专职PI
胡维国 研究员
研究员,博士生导师
E-mail: weiguohu@fudan.edu.cn
 

  1994年与1997年分别于第二军医大学获医学学士与医学硕士学位,2004年于中国科学院原上海生物化学研究所获理学博士学位,随后赴美耶鲁大学医学院肿瘤中心进行博士后研究,并于2005年转至哈佛大学医学院转化研究实验室,任Senior Research Associate,从事先天性免疫补体系统的基础与应用研究。2010年5月起任复旦大学生物医学研究院和复旦大学附属肿瘤医院/肿瘤研究所双聘PI,国家教育部“新世纪优秀人才”,上海市高校“东方学者”特聘教授及跟踪计划,上海市“浦江人才”。研究成果以第一/通讯作者发表在“Nature Medicine”, “Blood”, “Cancer Research” , “Journal of Immunology”, “JBC”, “FASEB J”,"Oncogene", "Stem Cell Reports" 等杂志,申报美国/国际专利7项 、国内专利2项。曾先后获得军队科技进步二等奖、美国心脏协会Junior Investigator Award、美国临床免疫学学会Travel Award等奖励。获科技部“973”项目和重大专项,基金委重大研究计划培育项目和面上项目等资助。


研究领域:

  研究补体系统在慢性炎症恶性转化、肿瘤治疗耐药、肿瘤侵袭转移、肿瘤免疫治疗中的作用及机制,并研发补体抑制剂用于疾病治疗。
  补体系统是先天性免疫的重要组成部分,也是连接先天性免疫与获得性免疫的桥梁。它的基本生理功能为清除细胞碎片,凋亡/死亡细胞和免疫复合物,以及入侵的病原体。另外,还可协调整个免疫和炎症反应,同时功能进一步进化并参与神经突触成熟,血管生成,造血干细胞的迁移动员,组织再生和脂质代谢,广泛参与不同的免疫反应性疾病,炎症,肿瘤,神经退行性疾病等的发生发展。补体系统激活后的酶切产物C3b/iC3b可“标记”待清除的细胞,表达于固有免疫细胞膜表面的相应受体与之结合后可清除这些异常细胞成分;酶切产物C5a是强烈的促炎症因子,也具有很强的趋化因子功能,可在补体激活局部诱发强烈的免疫反应;而补体激活终末阶段形成的膜攻击复合物(Membrane Attack Complex, MAC)则可直接裂解待清除的病原体,也可诱发广泛而复杂的下游信号途径。为了防止补体激活后对正常细胞的误伤效应,宿主细胞膜表面表达有补体膜调控蛋白包括CD59,在补体激活的不同阶段抑制补体的激活而保护宿主细胞。正常生理情况下,补体系统在激活与调控之间维持着精妙的平衡,一旦这种平衡被打破,补体系统激活不足则可能导致感染慢性持续化,而补体过度激活则导致全身或局部的持续性慢性炎症,广泛参与人类疾病包括肿瘤的发生与发展,而补体系统在肿瘤中的作用及机制研究国际上尚处于起步阶段。本实验室基于9种补体成分基因敲除小鼠、相应的补体系统检测平台及补体激动剂和抑制剂,探讨补体系统在慢性炎症恶性转化、肿瘤治疗耐药、肿瘤侵袭转移、肿瘤免疫治疗中的作用及机制,同时研发补体调控剂主要是补体抑制剂用于自身免疫性疾病的治疗。


图:补体系统的激活与调控。实验室9种基因敲除小鼠以及研究方向。


研究团队:



代表性论著:

