关东铣
个人简介：
关东铣教授，2015年于中国科学院上海生命科学研究院获得博士学位；2015-2016年留院（中国科学院上海生命科学研究院）工作；2016-2024年在美国哈佛大学医学院/波士顿儿童医院继续从事博士后研究。2024年加盟南京大学现代生物研究院，组建"系统生物学与神经代谢调控" 实验室。
关东铣教授长期聚焦于肥胖代谢性疾病及肿瘤相关的机制与转化研究，围绕内质网应激开展了其与系统性炎症、糖脂代谢紊乱、瘦素抵抗、神经元敏感性及肿瘤干细胞的适应性耐药等多角度的探索并取得了一系列原创性的研究成果：首次揭示乙酰化修饰对瘦素受体的敏感性调控机制，重新定义了瘦素抵抗(Cell Metabolism, 2024)；首次实现靶向激活瘦素受体，取得多年来应对肥胖代谢病的历史性突破，并发现了多项高转化潜力的化学小分子(Cell Metabolism, 2024)； 首次揭示蛋白质顺反异构折叠紊乱的感应机制和致病机理(Cell Metabolism, 2022)；首次揭示系统性IL1/IL1R1炎症信号与缓解内质网应激的共偶联机制(Nature Medicine, 2019)；首次挑战并证明了临床随机对照双盲实验评价体系的不完备性(Hepatology, 2015)；率先构建并利用临床来源的肝癌活体库揭示了肿瘤干细胞对分子靶向药的适应性耐药机理与分化治疗可行性等(Hepatology, 2015; Journal of Hepatology, 2013)。为相关疾病的临床诊疗提供了建设性的参考方案。迄今以独立第一作者/共同第一作者及共同作者在 Nature Medicine, Cell Metabolism (4x), Hepatology (2x), Journal of Hepatology (2x), Science, Nature Cell Biology, Nature Communication，Immunity, Cell Research, Gastroenterology等国际知名学术期刊发表了25篇研究型论文并申请了多项专利；相关工作得到Faculty of 1000, Cell Metabolism等专评，并被多个国际、国内媒体相继报道；并应邀担任多个杂志审稿人及客座编辑。
研究方向：
实验室目前以大数据、多模态、多学科、高前沿技术相融合的策略，探索重大疾病中以临床转化为导向的神经代谢调控与新药研发，包括：1，中枢关键核团神经元的敏感性陷阱感知；2，中枢与外周的多元化场景式交互；3，细胞功能性重塑与创新性药物研发等。
欢迎相关学科背景的优秀学生申请硕士/博士研究生，也欢迎有兴趣的青年学者加入。
联系邮箱：
实验室网站：https://www.x-mol.com/groups/DongxianGuanlab?lang=zh
代表性论文：
1. Central Inhibition Of Hdac6 Re-Sensitizes Leptin Signaling During Obesity To Induce Profound Weight Loss. Guan Dongxian(关东铣), Men Yuqin, Bartlett Alexander, Salazar Hernández Mario Andrés, Xu Jie, Yi Xinchi, Li Husong, Kong Dong, Mazitschek Ralph, Ozcan Umut. Cell Metabolism. Volume 36, Issue 4, 2 Apr 2024, 857-876).
2. FKBP11 Rewires UPR Signaling To Promote Glucose Homeostasis In Type2 Diabetes And Obesity. Herrema Hilde*, Guan Dongxian*(关东铣), Choi Jae Won*, Feng Xudong, Salazar Hernandez Mario Andres, Faruk Farhana, Auen Thomas, Boudett Eliza, Tao Rongya, Chun Hyonho, Ozcan Umut. Cell Metabolism. Volume 34, Issue 7, 5 July 2022, 1004-1022.e8. (*Equal contribution)
3. IL1R1 Is Required For Celastrol’s Leptin Sensitization And Anti-Obesity Effects. Feng Xudong*, Guan Dongxian*(关东铣), Auen Thomas, Choi Jae Won, Salazar-Hernandez Mario Andres, Lee Jaemin, Chun Hyonho, Faruk Farhana, Kaplun Esther, Herbert Zachary, Copps Kyle D, Ozcan Umut. Nature Medicine. 2019 Apr;25(4):575-582. (*Equal contribution)
4. Sorafenib Enriches Epcam Positive Tumor Initiating Cells And Exacerbates A Subtype Of Hepatocellular Carcinoma Through TSC2-AKT Cascade. Guan Dongxian(关东铣), Shi Jie, Zhang Yang, Zhao Jiangsha, Long Lingyun, Chen Tianwei, Zhang Eebin, Feng Yuanyuan, Bao Wendai, Deng Yuezhen, Qiu Lin, Zhang Xueli, Koeffler HP, Cheng Shuqun, Li Jingjing, Xie Dong. Hepatology. 2015 Dec;62(6):1791-803.
