博士生导师
向宽辉 副研究员
Email: kxiang@bjmu.edu.cn
实验室网站:https://www.x-mol.com/groups/kxiang_pku
研究方向
病毒感染和致病模型的建立与优化
病毒与宿主相互作用的机制研究
个人简介
2022.08-目前 北京大学,病原生物学,副研究员
2017.08-2022.07 北京大学,病原生物学,讲师
2014.09-2016.08 美国洛克菲勒大学,诺奖获得者Charles M. Rice实验室,联合培养
2011.09-2017.07 北京大学,病原生物学,博士
2006.09-2011.07 河北医科大学,医学检验,学士
乙型肝炎病毒(HBV)感染可导致慢性化、肝硬化甚至肝癌,造成重大的公共卫生问题。目前,治疗HBV的药物主要是核苷(酸)类似物和干扰素。核苷类似物不能抑制cccDNA而不能根治HBV感染,因而需要长期甚至终身服药,也因此更容易导致耐药问题产生。虽然有许多研究报道干扰素可以清除病毒,达到“功能性治愈”,但是其副作用等因素限制其广泛使用。同时,由于有限的HBV细胞感染模型以及动物模型限制了HBV的深入研究。因此,建立和优化新的HBV感染模型和致病模型,深入研究病毒与宿主的相互作用,为寻找新的抗病毒药物靶点提供基础。本课题组建立了HBV高效感染的细胞模型,应用于病毒感染及抗病毒药物筛选及评价;发现干扰素介导的TRIM56通过泛素化NF-kB通路进而抑制HBV核心启动子活性而抑制HBV复制的机制;发现HBV S基因的变异及病毒感染,复制及分泌的影响,揭示病毒逃逸宿主的新机制。
此外,自2019年底出现的新冠肺炎(Corona virus Disease 2019, COVID-19)以来,COVID-19造成了全球大流行并带给人类极大的生命健康危害,特别是新冠病毒(Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2)在全球流行过程中,发生了几次严重的突变株流行,给世界疫情防控带来新的巨大挑战。由于人们对SARS-CoV-2感染及与宿主相互作用机制的了解较少,针对SARS-CoV-2的已知药物靶点有限,限制了抗SARS-CoV-2药物的研发,因而深入研究SARS-CoV-2的感染及与宿主的相互作用机制,将有助于发现新的抗病毒药物靶点。本课题组首次发现母乳成分(乳铁蛋白、粘蛋白1等)具有显著抗SARS-CoV-2的作用,并合作发现中药成分通过抑制SARS-CoV-2的受体结合而抑制SARS-CoV-2的感染能力,为后续的药物研发提供基础。
发表SCI论文26篇,代表性工作发表于Journal of Hepatology、Signal Transduction and Targeted Therapy、Journal of Advanced Research、Stem Cell Reports、Antiviral Research等期刊。近五年作为负责人主持国自然面上项目、青年项目等8项科研项目。于2021年入选北京市科协青年人才托举工程项目。相关研究成果获中华医学科技奖二等奖(第五完成人,5/15)。此外,相关成果申请7项国家发明专利(2项已获授权)。
获奖情况
2022年,北京大学优秀教学成果一等奖(2/11)
2021年,中华医学科技奖二等奖(5/15)
2021年,北京大学青年岗位能手
2020年,基础医学院青年教师奖励基金
2019/2018年,国际HBV大会Travel Award
2019年,优秀论文引用奖
代表论著(#共同第一作者,*通讯作者)
1. Kuanhui Xiang, Eleftherios Michailidis, Hai Ding, Ya-Qin Peng, Ming-Ze Su, Yao Li, Xue-En Liu, Viet Loan Dao Thi, Xian-Fang Wu, William M Schneider, Charles M Rice, Hui Zhuang*, Tong Li *. Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA. Journal of Hepatology, 2017, 66(2):288-296 (IF: 30.08)
2. Huahao Fan#, Bixia Hong#, Yuqian Luo#, Qi Peng#, Liqin Wang, Xiangshu Jin, Yangzhen Chen, Yunjia Hu, Yi Shi, Tong Li, Hui Zhuang, Yi-Hua Zhou*, Yigang Tong*, Kuanhui Xiang*. The effect of whey protein on viral infection and replication of SARS-CoV-2 and pangolin coronavirus in vitro. Signal Transduction and Targeted Therapy, 2020, 5(1):275 (Research Letter, 封面文章,IF:38.1)
3. Xinyuan Lai#, Chuanyun Li#, Chengang Xian, Zihang Pan, Kai Zhang, Lei Wang, Bingqing Xie, Junning Cao, Jihang Shi, Juan Deng, Shichun Lu, Hongkui Deng, Hui Zhuang, Tong Li1*, Yan Shi3*, Kuanhui Xiang*. Generation of functionally competent hepatic stellate cells from human stem cells to model liver fibrosis in vitro. Stem Cell Reports, 2022, 17:1-17 (IF:7.29, Top)
