研究组长介绍

路丽明，女，欧洲杯竞猜平台，教授，研究员，博士生导师

基础欧洲杯竞猜平台免疫学与微生物学系课题组长（PI）

欧洲杯竞猜平台附属胸科医院实验中心创始主任

《现代免疫学》杂志执行主编

联系方式：021-63846590-776023

邮箱地址：lulunew2003@163.com

邮编：200025

个人简历

1998年7月毕业于厦门大学，获学士学位。2001年7月和2006年7月毕业于欧洲杯竞猜平台（原上海第二医科大学）医学免疫学专业，获医学硕士和医学博士学位。2013年至2014年英国剑桥大学高级访问学者。

担任上海市免疫遗传学会副主任委员，上海市免疫学会常务理事，中国免疫学会健康委员会常务委员，中华医学生物免疫学会常务理事，中国细胞治疗质控与研究专委会常务委员，中华医学会疫苗接种委员会常务委员，中国病理生理学会实验血液学专业委员会常务委员，教育部学位中心全国博士论文评审专家，国家自然科学基金委评审专家。

研究方向

研究方向为免疫调节，开展移植免疫耐受和肿瘤免疫治疗获益人群的筛选的研究。取得一系列发现和成果。先后主持国家重点基础研究发展计划（973计划）子课题，科技部863项目和国家自然科学基金，上海市重点项目等15项。作为通讯作者和共同作者在本领域列期刊和国际专业期刊等发表论文100余篇，SCI论文50篇，引用近500次。申请或授权国家发明专利6项。

欧洲杯竞猜平台整合教程－机体防御与免疫主讲老师，熟练教授研究生、本科医学免疫学、免疫学技术等课程。《人体健康与免疫》科普丛书《婴幼儿篇》副主编、《常见问题篇》、参编国家新闻出版总署列为“十五”国家重点图书出版规划项目《组织工程学原理与实践》、《免疫学技术》、教育部研究生指定教材《免疫学原理》、《医学免疫学与检验》英文版留学生教材《 Textbook of Immunology》、 《肿瘤免疫学》、《医学免疫学》等规划教材。入选上海市浦江人才计划、上海市曙光学者、上海市科技启明星人才计划、上海市教委骨干教师出国高访计划、上海市卫生系统优青、交大晨星学者、欧洲杯竞猜平台新百人等人才计划。

