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170余篇，被引18000余次，其中作为第一或通讯作者在Nature, Cancer Cell, Nature Cancer, Nature Genetics, Journal of Clinical Investigations, Journal of Clinical Oncology, PNAS 等期刊发表论文80余篇。荣获奖励包括国家杰出青年基金,上海市优秀学术带头人, 上海医学科技奖二等奖, 上海市科技进步二等奖等。任 PLoS Genetics, Journal of Genetics and Genomics 副主编，British Journal of Cancer、Thoracic Cancer、《中华肿瘤杂志》、《中国肺癌杂志》等编委，上海市医学会肿瘤靶分子专业委员会副主委，上海市分子靶向治疗及免疫治疗专业委员副主委，中国抗癌协会肺癌专业委员会及肿瘤转移专业委员会委员，中国医疗保健国际交流促进会胸部肿瘤分会委员。

　　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。

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22. Zhang Z, Dong C, Yu G, Cheng W, Liang Y, Pan Y, Li H, Ji H*. Smart and dual-targeted BSA nanomedicine with controllable release by high autolysosome levels. Colloids Surf B Biointerfaces. 2019 Oct 1;182:110325.
23. 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 Rep. 2019 Jul 9;28(2):512-525.e6.
24. Jin Y, Ma D, Gramyk T, Guo C, Fang R, Ji H*, Shi YG*. Kdm1a promotes SCLC progression by transcriptionally silencing the tumor suppressor Rest. Biochem Biophys Res Commun. 2019 May 27. pii: S0006-291X(19)31004-6.
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26. 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 Apr;51(4):728-738.
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47. 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.
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49. 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 Feb;9(2):254-8.
50. 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 Mar;24(3):331-43. 
51. Jin Y, Li F, Zheng C, Wang Y, Fang Z, Guo C, Wang X, Liu H, Deng L, Li C, Wang H, Chen H, Feng Y*, Ji H*. NEDD9 promotes lung cancer metastasis through epithelial-mesenchymal transition. Int J Cancer. 2014 May 15;134(10):2294-304.  
52. Wang Z, Sun Y, Gao B, Lu Y, Fang R, Gao Y, Xiao T, Liu XY, Pao W, Zhao Y*, Chen H*, Ji H*. Two co-existing germline mutations P53 V157D and PMS2 R20Q promote tumorigenesis in a familial cancer syndrome. Cancer Lett. 2014 Jan 1;342(1):36-42.
53. Zhang Y, Sun Y, Li Y, Fang Z, Wang R, Pan Y, Hu H, Luo X, Ye T, Li H, Wang L, Chen H*, Ji H*. ANCCA Protein Expression is a Novel Independent Poor Prognostic Marker in Surgically Resected Lung Adenocarcinoma. Ann Surg Oncol. 2013 Dec;20 Suppl 3:S577-82.
54. Han C, Huang Z, Zheng C, Wan L, Lai Y, Peng S, Ding K*, Ji H*, Zhang Y*. Nitric oxide donating anilinopyrimidines: Synthesis and biological evaluation as EGFR inhibitors. Eur J Med Chem. 2013 Aug;66:82-90.
55. Han C, Huang Z, Zheng C, Wan L, Zhang L, Peng S, Ding K, Ji H*, Tian J*, Zhang Y*. Novel Hybrids of (Phenylsulfonyl)furoxan and Anilinopyrimidine as Potent and Selective Epidermal Growth Factor Receptor Inhibitors for Intervention of Non-Small-Cell Lung Cancer.J Med Chem. 2013 Jun 13;56(11):4738-48.
56. 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):4352-9. 
57. 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):6502-11.
58. Huang H, Xiao T, He L, Ji H*, Liu XY*. Interferon-β-armed oncolytic adenovirus induces both apoptosis and necroptosis in cancer cells. Acta Biochim Biophys Sin (Shanghai). 2012, 44(9):737-45.
59. Wang Z, Feng Y, Bardessy N, Wong KK, Liu XY*, Ji H*. Temporal Dissection of K-rasG12D Mutant In Vitro and In Vivo Using a Regulatable K-rasG12D Mouse Allele. PLoS One. 2012; 7(5): e37308. 
