基本信息

肖晖 男 博导 上海巴斯德研究所
电子邮件:huixiao@ips.ac.cn
通信地址:上海市岳阳路320号新生命科学研究大楼B楼211
邮政编码:200031
研究领域
TLR、CLR和RLR等天然免疫受体,既可以识别微生物携带的“模式分子”,启动免疫反应、实施宿主防御,也可以识别坏死细胞分泌的“损伤分子”,参与损伤修复、维持机体稳态。感受到病菌入侵或组织损伤后,TLR、CLR、RLR和cGAS/STING等“模式识别受体”通过复杂的信号分子网络,诱导上千种基因表达,参与炎症反应、免疫调节和组织重建等多种生理过程。但是当这些模式识别信号缺陷或失调时,则会导致慢性感染、炎症和肿瘤等疾病。
我们实验室主要研究方向是阐明模式识别受体信号的转导与调节机制,特别是天然免疫信号在DC细胞中介导T细胞亚群分化,调节免疫应答和免疫耐受的分子机制。最近我们通过一系列筛选发现了在TLR、CLR、RLR和cGAS/STING等天然免疫信号通路中分别起正、负调节作用的一些新分子。结合病人资源和动物模型,揭示了这些分子在天然免疫细胞(特别是树突细胞和巨噬细胞)和上皮细胞中调节细胞因子和干扰素表达,影响细胞代谢和细胞死亡的信号转导和表观遗传学机制。接下来我们将重点研究“模式识别受体”如何区分病原体、共生菌和癌变细胞,以启动合适的T细胞免疫反应的分子和细胞学机制,为研发抵御病菌感染、防治炎症和肿瘤的新策略提供理论依据。
招生信息
招生专业
071005-微生物学
071009-细胞生物学
083100-生物医学工程
071009-细胞生物学
083100-生物医学工程
招生方向
探究TLR介导的天然免疫在抗感染中的作用以及新型佐剂的研发TLR信号调节免疫反应的分子和细胞学机理针对自身免疫性疾病和肿瘤的新型药物研发
教育背景
1994-09--1997-07 中国科学院上海植物生理研究所 分子遗传学博士1991-09--1994-07 武汉大学生命科学学院 微生物与免疫学硕士1987-09--1991-07 武汉大学生命科学学院 微生物与免疫学学士
学历
-- 研究生
学位
-- 博士
教授课程
病毒学高级免疫学与病毒学系列讲座天然免疫学生物学进展论坛
专利与奖励
奖励信息
(1) 中科院优秀博士论文指导教师, 研究所(学校), 2017(2) 最佳青年科学家奖, 特等奖, 其他, 2006
出版信息
发表论文
(1) Transfer of cGAMP into Bystander Cells via LRRC8 Volume-Regulated Anion Channels Augments STING-Mediated Interferon Responses and Anti-viral Immunity, Immunity, 2020, 通讯作者(2) Gut epithelial TSC1/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer, The Journal of Clinc Investigation, 2020, 通讯作者(3) A small secreted protein triggers a TLR2/4- dependent inflammatory response during invasive Candida albicans infection, Nature Communications, 2019, 通讯作者(4) Excessive CD11c+Tbet+ B cells promote aberrant TFH differentiation and affinity-based germinal center selection in lupus, Proc Natl Acad Sci U S A., 2019, 其他(合作组作者)(5) TSC1/mTOR-controlled metabolic-epigenetic cross talk underpins DC control of CD8+ T-cell homeostasis, PLoS Biology, 2019, 通讯作者(6) MLL5 suppresses antiviral innate immune response by facilitating STUB1-mediated RIG-I degradation, Nat Commun, 2018, 第 9 作者(7) Elevated sodium chloride drives type I interferon signaling in macrophages and increases antiviral resistance, J Biol Chem, 2018, 其他(合作组作者)(8) The chromatin remodeling subunit Baf200 promotes normal hematopoiesis and inhibits leukemogenesis, J Hematol Oncol, 2018, 其他(合作组作者)(9) Wip1 正调控 TLR4 信号介导的 I 型干扰素表达, 安徽农业大学学报, 2017, 通讯作者(10) NCoR1 restrains thymic negative selection by repressing Bim expression to spare thymocytes undergoing positive selection, Nat Commun, 2017, 其他(合作组作者)(11) Epigenetic regulator CXXC5 recruits DNA demethylase Tet2 to regulate TLR7/9-elicited IFN response in pDCs, The Journal of Experimental Medicine, 2017, 通讯作者(12) 逆转录病毒感染小鼠原代巨噬细胞方法研究, 安徽农业大学学报, 2016, 通讯作者(13) Cross reactivity of S. aureus to murine cytokine assays: A source of discrepancy, Cytokine, 2016, 第 5 作者(14) Fibroblast growth factor 21 improves hepatic insulin sensitivity by inhibiting mammalian target of rapamycin complex 1, hepatology, 2016, 第 10 作者(15) TLR signalling affects sperm mitochondrial function and motility via phosphatidylinositol 3-kinase and glycogen synthase kinase-3α, Cellular Signalling, 2016, 第 7 作者(16) Non-Classical MHC I-E negatively regulates macrophage activation and Th17 cells in NOD mice, scientific reports, 2015, 通讯作者(17) mTOR regulates TLR-induced c-fos and Th1 responses to HBV and HCV vaccines, Virologica Sinica, 2015, 通讯作者(18) Tyrosine phosphatase SHP-2 mediates C-type lectin receptor-induced activation of the kinase Syk and anti-fungal TH17 responses, Nature Immunol, 2015, 通讯作者(19) Casein Kinase II Controls TBK1/IRF3 Activation in IFN Response against Viral Infection., J Immunol, 2015, 通讯作者(20) 骨髓来源巨噬细胞中有效地敲除floxed基因的新方案, 安徽农业大学学报, 