科研项目

(1) 国家973 重点基础研究项目：单倍型相合移植（“北京方案”）后适应性免疫重建及调控机制（ 2017YFA0104600），主持

(2) 国家自然科学基金项目（ 82071856）: 中药天花粉蛋白作为A群流脑疫苗免疫增效剂的应用基础研究，主持

(3) 国家自然科学基金项目（81671579）: Tk衍生肽通过Treg细胞抑制同种异体肺移植慢性排斥的应用基础研究，主持

(4) 国家自然科学基金项目（ 31370904）: II类反式激活因子通过NLR信号调控Th2应答的分子免疫学机制，主持

(5) 国家自然科学基金青年项目（30700766）: 构建CIITA突变体转基因小鼠功能性剔除MHC及作用机制研究，主持

(6) 国家自然科学基金面上项目（30972691）:天花粉蛋白衍生肽诱导的IL-9+IL-10+T细胞与Th9的免疫生物学特性比较研究，主持

(7) 上海市中医药局面上项目（2020JP009）：组蛋白去甲基化酶LSD1对天花粉蛋白诱导的CD8+Treg谱系维持的作用，主持

(8) 上海市教委(16SG14)：中药天花粉蛋白衍生肽通过Treg细胞延缓肺移植术后闭塞性细支气管炎综合症的可行性研究，主持

(9) 上海市科委基础研究重点项目（11JC1410802）通过诱导调节性T细胞抑制肺移植慢性免疫排斥的应用基础研究，主持

(10) 上海市科委生药研究重点项目（15401900500）：天花粉蛋白有效组分作为免疫调节细胞专一诱导剂的药效学研究，主持

(11) 上海市浦江人才计划项目（15PJD021）生物活性多肽治疗Th1细胞主宰疾病的药效及作用机理研究，主持

(12) 上海市科委产学研项目（14DZ1931003）自体免疫细胞治疗肺癌的医学转化研究，主持

(13) 上海市卫生系统新优青人才培养计划（2011XYQ015）IFN-gR+IL-10R+Tr1细胞的免疫生物学特性及应用基础研究，主持

(14) 上海市教委资助项目（2685619）：mCIITA分子联合B7-H1诱导产生的调节性T细胞的免疫生物学特性研究，主持

(15) 上海市科委实验动物项目（18140903800）肺癌双人源化PDX模型的构建与临床患者药物治疗方案评估的探索，主持

(16) 国家973 重点研发计划项目（ 2020YFA010045）：人脐带间充质干细胞治疗视神经脊髓炎谱系疾病的临床研究，骨干成员

(17) 国家973重点基础研究项目（ 2010CB945600）：组织干细胞的干性维持、分化控制和免疫调节研究，骨干成员

(18) 国家自然科学基金重点项目（ 30530690）： MHC和Th1/Th2分化相关基因转录激活调控的表观遗传学研究，第一参与人

论文与专著

(1) Christopher D Nishimura, Marc C Pulanco, Wei Cui, Liming Lu*, Xingxing Zang PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies. Trends Mol Med.2020 Nov 13;S1471-4914(20)30266-5.

(2) Duo Zhang; Di Tang; Yu Heng; Xiao-Ke Zhu; Liang Zhou; Lei Tao; Li-Ming Lu* Prognostic Impact of Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma Patients. Laryngoscope. 2020 Oct 27. doi: 10.1002/lary.29196.

(3) Zhang Yu; Zhou Lin; Gu Xiang; Feng Xuan; Ding Ping; Xia Qiang; Li-Ming Lu* CXCL8high inflammatory B cells in the peripheral blood of patients with biliary atresia are involved in disease progression. Immunology & Cell Biology. 2020; 1–11

(4) Zhang, Na; Sun, Pan; Jin, Haizhen; Yang, Yuqin; Zhao, Qingya; Zhou, Lin; Guo, Lili; Yang, Xiaohua; Li-Ming Lu* Chidamide combined with paclitaxel effectively reverses the expression of histone deacetylase in lung cancer. Anti-Cancer Drugs. 2020 August; 31(7):702-708,

(5) Yi Xue , Di Tang , Sheng-Jie Li , Jian Zhou , Chi-Yao Hsueh , Dan-Dan Zhao , Yu Heng , Lei Tao, Li-Ming Lu* Link Between CIITA rs3087456 Polymorphism and the Risk of Laryngeal Squamous Cell Carcinoma in a Chinese Population. Pathol Res Pract. 2020 Jan;216(1):152793.

(6) Jian Zhou, Liang Zhou, Duo Zhang, Wei-Jing Tang, Di Tang, Xiao-Ling Shi, Yue Yang, Lin Zhou, Fei Liu, Yong Yu, Pentao Liu, Lei Tao, Li-Ming Lu*. BCL11A promotes the progression of laryngeal squamous cell carcinoma. Frontiers in Oncology. 2020 Mar 20;10:375. doi: 10.3389/fonc.2020.00375

(7) Gao, Xuefei; Nowak-Imialek, Monika; Chen, Xi; Chen, Dongsheng; Herrmann, Doris; Ruan, Degong; Chen, Andy Chun Hang; Eckersley-Maslin, Melanie A; Ahmad, Shakil; Lee, Yin Lau; Kobayashi, Toshihiro; Ryan, David; Zhong, Jixing; Zhu, Jiacheng; Wu, Jian; Lan, Guocheng; Petkov, Stoyan; Yang, Jian; Antunes, Liliana; Campos, Lia S; Fu, Beiyuan; Wang, Shengpeng; Yong, Yu; Wang, Xiaomin; Xue, Song-Guo; Ge, Liangpeng; Liu, Zuohua; Huang, Yong; Nie, Tao; Li, Peng; Wu, Donghai; Pei, Duanqing; Zhang, Yi; Lu, Liming; Yang, Fengtang; Kimber, Susan J; Reik, Wolf; Zou, Xiangang; Shang, Zhouchun; Lai, Liangxue; Surani, Azim; Tam, Patrick P L; Ahmed, Asif; Yeung, William Shu Biu; Teichmann, Sarah A; Niemann, Heiner; Liu, Pentao. Establishment of porcine and human expanded potential stem cells. Nature cell biology, 2019, 21(6): 687. Establishment of porcine and human expanded potential stem cells. Nature cell biology, 2019, 21(6): 687.

