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                  專職PI
                  胡維國 研究員
                  研究員,博士生導師
                  E-mail: weiguohu@fudan.edu.cn
                   

                    1994年與1997年分別于第二軍醫大學獲醫學學士與醫學碩士學位,2004年于中國科學院原上海生物化學研究所獲理學博士學位,隨后赴美耶魯大學醫學院腫瘤中心進行博士后研究,并于2005年轉至哈佛大學醫學院轉化研究實驗室,任Senior Research Associate,從事先天性免疫補體系統的基礎與應用研究。2010年5月起任復旦大學生物醫學研究院和復旦大學附屬腫瘤醫院/腫瘤研究所雙聘PI,國家教育部“新世紀優秀人才”,上海市高校“東方學者”特聘教授及跟蹤計劃,上海市“浦江人才”。研究成果以第一/通訊作者發表在“Nature Medicine”, “Blood”, Cancer Research”, “Journal of Immunology”, “JBC”, “FASEB J”, “Oncogene”, “Stem Cell Reports”等雜志,申報美國/國際專利7項 、國內專利2項。曾先后獲得軍隊科技進步二等獎、美國心臟協會Junior Investigator Award、美國臨床免疫學學會Travel Award等獎勵。獲科技部“973”項目和重大專項,基金委重大研究計劃集成項目、培育項目和面上項目等資助。


                  研究領域:

                    研究補體系統在慢性炎癥惡性轉化、腫瘤治療耐藥、腫瘤侵襲轉移、腫瘤免疫治療中的作用及機制,并研發補體抑制劑用于疾病治療。
                    補體系統是先天性免疫的重要組成部分,也是連接先天性免疫與獲得性免疫的橋梁。它的基本生理功能為清除細胞碎片,凋亡/死亡細胞和免疫復合物,以及入侵的病原體。另外,還可協調整個免疫和炎癥反應,同時功能進一步進化并參與神經突觸成熟,血管生成,造血干細胞的遷移動員,組織再生和脂質代謝,廣泛參與不同的免疫反應性疾病,炎癥,腫瘤,神經退行性疾病等的發生發展。補體系統激活后的酶切產物C3b/iC3b可標記待清除的細胞,表達于固有免疫細胞膜表面的相應受體與之結合后可清除這些異常細胞成分;酶切產物C5a是強烈的促炎癥因子,也具有很強的趨化因子功能,可在補體激活局部誘發強烈的免疫反應;而補體激活終末階段形成的膜攻擊復合物(Membrane Attack Complex, MAC)則可直接裂解待清除的病原體,也可誘發廣泛而復雜的下游信號途徑。為了防止補體激活后對正常細胞的誤傷效應,宿主細胞膜表面表達有補體膜調控蛋白包括CD59,在補體激活的不同階段抑制補體的激活而保護宿主細胞。正常生理情況下,補體系統在激活與調控之間維持著精妙的平衡,一旦這種平衡被打破,補體系統激活不足則可能導致感染慢性持續化,而補體過度激活則導致全身或局部的持續性慢性炎癥,廣泛參與人類疾病包括腫瘤的發生與發展,而補體系統在腫瘤中的作用及機制研究國際上尚處于起步階段。本實驗室基于9種補體成分基因敲除小鼠、相應的補體系統檢測平臺及補體激動劑和抑制劑,探討補體系統在慢性炎癥惡性轉化、腫瘤治療耐藥、腫瘤侵襲轉移、腫瘤免疫治療中的作用及機制,同時研發補體調控劑主要是補體抑制劑用于自身免疫性疾病的治療。


                  圖:補體系統的激活與調控。實驗室9種基因敲除小鼠以及研究方向。


                  研究團隊:




                  代表性論著:

