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熊思东实验室
 

课题组负责人

熊思东 博士

苏州大学特聘教授

生物医学研究院院长

苏州大学 校长

熊思东教授,1992年在复旦大学(原上海医科大学)获医学博士学位后,曾在法国国立卫生与健康研究院(INSERM)、美国加州大学(UCSD)作博士后和访问学者。曾任复旦大学研究生院副院长、复旦学院院长、免疫生物学研究所所长、上海基因免疫与疫苗研究中心主任、卫生部分子病毒学重点实验室副主任。熊思东教授2009年加盟苏州大学,被聘为特聘教授,同时任苏州大学副校长、苏州大学生物医学研究院院长,现任苏州大学校长。熊思东教授的学术兴趣为分子免疫学和病毒学研究,作为课题负责人主持了国家自然基金重大项目、国家十二五十一五传染病重大专项、国家863项目、国家973子课题、上海市重大项目、上海市科委重点项目、江苏省攀登计划项目、江苏省自然基金重大项目等项目的研究。先后在Nature BiotechnologyPNASHepatologyJ VirolJ ImmunolFaseb JCell Death Differ等学术期刊等发表论文300余篇,申请国家发明专利32项,主编、副主编学术专著14本,参编教材22部。同时曾作为创院院长创建了我国第一个本科生院意义的复旦学院,开国内通识教育之先河,在国内外教育界引起广泛反响。

研究方向

1、感染免疫

感染免疫是研究宿主和病原微生物相互作用的科学,研究病原微生物的免疫逃避和宿主防卫是该领域的方向之一。一方面人类通过固有和获得性免疫系统来抵抗外界微生物的入侵,而另外一个方面病原微生物可能在共同进化过程中利用这个系统来繁殖后代。我们聚焦于柯萨奇病毒B3、乙型肝炎病毒和分支结核杆菌这三类在我国引起重要公共健康问题的病原体进行研究。研究内容包括:动物感染模型的建立、鉴定病原体毒力因子或宿主感受器、分子病理机制研究、新型黏膜疫苗或者治疗策略的设计等。通过这些研究我们期望能够更好的阐述感染性疾病的致病病理机制,同时提供有效的治疗手段。

2、自身免疫性疾病

自身免疫是指机体因未能识别自我构成成分而引起的对自身內源分子,细胞和组织产生的免疫反应。而由此产生的异常免疫应答则会导致自身免疫性疾病。系统性红斑狼疮(SLE)是一种复杂的自身免疫病。病人对自身细胞核内的某些抗原失去免疫耐受,产生致病性的自身抗体,形成抗原-抗体免疫复合物,在多个器官中沉积并导致损伤。该病的病因涉及多种遗传和环境因素,具有很高的多样性。全基因组相关性研究和动物模型,临床数据表明,SLE的病因主要和以下三种免疫途径相关:1、细胞碎片和免疫复合体的清除;2、固有免疫的激活(TLR IIFN介导的炎症反应);3T/B淋巴细胞的激活(过量的淋巴细胞克隆扩增及B细胞免疫耐受缺陷)。当前SLE的研究热点包括免疫反应的细胞调控机制;表观遗传因素和微小RNA对红斑狼疮易感基因表达的调控;筛选能够反映疾病预测及预后风险的的高敏感高特异性生物标志物;及特异性的治疗方法。

代表性论文

1. Zhang H, Yue Y, Sun T, Wu X, Xiong S. Transmissible endoplasmic reticulum stress from myocardiocytes to macrophages is pivotal for the pathogenesis of CVB3-induced viral myocarditis. Scientific reports. Feb 08 2017;7:42162.

2. Qi X, Xiong S. Intein-mediated backbone cyclization of VP1 protein enhanced protection of CVB3-induced viral myocarditis. Scientific reports. Feb 02 2017;7:41485.

3. Fan X, Yue Y, Xiong S. Incorporation of a bi-functional protein FimH enhances the immunoprotection of chitosan-pVP1 vaccine against coxsackievirus B3-induced myocarditis. Antiviral research. Jan 28 2017;140:121-132.

4. He X, Gao B, Zhou L, Xiong S. Green Tea Polyphenol Epigallocatechin-3-gallate-Alleviated Coxsackievirus B3-induced Myocarditis Through Inhibiting Viral Replication but Not Through Inhibiting Inflammatory Responses. Journal of cardiovascular pharmacology. Jan 2017;69(1):41-47.