(8) Lin Ye, Yuqing Lou, Liming Lu* and Xiaohong Fan. Mesothelin-targeted second generation CAR-T cells inhibit growth of mesothelin-expressing tumors in vivo. Exp Ther Med. 2019 Jan;17(1):739-747.

(9) Yuanyuan Li, Mengyue Niu, Aonan Zhao, Wenyan Kang, Zhichun Chen, Ningdi Luo, Liche Zhou, Xiongwei Zhu, Liming Lu* and Jun Liu*. CXCL12 is involved in α-synuclein-triggered neuroinflammation of Parkinson’s disease. Journal of J Neuroinflammation. 2019;16(1):263.

(10) HeYu-Bin; GuoJiang-Hong; WangChong; Zhu Dan; Lu Li-Ming*. IL-33 promotes the progression of nonrheumatic aortic valve stenosis via inducing differential phenotypic transition in valvular interstitial cells. Journal of cardiology. 2019 Aug 12. [Epub ahead of print]

(11) Yi xue, Huai-Dong Du, Di Tang, Duo Zhang, Jian Zhou, Chang-Wen Zhai, Cun-Cun Yuan, Chi-Yao Hsueh, Sheng-Jie Li, Yu Heng, Lei Tao and Li-ming Lu*. Correlation Between the NLRP3 Inflammasome and the Prognosis of Patients With LSCC. FRONTIERS IN ONCOLOGY , 2019 , Jul 2;9:588

(12) Guo-wei Tu ,Min-jie Ju, Yi-jun zheng, Guang-wei Hao,Guo-guang Ma, Jun-yi Hou, Xue-peng Zhang, Zhe Luo, Li-ming Lu*. CXCL16/CXCR6 Is Involved in LPS-induced Acute Lung Injury via P38 Signaling. Cell Physiol Biochem. 2019; 00; 1-10

(13) Jun Lu, Hua Zhong, Tianqing Chu, Xueyan Zhang, Rong Li, Jiayuan Sun, Runbo Zhong, Yuqin Yang, Mohammad Shah Alam, Yuqing Lou, Jianlin Xu, Yanwei Zhang, Jun Wu, Xiaowei Li, Xiaodong Zhao, Kai Li, Liming Lu*, Baohui Han. Role of anlotinib-induced CCL2 decrease in anti-angiogenesis and response prediction for non-small cell lung cancer therapy. European Respiratory Journal . 2019 Mar 1;53(3). pii: 1801562. doi: 10.1183/13993003.01562-2018

(14) Weimin Fan, Yali Xu, Yue Liu , Zhengqing Zhang , Liming Lu* and Zhide Ding，Obesity or Overweight, a Chronic Inflammatory Status in Male Reproductive System, Leads to Mice and Human Subfertility. Frontiers in Physiology, 2018, 8:1117. doi: 10.3389/fphys.

(15) Xiaoyan Yu, Yimin Lao, Xiao-Lu Teng, Song Li, Yan Zhou, Feixiang Wang, Xinwei Guo, Siyu Deng, Yuzhou Chang, Xuefeng Wu, Zhiduo Liu, Lei Chen, Liming Lu, Jinke Cheng, Bin Li, Bing Su, Jin Jiang, Hua-Bing Li, Chuanxin Huang, Jing Yi & Qiang Zou . SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation[J]. Nature communications, 2018, 9(1): 3157. DOI: 10.1038/s41467-018-05676-6

(16) Xiaoyan Yu, XiaoLu Teng, Feixiang Wang, Yuhan Zheng, Guojun Qu, Yan Zhou, Zhilin Hu, Zhongqiu Wu, Yuzhou Chang, Lei Chen,HuaBing Li, Bing Su, Liming Lu*, Zhiduo Liu, ShaoCong Sun, and Qiang Zou. Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome. J Exp Med . 2018 Sep 3;215(9):2463-2476. doi: 10.1084/jem.20180397

(17) Yue Wang, Qing Li, Lin Zhou, Xueping Ding, Li-ming Lu*. Peptede TK-PQ induces immunosuppression in skin allogeneic transplantation via increasing Foxp3+ Treg and impeding nuclear translocation of NF-κB. Molecular Immunology. 2018 Sep;101:597-607. doi: 10.1016/j.molimm.