5. All-Trans Retinoic Acid Potentiates The Chemotherapeutic Effect Of Cisplatin By Inducing Differentiation Of Tumor Initiating Cells In Liver Cancer. Zhang Yang*, Guan Dongxian*(关东铣), Shi Jie, Gao Hong, Li Jingjing, Zhao Jiangsha, Qiu Lin, Liu Jiang, Li Nan, GuoWeixing, Xue Jie, Zhou Feiguo, Wu Mengchao, Wang Hongyang, Xie Dong, Cheng Shuqun. Journal of Hepatology. 2013 Dec;59(6):1255-63. (*Equal contribution)
6.Gut Microbial Co-Metabolite 2-Methylbutyrylcarnitine Exacerbates Thrombosis Via Binding To And Activating Integrin Α2β1. Huang Kan, Li Zilun, He Xi, Dai Jun, Huang Bingding, Shi Yongxia, Fan Dongxiao, Zhang Zefeng, Liu Yunchong, Li Na, Zhang Zhongyu, Peng Jiangyun, Liu Chenshu, Zeng Renli, Cen Zhipeng, Wang Tengyao, Yang Wenchao, Cen Meifeng, Li Jingyu, Yuan Shuai, Zhang Lu, Hu Dandan, Huang Shuxiang, Chen Pin, Lai Peilong, Lin Liyan, Wen Jielu, Zhao Zhengde, Huang Xiuyi, Yuan Lining, Zhou Lifang, Wu Haoliang, Huang Lihua, Feng Kai, Wang Jian, Liao Baolin, Cai Weiping, Deng Xilong, Li Yueping, Li Jianping, Hu Zhongwei, Yang Li, Li Jiaojiao, Zhuo Youguang, Zhang Fuchun, Lin Lin, Luo Yifeng, Zhang Wei, Ni Qianlin, Hong Xiqiang, Chang Guangqi, Zhang Yang, Guan Dongxian(关东铣), Cai Weikang, Lu Yutong, Li Fang, Yan Li, Ren Meng, Li Linghua, Chen Sifan. Cell Metabolism. 2024 Feb 20:S1550-4131(24)00014-7.
7. Metabolic Orchestration Of Cell Death By AMPK-Mediated Phosphorylation Of RIPK1. Zhang Tao, Xu Daichao, Trefts Elijah, Lv Mingming, Inuzuka Hiroyuki, Song Guobin, Liu Min, Lu Jianlin, Liu Jianping, Chu Chen, Wang Min, Wang Huibing, Meng Huyan, Liu Hui, Zhuang Yuan, Xie Xingxing, Dang Fabin, Guan Dongxian(关东铣), Men Yuqin, Jiang Shuwen, Jiang Cong, Dai Xiaoming, Liu Jing, Wang Zhen, Yan Peiqiang, Wang Jingchao, Tu Zhenbo, Babuta Mrigya, Erickson Emily, Hillis Alissandra L, Dibble Christian C, Asara John M, Szabo Gyongy, Sicinski Piotr, Miao Ji, Lee YuRu, Pan Lifeng, Shaw Reuben J, Yuan Junying, Wei Wenyi. Science. 2023 Jun 30;380(6652):1372-1380.
8. Prolonged Hypoxia Alleviates Prolyl Hydroxylation-Mediated Suppression Of RIPK1 To Promote Necroptosis And Inflammation. Zhang Tao, Xu Daichao, Liu Jianping, Wang Min, Duan Lijuan, Liu Min, Meng Huyan, Zhuang Yuan, Wang Huibing, Wang Yingnan, Lv Mingming, Zhang Zhengyi, Hu Jia, Shi Linyu, Guo Rui, Xie Xingxing, Liu Hui, Erickson Emily, Wang Yaru, Yu Wenyu, Dang Fabin, Guan Dongxian(关东铣), Jiang Cong, Dai Xiaoming, Inuzuka Hiroyuki, Yan Peiqiang, Wang Jingchao, Babuta Mrigya, Lian Gewei, Tu Zhenbo, Miao Ji, Szabo Gyongyi, Fong Guohua, Karnoub Antoine E, Lee Yu-Ru, Pan Lifeng, Kaelin Jr William G, Yuan Junying, Wei Wenyi. Nature Cell Biology. 2023 Jul;25(7):950-962. doi: 10.1038/s41556-023-01170-4.