                  1. Ding P, Li L, Li L, Lv X, Zhou D, Wang Q, Chen J, Yang C, Xu E, Dai W, Zhang X, Wang N, Wang Q, Zhang W, Zhang L, Zhou Y, Gu H, Lei Q, Zhou X, Hu W*. C5aR1 is a master regulator in Colorectal Tumorigenesis via Immune modulation. Theranostics, 2020 Jul 9; 10(19):8619-8632.
                  2. Wang Q#, Zhang P#, Zhang W, Zhang X, Chen J, Ding P, Li L, Lv X, Li L, Hu W*. PI3K Activation Is Enhanced by FOXM1D Binding to p110 and p85 Subunits. Signal Transduct Target Ther, 2020 Jun 30; 5(1):105.
                  3. Chen J, Ge X, Zhang W, Ding P, Du Y, Wang Q, Li L, Fang L, Sun Y, Zhang P, Zhou Y, Zhang L, Lv X, Li L, Zhang X, Zhang Q, Xue K, Gu H, Lei Q, Wong J, Hu W*. PI3K/AKT Inhibition Reverses R-CHOP Resistance by Destabilizing SOX2 in Diffuse Large B Cell Lymphoma. Theranostics, 2020 Feb 10; 10(7):3151-3163.
                  4. Zhang L, Wang Q, Zhou Y, Ouyang Q, Dai W, Chen J, Ding P, Li L, Zhang X, Zhang W, Lv X, Li L, Zhang P, Cai G, Hu W*. Overexpression of MTA1 inhibits the metastatic ability of ZR-75-30 cells in vitro by promoting MTA2 degradation. Cell Commun Signal, 2019 Jan 14; 17(1):4. doi: 10.1186/s12964-019-0318-6.
                  5. Ge X, Chen J, Li L, Ding P, Wang Q, Zhang W, Li L, Lv X, Zhou D, Jiang Z, Zeng H, Xu Y, Hou Y*, Hu W*. Midostaurin potentiates rituximab antitumor activity in Burkitt's lymphoma by inducing apoptosis. Cell Death Dis., 2018 Dec 18; 10(1):8.
                  6. Hu C, Li L, Ding P, Li L, Ge X, Zheng L, Wang X, Wang J, Zhang W, Wang N, Gu H, Zhong F, Xu M, Rong R, Zhu T*, Hu W*. Complement Inhibitor CRIg/FH Ameliorates Renal Ischemia Reperfusion Injury via Activation of PI3K/AKT Signaling. J Immunol., 2018 Dec 15; 201(12):3717-3730.
                  7. Zhou Y, Wang Q, Chu L, Dai W, Zhang X, Chen J, Zhang L, Ding P, Zhang X, Gu H, Zhang P, Li L, Zhang W, Li L, Lv X, Zhou D, Cai G, Chen L, Zhao K, Hu W*. FOXM1c promotes oesophageal cancer metastasis by transcriptionally regulating IRF1 expression. Cell Prolif., 2018 Nov 28:e12553.
                  8. Liu Y, Guo JZ, Liu Y, Wang K, Ding W, Wang H, Liu X, Zhou S, Lu XC, Yang HB, Xu C, Gao W, Zhou L, Wang YP, Hu W, Wei Y, Huang C, Lei QY. Nuclear lactate dehydrogenase A senses ROS to produce α-hydroxybutyrate for HPV-induced cervical tumor growth. Nat Commun., 2018 Oct 24; 9(1):4429.
                  9. Zhou Y, Chu L, Wang Q, Dai W, Zhang X, Chen J, Li L, Ding P, Zhang L, Gu H, Li L, Lv X, Zhang W, Zhou D, Zhang P, Cai G, Zhao K*, Hu W*. CD59 is a potential biomarker of esophageal squamous cell carcinoma radioresistance by affecting DNA repair. Cell Death Dis., 2018 Aug 30; 9(9):887.
                  10. Wang S, Peng Z, Wang S, Yang L, Chen Y, Kong X, Song S, Pei P, Tian C, Yan H, Ding P, Hu W, Liu CH, Zhang X, He F, Zhang L. KRAB-type zinc-finger proteins PITA and PISA specifically regulate p53-dependent glycolysis and mitochondrial respiration. Cell Res., 2018 Feb 21. doi: 10.1038/s41422-018-0008-8.
                  11. 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.
                  12. 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, 2017 Feb 9;36(6):807-819. 
                  13. 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.
                  14. 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.
                  15. 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.
                  16. 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.
                  17. 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.
                  18. 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.
                  19. 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.
                  20. 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.
                  21. 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.
                  22. 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.)
                  23. 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.
                  24. 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.
                  25. 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.
                  26. 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.
                  27. 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.
                  28. 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.
                  29. 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.
                  30. 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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