陆勇军（中大教授）

陆勇军（中大教授）的个人简介

陆勇军，男，博士，中山大学生命科学学院教授、博士生导师。

研究方向

病原细菌/人体微生物组与宿主互作-以效应蛋白为中心

微生物与其宿主之间的相互作用是生物物种间最复杂的相互作用之一。一方面，在与人类或者其它动植物宿主亿万年共同进化的过程中，共栖微生物（Commensal）成功适应了宿主环境，并对宿主的发育、免疫及神经系统都产生重要的影响；另一方面，病原菌（Pathogens）则能突破宿主的免疫屏障，实现感染。虽然抗生素和疫苗的发明使我们能对付大多数的病原细菌(Pathogenic bacteria)，但是，病原细菌也逐渐发展出了抵抗抗生素的策略，出现了超级抗性菌，使病原细菌特别是耐药性细菌又一次成为人类的重大威胁；同时，病原细菌还发展出了精巧复杂的毒力系统，以适应宿主体内环境、躲避或克服宿主的免疫体系，导致各种感染症甚至癌症等，其中最重要的毒力系统就是细菌的分泌系统(Secretion System)。通过相当于细菌“武器”的分泌系统，细菌可以向宿主体内分泌数量众多、功能各异的毒力蛋白-效应蛋白（Effector proteins，也就是细菌的“子弹”），效应蛋白与宿主细胞表面或宿主细胞中的各种靶点蛋白相互作用，改变宿主的各种信号传导途径如细胞凋亡、自噬和细胞周期等，从而适应宿主环境，克服宿主免疫系统的攻击，达到让细菌自身在宿主内增殖的目的。

研究微生物和宿主相互作用的学科称为细胞微生物学（Cellular Microbiology），细菌效应蛋白功能的阐明是该学科研究的重点。（1）阐明效应蛋白的生化功能，可以让我们更深入理解病原细菌致病以及适应宿主环境的分子机制；（2）以这些效应蛋白为工具，发现宿主固有免疫（Innate Immunity）调控的新途径，是免疫学的新领域；（3）效应蛋白本身还可以作为抗菌药物作用的理想靶位点，研发针对这些效应蛋白的活性先导物（相当于钝化或收缴细菌的“子弹”），有可能获得避免耐药性产生的新型抗生素；（4）可以运用合成生物学（Synthetic Biology）策略在微生物细胞、癌细胞或免疫细胞中构建效应蛋白调控回路(Circuit) ，实现对疾病相关细胞活性的人工调控。

围绕以上方向，我们的研究兴趣具体如下（详见主页中的“研究兴趣”栏目）：

（1）效应蛋白的生化功能及宿主免疫反应机制以目前临床上典型的胞内病原细菌嗜肺军团菌（Legionella pneumophila）、结核分枝杆菌（Mycobacterium tuberculosis）以及重要的植物病原细菌茄科劳尔氏菌（Ralstonia solanacearum）为模型，重点研究其致病的关键效应蛋白的表达调控及其生化功能，阐明这些蛋白与宿主靶蛋白相互作用进而调整宿主免疫系统的分子机制。

（2）靶向效应蛋白的抗结核药物研制结核分枝杆菌是结核病的病原，感染了我国近三分之一的人口，是国人健康的重大威胁，急需新的抗结核药物。我们以结核分枝杆菌关键效应蛋白为靶点，建立相应的筛选系统，从微生物代谢产物中筛选效应蛋白的抑制剂，并研究其作用机制，期望获得新型的、能避免耐药产生的新型抗结核药物。

（3）肠道微生物组与宿主的互作及其分子机制肠道菌群是肠道内寄居的种类繁多的微生物的总称。肠道微生物是代谢的重要参与者，同时代谢产生的脂肪酸等促进肠道上皮细胞生长与分化。肠道菌群之间可以通过如分泌系统分泌的效应蛋白和群感效应（Quorum sensing）等维持菌群的平衡。肠道菌群失调（dysbiosis）会增加疾病的易感性，包括胃肠道疾病、代谢类疾病（如肥胖、糖尿病等）、免疫类疾病、精神类疾病和癌症等。对肠道微生物组与疾病关系的研究，将为开发基于微生物的疾病诊断、疾病干预、治疗和益生菌产品的研发等提供基础。我们综合运用基因组学、代谢组学和生物信息学技术，研究肠道微生物组（microbiome）或肠道细菌及其效应蛋白和代谢产物与炎症和癌症等的发生、发展的关联性及其分子机制；同时，运用合成生物学的相关策略，建立重要肠道菌的分子遗传操作系统，以期实现对肠道细菌功能的精准调控。

