联系方式

实验室位置:

武汉大学基础医学院3号楼5楼

Email:

kegong@whu.edu.cn

龚克 特聘研究员

职称职务:特聘研究员

学科专业:免疫学

研究方向:肿瘤信号通路与靶向和免疫治疗抵抗的分子机制,数据库和精准治疗

实验室位置:武汉大学基础医学院3号楼5楼

Email: kegong@whu.edu.cn

学习经历

2003-2007 武汉大学生命科学学院,生物学,学士

2008-2014 武汉大学生命科学学院,细胞生物学,博士

主要工作经历与任职

2014-2015 美国埃默里大学 博士后

2015-2019 美国德州大学西南医学中心 博士后

2019-2021 美国德州大学西南医学中心 讲师

2021-至今 武汉大学基础医学院免疫学系 特聘研究员

目前主要科学研究领域和兴趣

以表皮生长因子EGFR为代表的受体酪氨酸激酶(RTK)癌基因信号异常与肿瘤发生发展及治疗抵抗高度相关。当前肿瘤精准治疗正面临两大挑战:(1)靶向治疗药物虽然对癌基因异常肿瘤早期效果显著,但最终仍不可避免发生获得性耐药,并且野生型原发性耐药;(2)免疫检查点药物虽能持续抑制部分病人的肿瘤,但适应症标志物不能确定,且往往对适用靶向治疗的如RTK异常肿瘤疗效欠佳。

前期在美国的课题组研究发现,引发炎症反应并杀死肿瘤的肿瘤坏死因子TNF也能促进非小细胞肺癌和脑神经胶质瘤的耐药生存(Gong et al. Journal of Clinical Investigation 2018,Guo et al. Nature Neuroscience 2017,Guo et al. Neuro-Oncology 2019,Gong et al. Neoplasia 2021),此外,促肿瘤免疫的天然免疫通路相关的I型干扰素基因,在肿瘤靶向治疗中却扮演着诱导治疗抵抗的角色并影响PDL1相关的免疫治疗(Gong et al. Nature Cancer 2020)。更为重要的是,一种临床常用且强效的免疫抑制剂和消炎药——糖皮质激素——被发现具有广谱且强力的耐药通路阻断效果(Gong et al. Nature Communications, 2021),目前正在美国德州大学西南医学中心开展II期临床试验:NCT04497584。利用算法模型进行大数据分析,提示EGFR配体依赖的过度功能活化可将EGFR受体功能从促进肿瘤生长为主(grow)转变为抑制肿瘤侵袭优先(go),经美国课题组的实验验证,发现了脑神经胶质瘤对靶向EGFR治疗原发性耐药的分子机制(Nature Cell Biology,2022),揭示了胶质瘤EGFR-TKI临床失败的潜在原因,一项临床联合治疗方案即将推进转化。

课题组研究方向包括:1.免疫应答与炎症反应、代谢产物、酪氨酸激酶等信号通路参与肿瘤靶向与免疫治疗抵抗的分子机制;2.围绕临床医学实践问题,对作用于肿瘤发生发展及治疗耐药,并影响病人药物敏感性、预后转归的新基因、新通路,开展数据库筛查、实验模型验证、及分子机制探索等基础医学和生命科学研究;3.针对新靶点和耐药机制的临床新药物新方案的发现与临床及产业成果转化;4.建立基于个性化体系差异的肿瘤精准治疗新理论范式与大数据算法模型。

欢迎对肿瘤治疗方向感兴趣的学生、助研、博后加入团队!

教学情况

本科《基础医学导论》《医学前沿进展》《损伤与反应》《基础医学实验技术》;硕士《医学免疫学》《免疫学前沿进展》《细胞与分子生物学》;博士《免疫新进展》。

获批资助项目

2021武汉大学人才引进项目

2021武汉市“武汉英才”优秀青年人才项目

2021 湖北省重点联系专家

近期代表性论文

  1. Ke Gong, Gao Guo, Nicole A. Beckley, Xiaoyao Yang, Yue Zhang, David E. Gerber, John D. Minna, Sandeep Burma, Dawen Zhao, Esra A. Akbay & Amyn A. Habib* Comprehensive targeting of resistance to inhibition of RTK signaling pathways by using glucocorticoids. Nature Communications. 2021 12:7014 (Processed to a Phase II Clinical Trial: NCT04497584)

  2. Ke Gong, Gao Guo, Nishah Panchani, Matthew E. Bender, David E. Gerber, John D. Minna, Farjana Fattah, Boning Gao, Michael Peyton, Kemp Kernstine, Bipasha Mukherjee, Sandeep Burma, Cheng-Ming Chiang, Shanrong Zhang, Adwait Amod Sathe, Chao Xing, Kathryn H. Dao, Dawen Zhao, Esra A. Akbay, and Amyn A. Habib* EGFR inhibition triggers an adaptive response by co-opting antiviral signaling pathways in lung cancer. Nature Cancer. 2020 1(4): 394–409. (Highlighted by Nature Cancer,Cancer Discovery and Nature Reviews Cancer)