2015, 通讯作者(21) Kaposi‘s sarcoma associated herpesvirus-encoded replication and transcription activator impairs innate immunity via ubiquitin-mediated degradation of myeloid differentiation factor 88, J Virol, 2015, 第 6 作者(22) MAPK Phosphatase 5 Expression Induced by Influenza and Other RNA Virus Infection Negatively Regulates IRF3 Activation and Type I Interferon Response, Cell Rep, 2015, 第 9 作者(23) The psoriasis-associated D10N variant of the adaptor Act1 with impaired regulation by the molecular chaperone hsp90, Nature Immunology, 2013, 第 10 作者(24) Inactivation of the Enzyme GSK3 alpha by the Kinase IKKi Promotes AKT-mTOR Signaling Pathway that Mediates Interleukin-1-Induced Th17 Cell Maintenance, IMMUNITY, 2012, 第 3 作者(25) Beta-TrCP-Mediated IRAK1 Degradation Releases TAK1-TRAF6 from the Membrane to the Cytosol for TAK1-Dependent NF-kappa B Activation, MOLECULAR AND CELLULAR BIOLOGY, 2012, 第 3 作者(26) Pellino 2 is critical for Toll-like receptor/interleukin-1 receptor (TLR/IL-1R)-mediated post-transcriptional control, J Biol Chem, 2012, 第 8 作者(27) A novel method for determining microflora composition using dynamic phylogenetic analysis of 16S ribosomal RNA deep sequencing data, Genomics, 2011, 第 4 作者(28) The Kinase Activity of Interleukin-1 Receptor-Associated Kinase 2 Is Essential for Lipopolysaccharide-Mediated Cytokine and Chemokine mRNA Stability and Translation, JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2011, 第 5 作者(29) Loss of single immunoglobulin interlukin-1 receptor-related molecule leads to enhanced colonic polyposis in Apcmin mice, Gastroenterology, 2010, 第 1 作者(30) The receptor SIGIRR suppresses Th17 cell proliferation via inhibition of the interleukin-1 receptor pathway and mTOR kinase activation, Immunity, 2010, 第 8 作者(31) IRAK2 is critical for LPS-mediated post-transcriptional control., Journal of Biological Chemistry, 2009, 第 1 作者(32) The kinase activity of IRAK4 is required for TLR-IL-1R-induced TAK1-dependent NFB activation, J Biol Chem, 2008, 第 3 作者(33) Pellino 3b negatively regulates IL-1-induced TAK1-dependent NF?B activation. , Journal of Biological Chemistry, 2008, 第 1 作者(34) Pyogenic bacterial infections in humans with MyD88 deficiency., Science, 2008, 第 5 作者(35) The Toll-Interleukin-1 receptor member SIGIRR regulates colonic epithelia homeostasis, inflammation and tumorigenesis, Immunity, 2007, 第 1 作者(36) A critical role for IRAK4 kinase activity in Toll-like receptor-mediated innate immunity., J Exp Med, 2007, 第 8 作者(37) Interleukin-1 (IL-1)-induced TAK1-dependent Versus MEKK3-dependent NFB activation pathways bifurcate at IRAK modification, J Biol Chem, 2007, 第 6 作者(38) TLR8-mediated NFB and JNK activation are TAK1-independent and MEKK3-dependent., J Biol Chem, 2006, 第 4 作者(39) Tip60 is a co-repressor for STAT3, J Biol Chem, 2003, 第 1 作者(40) Specificity of IL-2 receptor gamma chain superfamily cytokines is mediated by insulin receptor substrate-dependent pathway, J Biol Chem, 2002, 第 1 作者(41) NifL, an antagonistic regulator of NifA, directly interacts with transcription activator NifA and NtrC, Science in China, 1998, 第 1 作者(42) The Binding site and model of transcription activator SyrM to nodD3 promoter region, Science in China, 1998, 第 1 作者
发表著作
(1) toll样受体信号通路,Signaling by Toll-Like Receptors,Taylor and Francis Group, LLC,2008-07,第1作者
(2) 近代微生物学进展,progresses in morden microbiology,武汉大学出版社,1994-07,第1作者
(2) 近代微生物学进展,progresses in morden microbiology,武汉大学出版社,1994-07,第1作者
指导学生
已指导学生
刘晶华 02 63228
邓子厚 01 19178
现指导学生
谢亚栋 01 19178
周纯 01 19178
王青青 02 63228
何丽 01 19178
赵亦帆 02 19178