讲授课程

1. 主讲本科生课程：必修课“生物技术学”、必修课“生物技术综合实验”

2. 参讲本科生课程：“生命科学引论”、逸仙学院教育部拔尖创新人才培养试验班课程“生物学前沿学术专题”

3. 合讲研究生课程“细胞微生物学”

论文专著

一、部分论文（2009--）

Qin Zeng, Junli Gong, Xiyuan Liu, Chen Chen, Xiaobo Sun, Huijuan Li, Yifan Zhou, ChunPing Cui, Yuge Wang, Yu Yang, Aimin Wu, Yaqing Shu, Xueqiang Hu, Zhengqi Lu, Song Guo Zheng*, Wei Qiu*, Yongjun Lu*.Gut dysbiosis and lack of short chain fatty acids in a Chinese cohort of patients with multiple sclerosis.Neurochemistry International,2019(129)104468.He L, Lin Y, Ge ZH, He SY, Zhao BB, Shen D, He JG, Lu YJ*. TheLegionella pneumophilaeffector WipA disrupts host F-actin polymerisation by hijacking phosphotyrosine signaling.Cellular Microbiology. 2019 Jan 31:e13014. doi: 10.1111/cmi.13014.Dongfeng Zhang, Yun Lin, Xi Chen, Wenting Zhao, Dongni Chen, Meng Gao, Qinglin Wang, Bin Wang, Haihong Huangu204e,Yongjun Luu204e, Yu Luu204e.Docking- and pharmacophore-based virtual screening for the identification of novel Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB) inhibitor with a thiobarbiturate scaffold.Bioorganic Chemistry, 2019, 85:229u2013239.Jia-Hua Huang, Jian-Ming Lv, Qiao-Zhen Wang, Jian Zou, Yong-Jun Lu, Qing-Lin Wang, Dong-Ni Chen, Xin-Sheng Yao, Hao Gao and Dan Hu. Biosynthesis of an anti-tuberculosis sesterterpenoid asperterpenoid A.Organic & Biomolecular Chemistry, 2019 Jan 2; 17(2):248-251.LUO X-W, LIN Y, LU Y-J, Zhou XF, Liu YH. Peptides and polyketides isolated from the marine sponge-derived fungus Aspergillus terreus SCSIO 41008 [J].Chinese Journal of Natural Medicines, 2019, 17(2): 149-154.Sun yunhao, Li Pai, Shen Dong, Wei Qiaoling, He Jianguo, Lu Yongjun*. TheRalstonia solanacearumeffector RipN suppresses plant PAMP-triggered immunity, localizes to the endoplasmic reticulum and nucleus, and alters the NADH/NAD+ ratio in Arabidopsis.Molecular Plant Pathology.2019,20(4):533-546. First published, 2018,Nov 30. doi: 10.1111/mpp.12773.Gong JL, Qiu W, Zeng Q, Liu XY, Sun XB, Li HJ, Yang Y, Wu AM, Bao J, Wang YG, Shu YQ, Hu XQ, Bellanti JA, Zheng SG, Lu YJ*, Lu ZQ*. Lack of short-chain fatty acids and overgrowth of opportunistic pathogens define dysbiosis of neuromyelitis optica spectrum disorders: A Chinese pilot study.Multiple Sclerosis Journal, 2018, Aug 16:1352458518790396.Yu Dai, Yun Lin, Xiaoyan Pang, Xiaowei Luo, Limbadri salendra, Junfeng Wang，Xuefeng Zhou, Yongjun Lu, Bin Yang, Yonghong Liu. Peptides from the Soft Coral-associated FungusSimplicilliumsp. SCSIO41209.Phytochemistry, 2018, 154:56u201362。Qian Jia, Yun Lin, Xue-jing Gou, Lei He, Dong Shen, Dong-ni Chen, Wei Xie *, Yong-jun Lu*. Legionella pneumophila effector WipA, a bacterial PPP protein phosphatase with PTP activity.Acta Biochimica et Biophysica Sinica. 