9. Imatinib And Methazolamide Ameliorate COVID-19-Induced Metabolic Complications Via Elevating ACE2 Enzymatic Activity And Inhibiting Viral Entry. Li Zilun, Peng Meixiu, Chen Pin, Liu Chenshu, Hu Ao, Zhang Yixin, Peng Jiangyun, Liu Jiang, Li Yihui, Li Wenxue, Zhu Wei, Guan Dongxian(关东铣), Zhang Yang, Chen Hongyin, Li Jiuzhou, Fan Dongxiao, Huang Kan, Lin Fen, Zhang Zefeng, Guo Zeling, Luo Hengli, He Xi, Zhu Yuanyuan, Li Linghua, Huang Bingding, Cai Weikang, Gu Lei, Lu Yutong, Deng Kai, Yan Li, Chen Sifan. Cell Metabolism. 2022, 34 (3), 424-440. e7.
10.Targeting USP9X–AMPK Axis In ARID1A-Deficient Hepatocellular Carcinoma. Zhang Fengkun, Ni Qianzhi, Wang Kang, Cao Huijun, Guan Dongxian(关东铣), Zhang ErBin, Ma Ning, Wang Yiyang, Zheng Qianwen, Xu Sheng, Zhu Bing, Chen Tianwei, Xia Ji, Qiu Xiaosong, Ding Xufen, Jiang Hao, Qiu Lin, Wang Xiang, Chen Wei, Cheng Shuqun, Xie Dong, Li Jingjing. Cellular and Molecular Gastroenterology and Hepatology. 2022, 14 (1), 101-127.
11. The Human Novel Gene LNC-HC Inhibits Hepatocellular Carcinoma Cell Proliferation By Sequestering Hsa-Mir-183-5p. Lan Xi, Wu Nan, Wu Litao, Qu Kai, Osoro Ezra Kombo, Guan Dongxian(关东铣), Du Xiaojuan, Wang Bo, Chen Sifan, Miao Ji, Ren Juan, Liu Li, Li Haiyun, Ning Qilan, Li Dongmin, Lu Shemin. Molecular Therapy Nucleic Acids. 2020 Jun 5; 20:468-479.
12. CHML Promotes Liver Cancer Metastasis By Facilitating Rab14 Recycle. Chen Tianwei, Yin Fenfen, Yuan Yanmei, Guan Dongxian(关东铣), Zhang Erbin, Zhang Fengkun, Jiang Hao, Ma Ning, Wang Jingjing, Ni Qianzhi, Qiu Lin, Feng Jing, Zhang Xueli, Bao Ying, Wang Kang, Cheng Shuqun, Wang Xiaofan, Wang Xiang, Li Jingjing, Xie Dong. Nature Communication. 2019 Jun 7;10(1):2510.
13. WISP3 Suppresses Hepatocellular Carcinoma Progression By Negative Regulation Of Β-Catenin/TCF/LEF Signalling. Gao Hong, Yin Fenfen, Guan Dongxian（关东铣）, Feng Yuxiong, Zheng Qianwen, Wang Xiang, Zhu Min, Zhang Xueli, Cheng Shuqun, Chen Tianwei, Jiang Hao, Zhang Erbin, Wang Jingjing, Ni Qianzhi, Yuan Yanmei, Zhang Fengkun, Ma Ning, Cao Huijun, Wang Yikang, Li Jingjing, Xie Dong. Cell Proliferation. 2019 Feb 22: e12583.
14. Lipocalin 2 Does Not Play A Role In Celastrol-Mediated Reduction In Food Intake And Body Weight. Feng Xudong, Guan Dongxian（关东铣）, Auen Thomas, Choi Jae Won, Salazar-Hernandez Mario Andres, Faruk Farhana, Copps Kyle D, Ozcan Umut. Scientific Reports. 2019 Sep 5;9(1):12809.
15. Chemerin Suppresses Hepatocellular Carcinoma Metastasis Through CMKLR1-PTEN-Akt Axis. Li Jingjing, Yin Hongkun, Guan Dongxian（关东铣）, Zhao Jiangsha, Feng Yuxiong, Deng Yuezhen, Wang Xiang, Li Nan, Wang Xiaofan, Cheng Shuqun, Bao Ying, Xie Dong. British Journal of Cancer. 2018 May;118(10):1337-1348.
16. Cilia Loss Sensitizes Cells To Transformation By Activating The Mevalonate Pathway. Deng Yuezhen, Cai Zhen, Shi Shuo, Jiang Hao, Shang Yurong, Ma Ning, Wang Jingjing, Guan Dongxian（关东铣）, Chen Tianwei, Rong Yefei, Qian Zhenyu, Zhang Erbin, Feng Dan, Zhou Quanli, Du Yinan, Liu Dongping, Huang Xingxu, Liu Luming, Chin Eugene, Li Dangsheng, Wang Xiaofan, Zhang Xueli, Xie Dong. Journal of Experimental Medicine. 2018 Jan 2;215(1):177-195.