5. Wang C, Dong C, Xiong S. IL-33 enhances macrophage M2 polarization and protects mice from CVB3-induced viral myocarditis. Journal of molecular and cellular cardiology. Dec 29 2016;103:22-30.

6. Dong N, Dong C, Xiong S. Janus effects of ADAR1 on CVB3-induced viral myocarditis at different infection stages. International journal of cardiology. Nov 15 2016;223:898-905.

7. Zhang M, Dong C, Xiong S. Heterologous boosting with recombinant VSV-846 in BCG-primed mice confers improved protection against Mycobacterium infection. Human vaccines & immunotherapeutics. Dec 14 2016:0.

8. Su N, Yue Y, Xiong S. Monocytic myeloid-derived suppressor cells from females, but not males, alleviate CVB3-induced myocarditis by increasing regulatory and CD4(+)IL-10(+) T cells. Scientific reports. 2016;6:22658.

9. Shi X, Chen Z, Tang S, Wu F, Xiong S, Dong C. Coxsackievirus B3 infection induces autophagic flux, and autophagosomes are critical for efficient viral replication. Archives of virology. Aug 2016;161(8):2197-2205.

10. Ren XX, Wang HB, Li C, Jiang JF, Xiong SD, Jin X, Wu L, Wang JH. HIV-1 Nef-associated Factor 1 Enhances Viral Production by Interacting with CRM1 to Promote Nuclear Export of Unspliced HIV-1 gag mRNA. The Journal of biological chemistry. Feb 26 2016;291(9):4580-4588.

11. Lu M, Xu W, Gao B, Xiong S. Blunting Autoantigen-induced FOXO3a Protein Phosphorylation and Degradation Is a Novel Pathway of Glucocorticoids for the Treatment of Systemic Lupus Erythematosus. The Journal of biological chemistry.Sep 16 2016;291(38):19900-19912.

12. Li F, Gao B, Xu W, Chen L, Xiong S. The Defect in Autophagy Induction by Clinical Isolates of Mycobacterium Tuberculosis Is Correlated with Poor Tuberculosis Outcomes. PloS one. 2016;11(1):e0147810.

13.Zhou L, He X, Gao B, Xiong S. Inhibition of Histone Deacetylase Activity Aggravates Coxsackievirus B3-Induced Myocarditis by Promoting Viral Replication and Myocardial Apoptosis. Journal of virology. Oct 2015;89(20):10512-10523.

14. Zhong L, Hu J, Shu W, Gao B, Xiong S. Epigallocatechin-3-gallate opposes HBV-induced incomplete autophagy by enhancing lysosomal acidification, which is unfavorable for HBV replication. Cell death & disease. 2015;6:e1770.

15. Zhang R, Wang K, Ping X, Yu W, Qian Z, Xiong S#, Sun B#. The ns12.9 Accessory Protein of Human Coronavirus OC43 Is a Viroporin Involved in Virion Morphogenesis and Pathogenesis. Journal of virology. Nov 15 2015;89(22):11383-11395.

16.Zha X, Yue Y, Dong N, Xiong S. Endoplasmic Reticulum Stress Aggravates Viral Myocarditis by Raising Inflammation Through the IRE1-Associated NF-kappaB Pathway. The Canadian journal of cardiology. Aug 2015;31(8):1032-1040.

17. Xuan W, Qu Q, Zheng B, Xiong S, Fan GH. The chemotaxis of M1 and M2 macrophages is regulated by different chemokines. Journal of leukocyte biology. Jan 2015;97(1):61-69.

18. Xu G, Liu G, Xiong S, Liu H, Chen X, Zheng B. The histone methyltransferase Smyd2 is a negative regulator of macrophage activation by suppressing interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) production. The Journal of biological chemistry. Feb 27 2015;290(9):5414-5423.

19. Song T, Dong C, Xiong S. Signaling lymphocyte-activation molecule SLAMF1 augments mycobacteria BCG-induced inflammatory response and facilitates bacterial clearance. International journal of medical microbiology : IJMM. Jul 30 2015.

20. Ren XX, Li C, Xiong SD, Huang Z, Wang JH, Wang HB. Antibodies to P-selectin glycoprotein ligand-1 block dendritic cell-mediated enterovirus 71 transmission and prevent virus-induced cells death. Virulence. Nov 17 2015;6(8):802-808.

21. Qi X, Sun Y, Xiong S. A single freeze-thawing cycle for highly efficient solubilization of inclusion body proteins and its refolding into bioactive form. Microbial cell factories. 2015;14:24.