2018, 50(6):547-554.GONG Junli, SUN Xiaoming, LIN Zhiyong, LU Hongfeng, LU Yongjun. Geochemical and microbial characters of sediment from the gas hydrate area in the Taixinan Basin, South China Sea.Acta Oceanol. Sin., 2017, 36(9):52u201364.Senhua Chen, Meng Ding; Weiyang Liu; Xishan Huang, Zhaoming Liu, Yongjun Lu, Hongju Liu, Zhigang She. Anti-inflammatory Meroterpenoids from the Mangrove Endophytic FungusTalaromyces amestolkiaeYX1.Phytochemistry, 2017 Nov 30;146:8-15.Hui Cui, Yun Lin, Mingchu Luo, Yongjun Lu, Xishan Huang, and Zhigang She. Diaporisoindoles A?C: Three Isoprenylisoindole Alkaloid Derivatives from the Mangrove Endophytic FungusDiaporthesp. SYSU-HQ3.Organic Letters, 2017, Oct 20;19(20):5621-5624.Qianqian Ji, Caiping Guo, Chen Xie, Yingdan Wu, Pei Zhang, Hui Li, Yongjun Lu*. Genetically engineered cell lines for a1-antitrypsin expression.Biotechnology Letters, 2017, 39:1471-1476.Senhua Chen, Liqing He, Dongni Chen, Runlin Cai, Yuhua，Long, Yongjun Lu* and Zhigang She*. Talaramide A, an Unusual Alkaloid from the Mangrove Endophytic FungusTalaromycessp. (HZ-YX1) as Inhibitor of Mycobacterial PknG.New Journal of Chemistry, 2017, 146:8-15.Liu Z, Chen S, Qiu P, Tan C, Long Y, Lu Y, She Z. (+)- and (-)-Ascomlactone A: a pair of novel dimeric polyketides from a mangrove endophytic fungusAscomycotasp. SK2YWS-L.Organic & Biomolecular Chemistry. 2017, 15(48):10276-10280.Sun Yunhao, Li Pai, Deng Mengying, Shen Dong, Dai Guangyi, Yao Nan, Lu Yongjun*. TheRalstonia solanacearumeffector RipAK suppresses plant hypersensitive response by inhibiting the activity of host catalases.Cellular Microbiology, 2017, 19: e12736.Dongni Chen, Shuangshuang Ma, Lei He, Peibo Yuan, Zhigang She and Yongjun Lu*. Sclerotiorin inhibits protein kinase G fromMycobacterium tuberculosisand impairs mycobacterial growth in macrophages.Tuberculosis, 2017,103:37-43.Chunbin Tan, Zhaoming Liu, Senhua Chen, Xishan Huang, Hui Cui, Yuhua Long, Yongjun Lu and Zhigang She. Antioxidative Polyketones from the Mangrove-Derived FungusAscomycotasp. SK2YWS-L.Scientific report, 2016 Nov 4;6:36609.Meng-ying Deng, Yun-hao Sun, Pai Li, Bei Fu, Dong Shen, Yong-jun Lu*. The phytopathogenic virulent effector protein RipI induces apoptosis in budding yeastSaccharomyces cerevisiae.Toxicon, 2016, 121:109-118.Bei-bei Zhao, Xiang-hui Li, Yong-lun Zeng and Yong-jun Lu*. ClpP-deletion impairs the virulence of Legionella pneumophila and the optimal translocation of effector proteins.BMC Microbiology, 2016, 16(1):174-185.Hui Cui, Yayue Liu, Yang Nie, Zhaoming Liu, Zhengrui Zhang, Yongjun Lu, Lei He, Xishan Huang *, Zhigang She*. Polyketides from the Mangrove-Derived Endophytic FungusNectriasp. HN001 and Their α-Glucosidase Inhibitory Activity.Marine Drugs,2016, 14(5)：86.Liu, Zhaoming; Chen, Yan; Chen, Senhua; Liu, Yayue; Lu, Yongjun; Chen, Dongni; Lin, Yongcheng; Huang, Xishan; She, Zhigang. Aspterpenacids A and B, Two Sesterterpenoids from a Mangrove Endophytic FungusAspergillus terreusH010.Organic Letters, 2016, 18:1406-1409.Dong-ni Chen, Hong Chen, Zhi-gang She, Yong-jun Lu*. Identification of Bostrycin Derivatives on Inhibition of MptpB Phosphatase fromMycobacterium tuberculosis.Medicinal Chemistry, 2016;12(3):296-302.Li J, Xue YY, Yuan J, Lu YJ, Zhu X, Lin YC, Liu L*. Lasiodiplodins from Mangrove Endophytic FungusLasiodiplodiasp. 