联系方式

实验室位置:

澳门新葡游戏网3号楼5楼

Email:

kegong@whu.edu.cn

龚克   教授

职称职务:教授,博士/硕士研究生导师,国家级人才计划入选者

学科专业:免疫学

研究方向:肿瘤细胞信号转导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:澳门新葡游戏网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

2021-2022 澳门新葡游戏网 特聘研究员
2022-今   澳门新葡游戏网 教授

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实体肿瘤,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。

前期在美国课题组的研究发现,引发炎症反应并能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),正在美国德州大学西南医学中心开展II期临床试验:NCT04497584(2020-2024)。另外,利用一种新算法模型分析胶质瘤数据,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),经课题组实验验证,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(Guo et al. Nature Cell Biology,2022),揭示了胶质瘤EGFR-TKI临床失败的可能原因,相关III期临床试验NCT05326464(2022-2026)正在开展。

目前,本人负责的独立课题组研究兴趣主要从肿瘤细胞的视角出发,了解它们如何生存发展并抵御内外环境中的各种不利因素,以弱克强,反侮为病,从对机制的探索中寻找攻克癌症的新策略。研究对象为肺癌、乳腺癌、肝癌等国内高发病的癌种。

具体内容包括:1)免疫、炎症、代谢、神经等信号通路介导的酪氨酸激酶靶向药物治疗抵抗的分子机制;2)围绕临床问题,结合整合组学与实验研究,挖掘影响肿瘤治疗响应、患者预后转归的肿瘤染色体变异相关的新型调控模式与治疗靶点;3)基于数据预测算法,发现个性化患者-精准药物相匹配的联合治疗新方案,并推动临床转化。

欢迎对肿瘤治疗研究以及信息学交叉方向感兴趣的学生、助研、博后加入团队!

教学情况

 

承担本科生课程《病原学与免疫学前沿技术》;参与本科生课程《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》,以及研究生课程《医学免疫学》《免疫学前沿进展》《细胞与分子生物学》《免疫新进展》的教学。


主要学术兼职

湖北省免疫学会常务理事;湖北省细胞生物学学会理事;湖北省病理生理学会常务理事

 

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

2022 国家级人才项目(执行期:2023-2025)

2023 国家自然科学基金面上项目(执行期:2024-2027)

 

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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