinomas with HER2-Activating Mutations Are Associated with Distinct Clinical Features and HER2/EGFR Copy Number Gains. J Thorac Oncol 2012;7(1):85-89.
  26. Fang Z, Tian W*, Ji H*. A network-based gene-weighting approach for pathway analysis. Cell Res 2012;22(3):565-580.
  27. Li C, Sun Y, Fang Z, Han X, Fang R, Zhang Y, Pan Y, Zhang W, Ren Y, Ji H*, Chen H*. Comprehensive Analysis of Epidermal Growth Factor Receptor (EGFR) Gene Status in Lung Adenocarcinoma from Chinese Patients. J Thorac Oncol 2011;6:1016-1021.
  28. Gao Y, Xiao Q, Ma H, Li L, Liu J, Feng Y, Fang Z, Wu J, Han X, Zhang J, Sun Y, Wu G, Padera R, Chen H, Wong KK, Ge G*, Ji H*. LKB1 inhibits lung cancer progression through lysyl oxidase and extracellular matrix remodeling. Proc Natl Acad Sci U S A 2010;107(44):18892-18897. 
  29. Sun Y, Ren Y, Fang Z, Li C, Fang R, Gao B, Han X, Tian W, Pao W#, Chen H#,*, Ji H#. Lung adenocarcinoma from East asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases. J Clin Oncol 2010;28, 4616-20.
  30. Gao B, Sun Y, Zhang J, Ren Y, Fang R, Han X, Liu XY, Pao W, Chen H*, Ji H*. Spectrum of LKB1, EGFR and KRAS mutations in Chinese lung adenocarcinomas. J Thorac Oncol 2010; 5:1130-1135. 
  31. Wang L, Xiong Y, Sun Y, Fang Z, Li L, Ji H*, Shi T*. HLungDB: an integrated database of human lung cancer research. Nucleic Acids Res 2010;38:D665-669. 
  32. Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K, Kozlowski P, Torrice C, Wu MC, Shimamura T, Perera SA, Liang MC, Cai D, Naumov GN, Bao L, Contreras CM, Li D, Chen L, Krishnamurthy J, Koivunen J, Chirieac LR, Padera RF, Bronson RT, Lindeman NI, Christiani DC, Lin X, Shapiro GI, Janne PA, Johnson BE, Meyerson M, Kwiatkowski DJ, Castrillon DH, Bardeesy N, Sharpless NE, Wong KK. LKB1 modulates lung cancer differentiation and metastasis. Nature 2007;448(7155):807-810. 
  33. Li D#, Shimamura T#, Ji H#, Chen L, Haringsma HJ, McNamara K, Liang MC, Perera SA, Zaghlul S, Borgman CL, Kubo S, Takahashi M, Sun Y, Chirieac LR, Padera RF, Lindeman NI, Janne PA, Thomas RK, Meyerson ML, Eck MJ, Engelman JA, Shapiro GI, Wong KK. Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy. Cancer Cell 2007;12(1):81-93.
  34. Ji H, Wang Z, Perera SA, Li D, Liang MC, Zaghlul S, McNamara K, Chen L, Albert M, Sun Y, Al-Hashem R, Chirieac LR, Padera R, Bronson RT, Thomas RK, Garraway LA, Jänne PA, Johnson BE, Chin L, Wong KK. Mutations in BRAF and KRAS Converge on Activation of the Mitogen-Activated Protein Kinase Pathway in Lung Cancer Mouse Models. Cancer Res 2007;67(10):4933-4939.
  35. Li D#, Ji H#,Zaghlul S, McNamara K, Liang MC, Shimamura T, Kubo S, Takahashi M, Chirieac LR, Padera RF, Scott AM, Jungbluth AA, Cavenee WK, Old LJ, Demetri GD, Wong KK. Therapeutic anti-EGFR antibody 806 generates responses in murine de novo EGFR mutant-dependent lung carcinomas. J Clin Invest 2007;117(2):346-352.
  36. Shimamura T#, Ji H#, Minami Y, Thomas RK, Lowell AM, Shah K, Greulich H, Glatt KA, Meyerson M, Shapiro GI, Wong KK. Non-small cell lung cancer and Ba/F3 transformed cells harboring the ERBB2 G776insV_G/C mutation are sensitive to the dual-specific EGFR and ERBB2 inhibitor HKI-272. Cancer Res 2006;66(13):6487-6491.
  37. Ji H, Li D, Chen L, Shimamura T, Kobayashi S, McNamara K, Mahmood U, Mitchell A, Sun Y, Al-Hashem R, Chirieac LR, Padera R, Bronson R. T, Kim W, Jänne PA, Shapiro GI, Tenen D, Johnson BE, Weissleder R, Sharpless NE, Wong KK. The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR targeted therapies. Cancer Cell 2006;9(6):485-495.
  38. Ji H, Zhao X, Yuza Y, Shimamura T, Li D, Protopopov A, Jung BL, McNamara K, Xia H, Glatt KA, Thomas RK, Sasaki H, Horner JW, Eck M, Mitchell A, Sun Y, Al-Hashem R, Bronson RT, Rabindran SK, Discafani CM, Maher E, Shapiro GI, Meyerson M, Wong KK. Epidermal Growth Factor Receptor Variant III Mutations in Lung Tumorigenesis and Sensitivity to Tyrosine Kinase Inhibitors. Proc Natl Acad Sci USA 2006;103(20):7817-7822.
  39. Ji H, Houghton AM, Mariani TJ, Perera S, Kim CB, Padera R, Tonon G, McNamara K, Marconcini LA, Hezel A, El-Bardeesy N, Bronson RT, Sugarbaker D, Shapiro SD, Wong KK. K-Ras Activation Generates An Inflammatory Response in Lung Tumors. Oncogene 2006;25(14):2105-2112. 
  40. Abadía-Molina AC#, Ji H#, Faubion WA, Julien A, Latchman Y, Yagita H, Sharpe A, Bhan AK, Terhorst C. CD48 controls T-cell and antigen-presenting cell functions in experimental colitis. Gastroenterology 2006;130(2):424-434.
  41. Ji HB, Liao G, Faubion WA, Abadia-Molina AC, Cozzo C, Laroux FS, Caton A, Terhorst C. Cutting edge: the natural ligand for glucocorticoid-induced TNF receptor-related protein abrogates regulatory T cell suppression. J Immunol 2004;172(10): 5823-5827.
  42. Ji HB, Gupta A, Okamoto S, Blum MD, Tan L, Goldring MB, Lacy E, Roy AL, Terhorst C. T cell-specific expression of the murine CD3delta promoter. J Biol Chem 2002;277(49): 47898-47906.

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