60. 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*. miR-143 regulates cancer glycolysis via targeting hexokinase 2. J Biol Chem. 2012, 287(27):23227–35. 
61. 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):928-31.
62. Xao T, Bao L, Ji H*. Finding biomarkers for non-small cell lung cancer diagnosis and prognosis. Front. Biol. 2012, 7(1): 14–23.
63. 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):85-9.
64. Fang Z, Tian W*, Ji H*.  A network-based gene-weighting approach for pathway analysis. Cell Res. 2012, 22(3):565-80.
65. Li C, Fang R, Sun Y, Han X, Li F, Gao B, Iafrate AJ, Liu XY, Pao W, Chen H, Ji H*. Spectrum of oncogenic driver mutations in lung adenocarcinomas from East asian never smokers. PLoS One. 2011, 6(11):e28204.
66. 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, 6:1016-21.
67. Gao Y, Ge G*, Ji H*. LKB1 in lung cancerigenesis: a serine/threonine kinase as tumor suppressor. Protein Cell. 2011, 2(2):99-107.
68. Zheng C, Sun Y, Ye X, Chen HQ*, Ji HB*. Establishment and characterization of primary Chinese lung cancer cell lines. Acta Pharmacol Sin. 2011, 32, 385-92.
69. 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):18892-7. 
70. 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.
71. 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, 1130-5. 
72. Sun Y, Fang R, Gao B, Han X, Zhang J, Pao W, Chen H, Ji H*. Comparable rate of EGFR kinase domain mutation in lung adenocarcinomas from Chinese male and female never-smokers. Acta Pharmacol Sin. 2010, 31, 647-8.
73. Ji H*. Mechanistic insights into acquired drug resistance in EGFR mutation targeted lung cancer therapy. Can Sci. 2010,101(9):1933-8. 
74. 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, D665-9. 
75. 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):807-10. 
76. 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.
77. Ji H, Wang Z, Perera A.S., Li D, Liang M-C, Zaghlul S, McNamara K, Chen L, Albert M, Sun Y, Al-Hashem R, Chirieac L.R., Padera R., Bronson R.T., Thomas R. K., Garraway L.A., Janne P.A., Johnson B.E., Chin L., and 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):4933-9.
78. 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):346-52.
79. Ji H, Sharpless NE, Wong KK. EGFR targeted therapy: view from biological standpoint. Cell Cycle. 2006, 5(18):2072-6.
80. Shimamura T^#, Ji H^#，Minami Y, Thomas R.K., Lowell A.M., Shah K., Greulich H, Glatt K.A., Meyerson M.L., Shapiro G.I. and 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):6487-91. 
81. Ji H, Li D, Chen L, Shimamura T, Kobayashi S, McNamara K, Mahmood U, Mitchell A, Sun Y, Al-Hashem R, Chirieac L.R, Padera R, Bronson R. T, Kim W, Janne P.A, Shapiro G.I, Tenen D, Johnson B.E, Weissleder R, Sharpless N.E, 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):485-95.
82. Ji H, Zhao X, Yuza Y, Shimamura T, Li D, Protopopov A, Jung B.L, McNamara K, Xia H, Glatt K.A, Thomas R.K, Sasaki H, Horner J.W, Mitchell A, Sun Y, Al-Hashem R,  Bronson R.T, Rabindran S.K, Discafani C.M, Maher E, Shapiro G.I, 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):7817-22.
83. 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):2105-12. 
84. Abadía-Molina AC^#, Ji HB^#，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):424-34. 
85. 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): 5823-7.
86. 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): 47898-906.

 

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