318#.Natural Product Research, 2016, 30(7), 755-760.Senhua Chen, Zhaoming Liu, Hanxiang Li, Guoping Xia, Yongjun Lu, Lei He, Shaodong Huang, Zhigang She. β-Resorcylic acid derivatives with a-glucosidase inhibitory activity fromLasiodiplodiasp. ZJ-HQ1, an endophytic fungus in the medicinal plantAcanthus ilicifolius,Phytochem. Lett. 2015,13, 141u2013146.Senhua Chen, Zhaoming Liu, Yayue Liu, Yongjun Lu, Lei He, Zhigang She. New Depsidones and Isoindolones from the Mangrove Endophytic FungusMeyerozyma guilliermondii(HZ-Y2) Isolated from the South China Sea,Beilstein J. Org. Chem.2015,11,1187u20131193.Liu Y, Yang Q, Xia G, Huang H, Li H, Ma L, Lu Y, He L, Xia X, She Z. Polyketides with α-Glucosidase Inhibitory Activity from a Mangrove Endophytic Fungus,Penicilliumsp. HN29-3B1.J Nat Prod. 2015，78(8):1816-22.He Lei, Deng Qing-li, Chen Mou-tong, Wu Qing-ping, Lu Yong-jun*. Proteomics analysis ofListeria monocytogenesATCC 19115 in response to simultaneous triple stresses.Archives of Microbiology, 2015, 197(6):833-841.Yayue Liu, Senhua Chen, Zhaoming Liu, Yongjun Lu, Guoping Xia, Hongju Liu, Lei He and Zhigang She. Bioactive Metabolites from Mangrove Endophytic FungusAspergillussp. 16-5B.Marine Drugs, 2015, 13: 3091-3102.Ze’en Xiao, Shao’e Lin, Chunbin Tan, Yongjun Lu, Lei He, Xishan Huang, Zhigang She. Asperlones A and B, Dinaphthalenone Derivatives from a Mangrove Endophytic FungusAspergillussp. 16-5C.Marine Drugs,2015, 13: 366-378.Sun Meng-yi, Lu Yong-jun*. A simple method for constructing magneticEscherichia coli.BioRxiv, 2014, October 10, doi: http://doi.org /10.1101/ 010249Yayue Liu, Guoping Xia, Hanxiang Li, Lin Ma, Bo Ding , Yongjun Lu , Lei He , Xuekui Xia *, Zhigang She*, Vermistatin Derivatives with α-Glucosidase Inhibitory Activity from the Mangrove Endophytic FungusPenicilliumsp. HN29-3B1.Planta Med., 2014, 80, 912-917.Li Jing，Yang Xin, Lin Yingying, Yuan Jie, Lu Yongjun, Zhu Xun, Li Jun, Li Mengfeng, Lin Yongcheng, He Jianguo, Liu Lan. Meroterpenes and azaphilones from marine mangrove endophytic fungusPenicillium303#.Fitoterapia, 2014, 97:241-246.Guoping Xia, Jia Li, Hanxiang Li, Yuhua Long, Shaou2019e Lin, Yongjun Lu, Lei He, Yongcheng Lin, Lan Liu and Zhigang She. Alterporriol-Type Dimers from the Mangrove Endophytic Fungus,Alternaria sp. (SK11), and Their MptpB Inhibitions.Marine Drugs, 2014, 12：2953-2969.Li HX, Jiang J, Liu Z, Lin S, Xia G, Xia X, Ding B, He L, Lu Y*, She Z*. Peniphenones A-D from the Mangrove FungusPenicillium dipodomyicolaHN4-3A as Inhibitors ofMycobacterium tuberculosisPhosphatase MptpB.J Nat Prod. 2014,77(4): 800?806.Ding B, Yuan J, Huang X, Wen W, Zhu X, Liu Y, Li H, Lu Y, He L, Tan H, She Z. New dimeric members of the phomoxanthone family: phomolacton-exanthones A, B and deacetylphomoxanthone C isolated from the fungusPhomopsissp.Marine Drugs. 