(18) Xiao-yang Zhang, Lin Zhou, Zhen Guo, Ye Kong, Wei Zhang, Li-ming Lu*，Xin Li*, Regulatory T Cells may Play an Protection Role in Lung Injury after Operation in Rheumatic Heart Disease. Journal of Thoracic Disease, 2018 Jun;10(6):3196-3205. doi: 10.21037/jtd.2018.05.71

(19) ZongAn Chen*, Lin Zhou*, TaeHao Won, Zhen Gao, XiaoLi Wu and Li-ming Lu*。Characterization of Memory T Lymphocytes in Keloid Disease. Br J Dermatol. 2018 Apr;178(4):940-950. doi: 10.1111/bjd.16173.

(20) Yang Jian,Ryan David J,Wang Wei, Jason Cheuk-Ho Tsang, Guocheng Lan, Hideki Masaki, Xuefei Gao, Liliana Antunes, Yong Yu, Zhexin Zhu, Juexuan Wang, Aleksandra A. Kolodziejczyk, Lia S. Campos, Cui Wang, Fengtang Yang, Zhen Zhong, Beiyuan Fu, Melanie A. Eckersley-Maslin, Michael Woods, Yosuke Tanaka, Xi Chen, Adam C. Wilkinson, James Bussell, Jacqui White, Ramiro Ramirez-Solis, Wolf Reik, Berthold Göttgens, Sarah A. Teichmann, Patrick P. L. Tam, Hiromitsu Nakauchi, Xiangang Zou, Liming Lu & Pentao Liu*. Establishment of mouse expanded potential stem cells.[J] .Nature, 2017, 550(7676): 393-397.

(21) Zhang D, Zhou J, Tang D, Lei Tao, Lu L*. Neutrophil infiltration mediated by CXCL5 accumulation in the laryngeal squamous cell carcinoma microenvironment: A mechanism by which tumour cells escape immune surveillance. Clinical Immunology, 2017, 175: 34-40.

(22) Tang Wei-Jing,Tao Lei, Li-ming Lu* et al. Role of T helper 17 cytokines in the tumour immune inflammation response of patients with laryngeal squamous cell carcinoma.[J] .Oncol Lett, 2017, 14(1): 561-568.

(23) Zhou, J., Yang, Y., Zhang, D., Zhou, L., Tao, L., & Lu L*. Genetic polymorphisms and plasma levels of BCL11A contribute to the development of laryngeal squamous cell carcinoma. PloS one, 2017 Feb 22;12(2):e0171116.

(24) Yu, Y, Tsang, C-H. J, Wang, C, Simon Clare, Juexuan Wang,Xi Chen, CordeliaBrandt, Leanne Kane, Lia S. Campos, Lu Lu*, Gabrielle T. Belz, Andrew N. J. McKenzie,Sarah A.Teichmann, Gordon Dougan& Pentao Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its developmental pathway. Nature. 2016 Sep; 539(7627)

(25) Li Z, Yang N, Zhou L, Lu L*, Chou KY. A peptide tetramer Tk-tPN induces tolerance of cardiac allografting by conversion of type 1 to type 2 immune responses via the Toll‐like receptor 2 signal‐promoted activation of the MCP1 gene. Immunology, 2016, 147(3): 355-366.

(26) Tang, D, W. J. Tang, X. L. Shi, W. P. Li, H. Zhou, Lu L*, L. Tao Association of the microsatellite (GT)n repeat polymorphisms of the HO-1 gene promoter and corresponding serum levels with the risk of laryngeal squamous cell carcinoma. Acta Otolaryngol, 2016. 136, 806-11.

(27) Zhang, D, W. J. Tang, D. Tang, J. Zhou, L. Chou, L. Tao &Lu L* The ratio of CD4/CD8 T-cells in human papillomavirus-positive laryngeal squamous cell carcinoma accounts for improved outcome. Acta Otolaryngol, 2016.136, 826-33.