17. Triosephosphate Isomerase 1 Suppresses Growth, Migration And Invasion Of Hepatocellular Carcinoma Cells. Jiang Hao, Ma Ning, Shang Yurong, Zhou Wentao, Chen Tianwei, Guan Dongxian（关东铣）, Li Jingjing, Wang Jingjing, Zhang Erbin, Feng Yuanyuan, Yin Fenfen, Yuan Yanmei, Fang Yuanyuan, Qiu Lin, Xie Dong, Wei Dongzhi. Biochemical and Biophysical Research Communications. 2017 Jan 22;482(4):1048-1053.
18. Iron Overload In Hereditary Tyrosinemia Type 1 Induces Liver Injury Through Sp1/Tfr2/Hepcidin Axis. Bao Wendai, Yao Fan, Deng Yuezhen, Li Jingjing, Long Lingyun, Guan Dongxian（关东铣）, Qian Zhenyu, An Peng, Feng Yuanyuan, He Zhiying, Wang Xiaofan, Koeffler HP, Hu Ronggui, Wang Fudi, Xie Dong. Journal of Hepatology. 2016 Jul;65(1):137-45.
19. Recruitment Of Phosphatase PP2A By RACK1 Adaptor Protein Deactivates Transcription Factor IRF3 And Limits Type I Interferon Signaling. Long Lingyun, Deng Yuezhen, Yao Fan, Guan Dongxian(关东铣), Feng Yuanyuan, Jiang Hao, Li Xiaobin, Hu Pingting, Lu Xingcheng, Wang Hui, Li Jingjing, Gao Xiang, Xie Dong. Immunity. 2014 Apr 17;40(4):515-29.
20. RACK1 Modulates NF-Κb Activation By Interfering With The Interaction Between TRAF2 And The IKK Complex. Yao Fan, Long Lingyun, Deng Yuezhen, FengYuanyuan, Ying Guoyuan, BaoWendai, Li Guo, Guan Dongxian(关东铣), Zhu Yingqiu, Li Jingjing, Xie Dong. Cell Research. 2014 Mar;24(3):359-71.
21. Critical Roles Of P53 In Epithelial-Mesenchymal Transition And Metastasis Of Hepatocellular Carcinoma Cells. Wang Zheng, Jiang Yuhui, Guan Dongxian（关东铣）, Li Jingjing, Yin Hao, Pan Yi, Xie Dong, Chen Yan. PLoS One. 2013 Sep 2;8(9):e72846.
22. Roles Of Fibroblast Growth Factor-Inducible 14 In Hepatocellular Carcinoma. Li Nan, Hu Wenjun, Shi Jie, Xue Jie, Guo Weixing, Zhang Yang, Guan Dongxian（关东铣）, Liu Shupeng, Cheng Yuqiang, Wu Mengchao, Xie Dong, Liu Shanrong, Cheng Shuqun. Asian Pacific Journal of Cancer Prevention. 2013;14(6):3509-14.
23. RACK1 Suppresses Gastric Tumorigenesis By Stabilizing The Β-Catenin Destruction Complex. Deng Yuezhen, Yao Fan, Li Jingjing, Mao Zhengfa, Hu Pingting, Long Lingyun, Li Guo, Ji Xiaodan, Shi Shuo, Guan Dongxian(关东铣), Feng Yuanyuan, Cui Lei, Li Dangsheng, Liu Yong, Du Xiang, Guo Mingzhou, Xu Liyan, Li Enmin, Wang Hongyang, Xie Dong. Gastroenterology. 2012 Apr;142(4):812-823.e15.
24. Sorafenib Suppresses Postsurgical Recurrence And Metastasis Of Hepatocellular Carcinoma In An Orthotopic Mouse Model. Feng Yuxiong, Wang Tao, Deng Yuezhen, Yang Pengyuan, Li Jingjing, Guan Dongxian（关东铣）, Yao Fan, Zhu Yinqiu, Qin Ying, Wang Hui, Li Nan, Wu Mengchao, Wang Hongyang, Wang Xiaofan, Cheng Shuqun, Xie Dong. Hepatology. 2011 Feb;53(2):483-92. doi: 10.1002/hep.24075.
25. Tumor Initiating Cells In Esophageal Squamous Cell Carcinomas Express High Levels Of CD44. Zhao Jiangsha, Li Wenjun, Ge Di, Zhang Peijing, Li Jingjing, Lu Chunlai, Ji Xiaodan, Guan Dongxian（关东铣）, Gao Hong, Xu Liyan, Li Enmin, Soukiasian Harmik, Koeffler HP, Wang Xiaofan, Xie D. PLoS One. 2011;6(6):e21419.