  1. Chen J, Ding P, Li L, Gu H, Zhang X, Zhang L, Wang N, Gan L, Wang Q, Zhang W, Hu W*. CD59 regulation by SOX2 is required for epithelial cancer stem cells to evade complement surveillance. Stem Cell Reports 2017 Jan 10; 8(1):140-151.
  2. Zhang X, Zhang L, Du Y, Zheng H, Zhang P, Sun Y, Wang Y, Chen J, Ding P, Wang N, Yang C, Huang T, Yao X, Qiao Q, Gu H, Cai G, Cai S, Zhou X, Hu W*. A novel FOXM1 isoform, FOXM1D, promotes epithelial-mesenchymal transition and metastasis through ROCKs activation in colorectal cancer. Oncogene, 2016 Jul 11. doi: 10.1038/onc.2016.249. [Epub ahead of print]
  3. Ding P, Li L, Huang T, Yang C, Xu E, Wang N, Zhang L, Gu H, Yao X, Zhou X, Hu W*. Complement component 6 deficiency increases susceptibility to dextran sulfate sodium-induced murine colitis. Immunobiology, 2016 Nov; 221(11):1293-303.
  4. Yang C, Ding P, Wang Q, Zhang L, Zhang X, Zhao J, Xu E, Wang N, Chen J, Yang G, Hu W*, Zhou X*. Inhibition of Complement Retards Ankylosing Spondylitis Progression. Scientific Reports, 2016 Oct 4; 6:34643.
  5. Chen J, Du Y, Ding P, Zhang X, Zhang L, Wang N, Hu W*. Mouse Cd59b but not Cd59a is upregulated to protect cells from complement attack in response to inflammatory stimulation. Genes and Immunity, 2015; 16(7):437-45.
  6. Qiao Q, Teng X, Wang N, Lu R, Guo L, Zhang X, Du Y, Wang W, Chen S, Wu Q, He G, Wang Y, Hu W*. A novel CRIg-targeted complement inhibitor protects cells from complement damage. FASEB J, 2014; 28(11):4986-99.
  7. Du Y, Teng X, Wang N, Zhang X, Chen J, Ding P, Qiao Q, Wang Q, Zhang L, Yang C, Yang Z, Chu Y, Du X, Zhou X*, Hu W*. NF-κB and enhancer-binding CREB protein scaffolded by CREB-binding protein (CBP)/p300 proteins regulate CD59 protein expression to protect cells from complement attack. J Biol Chem, 2014; 289(5):2711-24.
  8. Hu W*, Ge X, You T, Xu T, Zhang J, Wu G, Peng Z, Chorev M, Aktas BH, Halperin JA, Brown JR, and Qin X*. Human CD59 inhibitor sensitizes rituximab-resistant lymphoma cells to complement-mediated cytolysis. Cancer Research, 2011; 71(6):2298-307.
  9. Zhang J, Hu W, Xing W, You T, Qin X, Peng Z*. The protective role of CD59 and pathogenic role of complement in hepatic ischemia and reperfusion injury. American Journal of Pathology, 2011; 179(6):2876-84.
  10. Ge X, Wu L, Hu W, Fernandes S, Wang C, Li X, Brown JR, Qin X*. rILYd4, a Human CD59 Inhibitor Enhances Complement Dependent Cytotoxicity of Ofatumumab against Rituximab-resistant B-cell Lymphoma Cells and Chronic Lymphocytic Leukemia. Clinical Cancer Research, 2011; 17(21):6702-11.
  11. Hu W#, Jin R#, Zhang J, You T, Bronson RT, Peng Z, Ge X, Loscalzo J, and Qin X*. The Mechanisms of Fatal Pulmonary Arterial Hypertension in a Unique Rapid Hemolysis Model. Blood, 2010; 116(9):1613-22.
  12. Hu W#, Yu Q#, Hu N, Byrd D, Shikuma C, Shiramizu B, Halperin JA, Qin X*. A high affinity inhibitor of human CD59 enhances complement-mediated virolysis of HIV-1: Implications for treatment of HIV-1/AIDS. Journal of Immunology, 2010; 184(1):359-368. (reported in NewScientist & Newsrx.com.)
  13. Wu G, Chen T, Shahsafaei A, Hu W, Bronson RR, Shi GP, Halperin JA, and Qin X*. Complement regulator CD59 protects against angiotensin II-induced abdominal aortic aneurysms in mice. Circulation, 2010; 121(11): 1338-1346.
  14. Qin X #, Hu W#, Song W, Grubissich L, Song Y, Wu G, Hu X, Ferris S, Dobarro M, Bauer S, Feelisch M, Leopold JA, Loscalzo J, Halperin JA*. Balancing role of nitric oxide in complement-mediated platelet activation of mCd59a and mCd59b double knockout mice. American Journal of Hematology, 2009; 84(4):221-7.
  15. Wu G, Hu W, Shahsafaei A, Song W, Dobarro M, Sukhova GK, Bronson RR, Shi GP, Rother RP, Halperin JA, and Qin X*. Complement regulator CD59 protects against atherosclerosis by restricting the formation of the complement membrane attack complex. Circulation Research, 2009; 104(4):550-8.
  16. Qin X, Hu W, Song W, Grubissich L, Hu X, Wu G, Ferris S, Dobarro M, Halperin JA*. Generation and phenotyping of mCd59a and mCd59b double-knockout mice. American Journal of Hematology, 2009; 84(2):65-70.
  17. Hu W, Ferris S, Tweten RK, Wu G, Gao B, Bronson RT, Halperin JA and Qin X*. Conditional, rapid and targeted ablation of cells expressing human CD59 in transgenic mice by intermedilysin. Nature Medicine, 2008 Jan; 14(1):98-103.
  18. Zhou X#, Hu W#, Qin X*. The Role of Complement in the Mechanism of Action of Rituximab for B-Cell Lymphoma: Implications for Therapy. Oncologist, 2008 Sep; 13(9):954-66.
  19. Qin X, Ferris S, Hu W, Guo F, Ziegeler G and Halperin JA*. Analysis of the promoters and 5'-UTR of mouse Cd59 genes, and of their functional activity in erythrocytes. Genes & Immunity, 2006; 7(4):287-97.
  20. Hu W, Li F, Yang X, Li Z, Xia H, Li G, Wang Y, Zhang Z*. A flexible peptide linker enhances the immunoreactivity of two copies HBsAg preS1 (21-47) fusion protein. Journal of Biotechnology, 2004 Jan 8; 107(1):83-90.
 
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