(28) Zhou, J, Y. Yang, D. Zhang, L. Zhou, F. Liu, L. Tao, Lu L* Association of the recurrence of vocal leukoplakia with MDM2-309 variants over a 2-year period: a prospective study. Acta Otolaryngol, 2016.136, 95-9.

(29) ZhouJ, D.Zhang, L. Zhou, Y. Yang, F. Liu, L. Tao, Lu L* Association of the recurrence and canceration rate of vocal leukoplakia with interleukin-10 promoter variants over a 2-year period. Acta Otolaryngol, 2016. 136, 1147-1153.

(30) Zhang D, Chen B, Zhou J, Zhou L, Li Q, Liu F, Chou KY, Tao L, Lu L*. Low concentration of Trichosanthin induces apoptosis and cell cycle arrest through JNK/MAPK activation. Molecular Medicine Report. 2015 Jan;11(1):349-56. doi: 10.3892/mmr

(31) Zhou J, Yang Y, Zhang D, Zhou L, Liu F, Tao L, Lu L*. Association of the recurrence of vocal leukoplakia with MDM2-309 variants over a 2-year period: a prospective study. Acta oto-laryngologica 2015:1-5.

(32) Yu Y, Wang C, Clare S, Wang J, Lee SC, Brandt C, Burke S1, Lu L*, He D, Jenkins NA, Copeland NG, Dougan G, Liu P.. The transcription factor Bcl11b is specifically expressed in group 2 innate lymphoid cells and is essential for their development. The Journal of experimental medicine 2015; 212:865-74.

(33) Tsang JC, Yu Y, Burke S, Buettner F, Wang C, Kolodziejczyk , Teichmann SA, Lu L*, Liu P, Single-cell transcriptomic reconstruction reveals cell cycle and multi-lineage differentiation defects in Bcl11a-deficient hematopoietic stem cells. Genome Biol. 2015 Sep 21;16(1):178. doi:10.1186/s13059-015-0739-5.

(34) Yang J, Wang W, Ooi J, Campos LS, Lu L*, Liu P Signalling Through Retinoic Acid Receptors is Required for Reprogramming of Both Mouse Embryonic Fibroblast Cells and Epiblast Stem Cells to Induced Pluripotent Stem Cells. Stem Cells. 2015 May 33(5):1390-404. doi: 10.1002/stem.1926

(35) Zhao AM, Xu HJ, Kang XM, Zhao AM, Lu. L* .New insights into myeloid-derived suppressor cells and their roles in feto-maternal immune cross-talk. J Reprod Immunol. 2015 Nov 10;113:35-41. doi: 10.1016/j.jri.2015.11.001.

(36) Xuefei Gao, Jason C.H. Tsang, Fortis Gaba, Donghai Wu, Lu L*, Pentao Liu Comparison of TALE designer transcription factors and the CRISPR/dCas9 in regulation of gene expression by targeting enhancers. Nucleic Acids Research, 2014 doi: 10.1093/nar/gku836

(37) Tsang JC, Xuefei Gao, Lu. L*, Pentao Liu Cellular reprogramming by transcription factor engineering. Current Opinion in Genetics & Development 2014, 28:1–9

(38) Jian Zhou, Duo Zhang, Bin Chen, Qing Li, Lin Zhou, Fei Liu, Kuang-Yen Chou, Lei Tao, Lu L*. Association of interleukin 10 promoter polymorphisms and corresponding plasma levels with susceptibility to laryngeal squamous cell carcinoma ONCOLOGY LETTERS 2014,7: 1721-1727.

(39) F. Liu, X. Pan, L. Zhou, B. Chen, J. Shi, W. Gao and Lu. L*. Genetic polymorphism and plasma levels of interleukin-22 contribute to the development of nonsmall lung cancer. DNA and CellBiology. 2014 Oct;33(10):705-14. doi: 10.1089/dna.

(40) Zhou J, Liu F, Zhang D, Chen B, Li Q, Zhou L, Lu L*, Tao L. Significance of MDM2-309 polymorphisms and induced c orresponding plasma MDM2 levels in susceptibility to laryngeal squamous cell carcinoma DNA Cell Biol. 2014 Feb;33(2):88-94.