4. Yang Yi#, Junhua Li#, Xinyuan Lai#, Meng Zhang, Yi Kuang, Yang-Oujie Bao, Rong Yu, Wei Hong, Elishiba Muturi, Heng Xue, Hongping Wei, Tong Li, Hui Zhuang, Xue Qiao, Kuanhui Xiang*, Hang Yang*, Min Ye*. Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection. Journal of Advanced Research, 2021, 36:201-210 (IF: 12.82)
5. Kai Zhang#, Xinyuan Lai#, Ji Song, Lingyuan He, Luwei Wang, Guomin Ou, Xing Tian, Lei Wang, Juan Deng, Jiajia Zhang, Chuanyun Li, Hui Zhuang*, Tong Li*, Kuanhui Xiang*. A novel cell culture model reveals the viral interference during hepatitis B and C virus coinfection. Antiviral Research, 2021, 189:105061 (IF: 10.1)
6. Xing Tian#, Huijun Dong#, Xinyuan Lai, Guomin Ou, Junning Cao, Jihang Shi, Chengang Xiang, Lei Wang, Xuechao Zhang, Kai Zhang, Ji Song, Juan Deng, Hongkui Deng, Shichun Lu, Hui Zhuang*, Tong Li*, Kuanhui Xiang*. TRIM56 impairs HBV infection and replication by inhibiting HBV core promoter activity. Antiviral Research, 2022, 105406 (IF: 10.1)
7. Xinyuan Lai#, Yanying Yu#, Wei Xian#, Fei Ye#, Xiaohui Ju, Yuqian Luo, Huijun Dong, Yi-Hua Zhou, Wenjie Tan, Hui Zhuang, Tong Li, Xiaoyun Liu*, Qiang Ding*, Kuanhui Xiang*. Identified human breast milk compositions effectively inhibit SARS-CoV-2 and variants infection and replication. iScience, 2022, 25(4): 104136 (IF: 6.11)
8. Yuqian Luo#, Kuanhui Xiang#, Jingli Liu, Ji Song, Jing Feng, Jie Chen, Yimin Dai, Yali Hu, Hui Zhuang*, Yihua Zhou*. Inhibition of In Vitro Infection of Hepatitis B Virus by Human Breastmilk. Nutrients, 2022, 14(8):1561 (IF: 6.71)
9. Chengang Xiang#, Yuanyuan Du#, Gaofan Meng#, Liew Soon Yi, Shicheng Sun, Nan Song, Xiaonan Zhang, Yiwei Xiao, Jie Wang, Zhigang Yi, Yifang Liu, Bingqing Xie, Min Wu, Jun Shu, Da Sun, Jun Jia, Zhen Liang, Dong Sun, Yanxiang Huang, Yan Shi, Jun Xu, Fengmin Lu, Cheng Li, Kuanhui Xiang, Zhenghong Yuan*, Shichun Lu*, Hongkui Deng*. Long-term functional maintenance of primary human hepatocytes in vitro. Science, 2019, 364(6438):399-402 (IF: 63.71)
10. Xianfang Wu#, Viet Loan Dao Thi#, Peng Liu, Constantin N Takacs, Kuanhui Xiang, Linda Andrus, Jérôme Gouttenoire, Darius Moradpour, Charles M Rice. Pan-Genotype Hepatitis E Virus Replication in Stem Cell-Derived Hepatocellular Systems. Gastroenterology, 2018, 154(3): 663-674 (IF: 33.88)
11. Bingqing Xie#, Da Sun#, Yuanyuan Du#, Jun Jia, Shicheng Sun, Jun Xu, Yifang Liu, Chengang Xiang, Sitong Chen, Huangfan Xie, Qiming Wang, Guangya Li, Xuehui Lyu, Hui Shen, Shiyu Li, Min Wu, Xiaonan Zhang, Yue Pu, Kuanhui Xiang, Weifeng Lai, Peng Du, Zhenghong Yuan, Cheng Li, Yan Shi*, Shichun Lu*, Hongkui Deng*. A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts. Cell Research, 2019, 29(9):696-710 (IF: 46.30)