2013 , 11(12):4961-72.Du J, Xiao K, Li L, Ding X, Liu H, Lu Y, Zhou S. Temporal and spatial diversity of bacterial communities in coastal waters of the South china sea.PLoS One. 2013, 8(6):e66968.Xiao Z, Huang H, Shao C, Xia X, Ma L, Huang X, Lu Y, Lin Y, Long Y, She Z. Asperterpenols A and B, new sesterterpenoids isolated from a mangrove endophytic fungusAspergillussp. 085242.Organic Letters.2013, 15(10):2522-5.Du J, Li L, Ding X, Hu H, Lu Y, Zhou S. Isolation and characterization of a novel cyanophycin synthetase from a deep-sea sediment metagenomic library.Appl Microbiol Biotechnol.2013, 97(19):8619-28.Huang, Xishan; Huang, Hongbo; Li, Hanxiang; Sun, Xuefeng; Huang, Huarong; Lu, Yongjun; Lin, Yongcheng; Long, Yuhua*; She, Zhigang *. Asperterpenoid A, a New Sesterterpenoid as an Inhibitor ofMycobacterium tuberculosisProtein Tyrosine Phosphatase B from the Culture ofAspergillussp. 16-5c.OrganicLetters. 2013，15（4）：721-723.Huang C, Jin H, Song B, Zhu X, Zhao H, Cai J, Lu Y, Chen B, Lin Y. The cytotoxicity and anticancer mechanisms of alterporriol L, a marine bianthraquinone, against MCF-7 human breast cancer cells.Appl Microbiol Biotechnol. 2012, 93(2):777-85.Ding X, Yin B, Qian L, Zeng Z, Yang Z, Li H, Lu Y, Zhou S. Screening for novel quorum-sensing inhibitors to interfere with the formation ofPseudomonas aeruginosabiofilm.J Med Microbiol. 2011, 60(Pt 12):1827-34.Hanxiang Li, Hongbo Huang, Changlun Shao, Huarong Huang, Jieyi Jiang, Xun Zhu,Yayue Liu Lan Liu,Yongjun Lu, Mengfeng Li, Yongcheng Lin,and Zhigang She. Cytotoxic Norsesquiterpene Peroxides from the Endophytic FungusTalaromyces flavusIsolated from the Mangrove PlantSonneratia apetala.Journal of Natural Products，2011, 74, 1230u20131235.Cai-Huan Huang, Jia-Hui Pan, Bin Chen, Miao Yu, Hong-Bo Huang, Xun Zhu,Yong-Jun Lu, Zhi-Gang She and Yong-Cheng Lin. Three Bianthraquinone Derivatives from the Mangrove Endophytic FungusAlternariasp. ZJ9-6B from the South China Sea.Marine Drugs, 2011, 9(5):832-843.Hongbo Huang, Xiaojun Feng,Zeu2019en Xiao, Lan Liu, Hanxiang Li, Lin Ma, Yongjun Lu, Jianhua Ju, Zhigang She, and Yongcheng Lin. Azaphilones and p-Terphenyls from the Mangrove Endophytic FungusPenicillium chermesinum(ZH4-E2) Isolated from the South China Sea.Journal of Natural Products，2011 74, 997u20131002.Huixian Li, Yali Huang, Jiong Zhang, Jikun Du, Hongming Tan, Yongjun Lu, Shining Zhou. Identification and characterization of a novel methionine c-lyase gene from deep-sea sediment metagenomic library.World J Microbiol Biotechnol, 2011, 27:2729u20132736.Jikun Du, Kai Xiao, Yali Huang, Huixian Li, Hongming Tan, Lixiang Cao, Yongjun Lu ,Shining Zhou. Seasonal and spatial diversity of microbial communities in marine sediments of the South China