22. Lu M, Yu S, Xu W, Gao B, Xiong S. HMGB1 Promotes Systemic Lupus Erythematosus by Enhancing Macrophage Inflammatory Response. Journal of immunology research. 2015;2015:946748.

23.Li X, Yue Y, Zhu Y, Xiong S. Extracellular, but not intracellular HMGB1, facilitates self-DNA induced macrophage activation via promoting DNA accumulation in endosomes and contributes to the pathogenesis of lupus nephritis. Molecular immunology. May 2015;65(1):177-188.

24. He L, Zang A, Du M, Ma D, Yuan C, Zhou C, Mu J, Shi H, Li D, Huang X, Deng Q, Xiao J, Yan H, Hui L, Lan K, Xiong S, Li X, Huang Z, Xiao H. mTOR regulates TLR-induced c-fos and Th1 responses to HBV and HCV vaccines. Virologica Sinica. Jun 2015;30(3):174-189.

25. Gui J, Chen R, Xu W, Xiong S. Remission of CVB3-induced myocarditis with Astragaloside IV treatment requires A20 (TNFAIP3) up-regulation. Journal of cellular and molecular medicine. Apr 2015;19(4):850-864.

26. Dong C, Qu L, Wang H, Wei L, Dong Y, Xiong S. Targeting hepatitis B virus cccDNA by CRISPR/Cas9 nuclease efficiently inhibits viral replication. Antiviral research. Jun 2015;118:110-117.

27. Ding L, Gu H, Gao X, Xiong S, Zheng B. Aurora kinase a regulates m1 macrophage polarization and plays a role in experimental autoimmune encephalomyelitis. Inflammation. Apr 2015;38(2):800-811.

28. Chai D, Yue Y, Xu W, Dong C, Xiong S. AIM2 co-immunization favors specific multifunctional CD8(+) T cell induction and ameliorates coxsackievirus B3-induced chronic myocarditis. Antiviral research. Jul 2015;119:68-77.

29. Chai D, Yue Y, Xu W, Dong C, Xiong S: Mucosalco-immunization with AIM2 enhances protective SIgA response and increasesprophylactic efficacy of chitosan-DNA vaccine against coxsackievirus B3-inducedmyocarditis. Human vaccines & immunotherapeutics 2014, 10(5):1284-94.

30. Hu Y, Dong C, Yue Y, Xiong S: In vivo delivery ofinterleukin-35 relieves coxsackievirus-B3-induced viral myocarditis byinhibiting Th17 cells. Archives of virology 2014, 159(9):2411-9.

31. Wen Z, Xu L, Xu W, Xiong S: Detection of dynamicfrequencies of Th17 cells and their associations with clinical parameters inpatients with systemic lupus erythematosus receiving standard therapy. Clinical rheumatology 2014, 33(10):1451-8.

32. Li B, Yue Y, Dong C, Shi Y, Xiong S: Blockade ofmacrophage autophagy ameliorates activated lymphocytes-derived DNA inducedmurine lupus possibly via inhibition of proinflammatory cytokines production. Clinical and experimental rheumatology 2014,32(5):705-14.

33. Liu L, Yue Y, Xiong S: NK-derived IFN-gamma/IL-4 triggersthe sexually disparate polarization of macrophages in CVB3-induced myocarditis.Journal of molecular and cellular cardiology 2014, 76:15-25.

34 .Mao X, Wu Y, Diao H, Hao J, Tian G, Jia Z, Li Z, Xiong S,Wu Z, Wang P, Zhao L, Yin Z: Interleukin-6 promotes systemic lupuserythematosus progression with Treg suppression approach in a murinesystemic lupus erythematosus model. Clinical rheumatology 2014, 33:1585–1593.

35. Wan X, Liu L, Ding X, Zhou P, Yuan X, Zhou Z, Hu P, ZhouH, Li Q, Zhang S, Xiong S, Zhang Y: Mll2 Controls Cardiac LineageDifferentiation of Mouse Embryonic Stem Cells by Promoting H3K4me3 Depositionat Cardiac-Specific Genes. Stem cell reviews 2014,10(5):643-52.

36. Wu F, Fan X, Yue Y, Xiong S, Dong C: A vesicularstomatitis virus-based mucosal vaccine promotes dendritic cell maturation andelicits preferable immune response against coxsackievirus B3 induced viralmyocarditis. Vaccine 2014, 32(31):3917-3926.

37. Xiao P, Dong C, Yue Y, Xiong S: Dynamic e­xpression ofmicroRNAs in M2b polarized macrophages associated with systemic lupuserythematosus. Gene 2014, 547(2):300-309.