  3. Ke Gong#, Gao Guo#, David E Gerber, Boning Gao, Michael Peyton, Chun Huang, John D Minna, Kimmo J Hatanpaa, Kemp Kernstine, Ling Cai, Yang Xie, Hong Zhu, Farjana J Fattah, Shanrong Zhang, Masaya Takahashi, Bipasha Mukherjee, Sandeep Burma, Jonathan Dowell, Kathryn Dao, Vassiliki A Papadimitrakopoulou, Victor Olivas, Trever G Bivona, Dawen Zhao, Amyn A Habib*. TNF-driven adaptive response mediates resistance to EGFR inhibition in lung cancer. Journal of Clinical Investigation. 2018 128(6):2500-2518 #Co-first author

  4. Ke Gong*, Gao Guo, Nicole Beckley, Yue Zhang, Xiaoyao Yang, Mishu Sharma, Amyn A.Habib* Tumor necrosis factor in lung cancer: Complex roles in biology and resistance to treatment. Neoplasia. 2021 23(2):189-196

  5. Zhi-Hao Wang#, Ke Gong#, Xia Liu, Zhentao Zhang, Xiaoou Sun, Zheng Wei, Shan Yu, Fredric P Manfredsson, Ivette Sandoval, Peter Johnson, Jianping Jia, Jian-Zhi Wang, and Keqiang Ye* C/EBPβ regulates Delta-secretase expression and mediates pathogenesis in mouse models of Alzheimer’s Disease. Nature Communications. 2018 9(1):1784 #Co-first author

  6. Ke Gong, Zhenxing Zhang, Yicheng Chen, Hong-Bing Shu, Wenhua Li* Extracellular signal-regulated kinase, receptor interacting protein, and reactive oxygen species regulate shikonin-induced autophagy in human hepatocellular carcinoma. European Journal of Pharmacology. 2014 738:142-52

  7. Ke Gong#, Chao Chen#, Yao Zhan, Yan Chen, Zebo Huang, Wenhua Li*. Autophagy-related gene 7 (Atg7) and reactive oxygen species (ROS)/extracellular-signal-regulated kinase (ERK) regulate tetrandrine-inducedautophagy in human hepatocellular carcinoma. Journal of Biological Chemistry.2012, 287:35576-88 #Co-first author

  8. Ke Gong, Jia Xie, Hong Yi, Wenhua Li*. CS055 (Chidamide/HBI-8000), a novel histone deacetylase inhibitor, induces G1-arrest, ROS-dependent apoptosis and differentiation in human leukemia cells. Biochemical Journal. 2012, 443:735-46

  9. Ke Gong, Wenhua Li* Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinoma. Free Radical Biology and Medicine. 2011, 51:2259-71.

  10. Gao Guo, Ke Gong, Nicole Beckley, Yue Zhang, Xiaoyao Yang, Rati Chkheidze, Kimmo J Hatanpaa, Tomas Garzon-Muvdi, Prasad Koduru, Arifa Nayab, Jennifer Jenks, Adwait Amod Sathe, Yan Liu, Chao Xing, Shwu-Yuan Wu, Cheng-Ming Chiang, Bipasha Mukherjee, Sandeep Burma, Bryan Wohlfeld, Toral Patel, Bruce Mickey, Kalil Abdullah, Michael Youssef, Edward Pan, David E Gerber, Shulan Tian, Jann N Sarkaria, Samuel K McBrayer, Dawen Zhao, Amyn A Habib* EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation. Nature Cell Biology. 2022 Aug 1

  11. Guo G, Gong K, Puliyapaddamba VT, Pan E, Mukherjee B, Damanwalla Z, Bharia S, Hatanpaa KJ, Zhao D, Burma S, and Habib AA* Efficacy of EGFR plus TNF inhibition in a preclinical model of temozolomide-resistant glioblastoma. Neuro-Oncology. 2019 Nov 8;10(1):5108

  12. Guo G, Gong K, Ali S, Ali N, Shallwani S, Hatanpaa KJ, Pan E, Mickey B, Burma S, Wang DH, Kesari S, Sarkaria JN, Zhao D, Habib AA* A TNF-JNK-Axl-ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma. Nature Neuroscience. 2017 Aug;20(8):1074-1084

  13. Guo G, Gong K, Habib AA* Analysis of Constitutive EGFR Signaling Regulating IRF3 Transcriptional Activity in Cancer Cells. Methods in Molecular Biology. 2017 1652 183-189

  14. Guo G, Gong K, Wohlfeld B, Hatanpaa KJ, Zhao D, Habib AA* Ligand-Independent EGFR Signaling. Cancer Research. 2015 Sep 1;75(17):3436-41

  15. Song Y, Gong K, Yan H, Hong W, Wang L, Wu Y, Li W*, Li W*, Cao Z* Sj7170, a unique dual-function peptide with a specific α-chymotrypsin inhibitory activity and a potent tumor-activating effect from scorpion venom. Journal of Biological Chemistry 2014 289 (17), 11667-11680

  16. Zhan Y, Gong K, Chen C, Wang H, Li W* P38 MAP kinase functions as a switch in MS-275-induced reactive oxygen species-dependent autophagy and apoptosis in human colon cancer cells. Free Radical Biology and Medicine 2012 53 (3), 532-543

  17. Liu C, Gong K, Mao X, Li W* Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma. International Journal of Cancer 2011 129 (6), 1519-1531

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