Sea.Antonie van Leeuwenhoek, 2011,100（3）：317-331.Fenju Lai, Rentian Wu, Jiafeng Wang, Chunming Li, Lan Zou, Yongjun Lu and Chun Liang. Far3p domains involved in the interactions of Far proteins and pheromone-induced cell cycle arrest in budding yeast.FEMS Yeast Research,2011 Feb;11(1):72-9.Lijuan Ma, Yuanliang Zhai, Daorong Feng, Tsz-choi Chan, Yongjun Lu, Xinrong Fu, Jiafeng Wang, Yanhong Chen, Jianna Li, Ke Xu, and Chun Liang. Identification of Novel Factors Involved in or Regulating Initiation of DNA Replication by a Phenotypic Screen inSaccharomyces cerevisiae.Cell Cycle, 2010,9(21):4399-4410.Hong-Bo Huang, Xiao-Jun Feng, Lan Liu, Bin Chen, Yong-Jun Lu, Lin Ma, Zhi-Gang She, Yong-Cheng Lin. Three Dimeric Naphtho-γ-Pyrones from the Mangrove Endophytic FungusAspergillus tubingensisIsolated fromPongamia pinnata.Planta Medica, 2010,76: 1888u20131891Kai-Kai Li, Yong-Jun Lu, Xiao-Hong Song, Zhi-Gang She, Xi-Wei Wu, Lin-Kun An,Chuang-Xing Ye, Yong-Cheng Lin. The metabolites of mangrove endophytic fungus Zh6-B1 from the South China Sea.Bioorganic & Medicinal Chemistry Letters, 2010,20: 3326u20133328.Xiang-hui Li, Yong-lun Zeng, Ye Gao, Xiao-cong Zheng, Qin-fen Zhang, Shi-ning Zhou, Yong-jun Lu*. The ClpP protease homologue is required for the transmission traits and cell division of the pathogenLegionella pneumophila.BMC Microbiology,2010, 10(1):54.Zhen Xu, Xue Cheng, Jiafeng Wang, Yuanliang Zhai, Yongjun Lu and Chun Liang. ATP-Dependent Pre-Replicative ComplexAssembly Is Facilitated by Adk1p in Budding Yeast.J. Biological Chemistry, 2010 ,285(39):29974-80.Jiafeng Wang, Rentian Wu, Yongjun Lu and Chun Liang. Ctf4p Facilitates Mcm10p to Promote Initiation of DNA Replication in Budding Yeast.Biochemical and Biophysical Research Communications, 2010, 395:336u2013341.Chun-ling Xu, Jia-feng Wang, Ye Gao, Huang-yu Lin, Lin Du, Shan-shan Yang, Si-mei Long, Zhi-gang She, Xiao-ling Cai, Shi-ning Zhou, Yong-jun Lu*. The anthracenedione compound bostrycin induces mitochondria-mediated apoptosis in the yeastSaccharomyces cerevisiae.FEMS Yeast Research,2010, 10（3）: 297u2013308.Yiguang Chen, Jiahui Pan, Fan Liu, JianXiang Yang, Caihuan Huang, Xiaolin Cai, Yongjun Lu, Zhigang She and Yongcheng Lin. A new indene derivative from the marine fungusPhomopsissp. (No. GX7-4A).Chem Nat Commpd. 2010,2:1-2.Wen-han Zhu, Lan Luo, Jia-yi Wang, Xiao-hong Zhuang, Ling Zhong, Kang Liao, Yan Zeng, Yong-jun Lu* . Complete nucleotide sequence of pCTX-M360, an intermediate plasmid between pEL60 and pCTX-M3, from a multidrug resistantKlebsiella pneumoniaeisolated in China.Antimicrobial Agents and Chemotherapy, 2009, 53(12):5291-5293Ming-jia Yu, Jun Ren, Yong-lun Zeng, Shi-ning Zhou and Yong-jun Lu*. TheLegionella pneumophilaDps homolog is regulated by iron and involved in multiple stress tolerance.Journal of Basic Microbiology，2009, 49: 1u20138.

二、 主编教材：《生物技术综合实验》, 2017，中山大学出版社，第1版；2019年第二次印刷。