38. Ye T, Yue Y, Fan X, Dong C, Xu W, Xiong S: Mcell-targeting strategy facilitates mucosal immune response and enhancesprotection against CVB3-induced viral myocarditis elicited by chitosan-DNAvaccine. Vaccine 2014, 32(35):4457-4465.

39. Zhang R, Wang K, Lv W, Yu W, Xie S, Xu K, Schwarz W,Xiong S, Sun B: The orF4a protein of human coronavirus 229E functions as aviroporin that regulates viral production. Biochimica et biophysica acta 2014, 1838(4):1088-1095.

40. Ding L, Gu H, Gao X, Xiong S, Zheng B: Aurora Kinase ARegulates M1 Macrophage Polarization and Plays a Role in ExperimentalAutoimmune Encephalomyelitis. Inflammation 2014.

41. Ma L, Shen CJ, Cohen EA, Xiong SD, Wang JH: miRNA-1236inhibits HIV-1 infection of monocytes by repressing translation of cellularfactor VprBP. PloS one 2014, 9(6):e99535.

42. Wang Y, Gao B, Xiong S: Involvement of NLRP3 inflammasomein CVB3-induced viral myocarditis. American journal of physiology Heart and circulatory physiology 2014, 307(10):H1438-1447.

43. Ren XX, Ma L, Liu QW, Li C, Huang Z, Wu L, Xiong SD, WangJH, Wang HB: The molecule of DC-SIGN captures enterovirus 71 and confersdendritic cell-mediated viral trans-infection. Virology journal 2014, 11:47.

44. Gao B, Wang Y, Xu W, Li S, Li Q, Xiong S: Inhibition of histonedeacetylase activity suppresses IFN-gamma induction of tripartite motif 22 viaCHIP-mediated proteasomal degradation of IRF-1. J Immunol 2013,191(1):464-471.

45. Wen Z, Xu L, Chen X, Xu W, Yin Z, GaoX, Xiong S: Autoantibody induction by DNA-containing immune complexes requires HMGB1 with theTLR2/microRNA-155 pathway. J Immunol 2013, 190(11):5411-5422.

46. Zhang W, Zhou Q, Xu W, Cai Y, Yin Z, GaoX, Xiong S: DNA-dependent activator of interferon-regulatory factors (DAI) promotes lupus nephritis by activating the calcium pathway. J Biol Chem 2013, 288(19):13534-13550.

47. Gao B, Xu W, Zhong L, Zhang Q, Su Y, Xiong S: p300, but not PCAF,collaborates with IRF-1 in stimulating TRIM22 e-xpression independently of its histone acetyltransferase activity. Eur J Immunol 2013, 43(8):2174-2184.

48. Cao Y, Xu W, Xiong S: Adoptive transfer of regulatory T cells protects against Coxsackie virus B3-induced cardiac fibrosis. PLoS One 2013, 8(9):e74955.

49. Cai Y, Zhang W, Xiong S: Mannose-binding lectin blunts macrophage polarization and ameliorates lupus nephritis. PLoS One 2013,8(4):e62465.

50. Chen X, Wen Z, Xu W, Xiong S: Granulin exacerbates lupusnephritis via enhancing macrophage M2b polarization. PLoS One 2013,8(6):e65542.

51. Wen Z, Xu L, Xu W, Yin Z, Gao X, Xiong S: Interleukin-17 e-xpression positively correlates with disease severity of lupus nephritis by increasing anti-double-stranded DNA antibody production in a lupus model induced by activated lymphocyte derived DNA. PLoS One 2013, 8(3):e58161.

52. Zhang W, Cai Y, Xu W, Yin Z, Gao X, Xiong S: AIM2 facilitates the apoptotic DNA-induced systemic lupus erythematosus via arbitrating macrophage functional maturation. J Clin Immunol 2013, 33(5):925-937.

53. Gao B, Xu W, Wang Y, Zhong L, Xiong S: Induction of TRIM22 byIFN-gamma Involves JAK and PC-PLC/PKC, but Not MAPKs and pI3K/Akt/mTORPathways. J Interferon Cytokine Res 2013, 33(10):578-587.

54. Kong H, Dong C, Xiong S: A novel vaccine p846 encodingRv3615c, Mtb10.4, and Rv2660c elicits robust immune response and alleviateslung injury induced by Mycobacterium infection. Hum Vaccin Immunother 2013,10(2).

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