(41) Neng Yang, Zuoqing Li, Zhijun Jiao, Peng Gu, Yun Zhou, Lu.L*, Kuang-Yen Chou A Trichosanthin-derived peptide suppresses type 1 immune responses by TLR2-dependent activation of CD8+CD28−Tregs Clinic immunology (2013), 153, 277–287.

(42) Bin Chen, Duo Zhang, Jian Zhou, Qing Li, Lin Zhou, Shi-Min Li, Li Zhu, Kuang-Yen Chou, Liang Zhou, Lei Tao, Lu L*, High CCR6/CCR7 expression and Foxp3+ Treg cell number are positively related to the progression of laryngeal squamous cell carcinoma. ONCOLOGY REPORTS 2013 30: 1380-1390.

(43) Yang ZQ, Yang N, Zhou Y, Xin LJ, Lu L*, Chou KY. Mutated MHC class II transactivator upregulates IL-33-dependent differentiation of Th2 subset through Nod2 binding for NLR signaling initiation. Journal of Biological Chemistry, 2012 Mar 23;287(13) :9972-9981

(44) Liu Y, Qu F, Cao X, Chen G, Guo Q, Ying X, Guo W, Lu L*, Ding Z. Con A-binding protein Zn uption of promoter binding with CBP/p300, STAT6 and NFAT1 via histone ered International Journal of Andrology. 2012 Apr;35(2):145-157

(45) Ding Q, Lu L, Xiaorong Zhou, Zhou Y, Chou KY. Human PD-L1-overexpressing porcine vascular endothelial cells induce functionally suppressive human CD4+CD25hiFoxp3+ Treg cells. Journal ofLeukocyte Biology , 2011 Jul, 90 (1):77-86. Co-first author

(46) Wang B, Jiao Z, Shao X, Lu L, Yang N, Zhou X, Xin L, Zhou Y, Chou KY. Phenotypic alterations of dendritic cells are involved in suppressive activity of trichosanthin-induced CD8+CD28- regulatory T cells. Journal of Immunology. 2010 Jul 1: 185(1):79-88

(47) Zhou XR, Zhou Y, Ding Q, Lu L, Yang N, Chou KY. High level expression of B7H1 molecules by keratinocytes suppresses xeno- and allo- eactions by inducing type I regulatory T cells TransplantImmunology, 2009, 21: 192-197

(48) Zhou XR, Yang N, Lu L, Ding Q, Jiao ZJ, Zhou Y, Chou KY. Up-regulation of IL-10 expression in dendritic cells is involved in Trichosanthin-induced immuno- suppression. Immunol Let 2007, 74-81.

(49) Xiaorong Zhou,YangJiang, Lu L, Qing Ding,Kuang-Yen Chou.MHC class II transactivator represses human IL-4 gene transcription by interruption of promoter binding with CBP/p300, STAT6 and NFAT1 via histone hypoacetylation. Immunol, 2007,122,476-485.

(50) Ding Q，Lu L, Wang BL, Zhou Y, Chou KY. B7H1-Ig fusion protein activates the CD4+IFNreceptor+ type 1 T regulatory subset through IFN--secreting Th1 cells. Journal of Immunology, 2006,177： 3606-14. Co-first author

专利与技术许可

2007 Trichosanthin derived peptide and its application, Application Number: 200710173408.94.

2012 Screen of immunosuppressive effective epitope peptide of trichosanthin, Application Number: 201210390572.6.

2016 Application of Trichosanthin in enhancing vaccine specific antibodies, Application Number: 201610049358.2.

2017 PHPO Application for treating lung cancer, Application Number: 201710373254.1.

2020 Construction and application ofa Chinese lung adenocarcinoma cell line, Application Number: 201710426801.8.

团队介绍

本课题组成员目前有课题组长路丽明，技术员丁旭苹、侯亚菲，博士二年级学生王雪，硕士一年级学生吴谦，在路老师的带领下潜心从事免疫调节方面的工作（肿瘤免疫、移植免疫耐受诱导等）， 组内科研助理、学生等各成员间团结协作，密切交流，营造了和谐的科研气氛。同时我们与仁济医院、耳鼻喉医院、同仁医院、胸科医院等临床教学医院开展长期合作，已联合培养学生数名。