黄文林研究员
黄文林
博士,研究员,博士生导师
主要履历及经历
1974-1977年 三峡大学医学院
1977-1988年 武汉病毒中心助理研究员
1988-1996年 普林斯顿大学分子生物学博士，助理研究员
1996-1997年 美国Allegheny大学副教授
1998-2001年 美国普林斯顿大学分子生物学系项目负责人，纽约高等病毒研究所资深科学家，中山医科大学肿瘤防治中心客座教授
2001-2005年 中山大学肿瘤防治中心教授、博士生导师，《癌症》副主编
2006-至今 中国科学院微生物研究所研究员、博士生导师， 香港中文大学荣誉教授
主要研究领域
主要从事个基因治疗及靶点药物的研究。包括，受体酪氨酸激酶抑制剂及其抗瘤作用研究；重组人内皮抑素腺病毒注射液及其抗瘤作用研究；重组人IFN- g腺病毒注射液及其抗瘤作用研究；携带人IFN-g的小环DNA载体抗瘤作用。同时对禽流感致病机制和人乳头瘤状病毒疫苗的研制进行研究以及腺病毒感染细胞后期选择性抑制mRNA转送的机制的研究。
承担课题
承担了国家“十五”攻关、“863”计划、国家“973”计划及广东省关键领域重点突破等项目。包括禽流感病毒感染上皮细胞分子机制的研究；基因治疗的应用基础研究-新型病毒载体系统的研究；SARS病毒S蛋白功能研究；新型基因治疗药物——重组人内皮抑素腺病毒的研制；基因治疗的关键技术及产品开发；重组人内皮抑素腺病毒抗癌制剂的中试放大；疫苗研制——基因疫苗组；SARS相关冠状病毒疫苗的研制；以基因治疗为核心的多种方式治疗肿瘤的研究等。
研究内容
从事研究项目“腺病毒感染细胞后期选择性抑制mRNA转送的机制”的研究，对腺病毒感染细胞后mRNA剪接、转送的动态及特异性DNA序列参与调控做了较系统的研究，首次证明腺病毒感染真核细胞后可主动调节真核细胞的功能基因，并且腺病毒早期启动子E2E能有效地同时利用两种RNA聚合酶（Pol Ⅱ、Ⅲ）进行竞争性高效转录。实验同时证实腺病毒晚期基因启动子三联先导序列（tpl）能有效地从细胞核将腺病毒晚期转录mRNA转运到胞浆优先表达，相关研究成果先后于1998年和2003年发表在《PNAS》和《Journal of Virology》。同时，进行了腺病毒载体携带NGF、NT3、HbsAg亚单位、Endostatin、Angiostatin、IFN-α，反转录病毒载体的构建，小分子化合物酪氨酸激酶受体抑制剂抗癌药物等研发。其中，重组人内皮抑素腺病毒抗癌注射液已经获得国家SFDA临床I期试验批文，正在向产业化方向发展。主要研究方向是抗血管生成基因治疗，应用生物载体如病毒、小环DNA等对治疗性基因如人内皮抑素、干扰素基因等携带到真核细胞，进行有效表达，产生治疗性产物。研究重点在载体的免疫特性，治疗基因的代谢、药效的分子机制以及大分子治疗物质与体内靶向性受体的相互作用的研究。研究对急性传染性非典型肺炎（SARS）感染人体后，T细胞亚群的动态。首先发现了SARS感染后可使人体T记忆细胞显著降低的生物学行为及免疫病理学指针，应用腺病毒 5型SARS-S基因的预防性疫苗的构建及小鼠体液性免疫研究，为SARS疫苗的研制提供了新思路。相关的研究成果发表在《International Journal of Cancer》、《Clinical Cancer Research》等期刊，主编国家卫生部研究生教材《分子病毒学》及《信号转导》，参编《肿瘤生物治疗》、《基因转录的调控》。
专利及推广应用
专利情况：
1 Assay method for determining Product’s R’s effect on adenovirus infection of HeLa cells, US patent:6440658
2 黄文林。一种人血管内皮细胞生长抑制因子的重组病毒。中国发明专利（专利号：ZL01 1 27894.3）
3 黄文林，等。一种喹淋衍生物的制备方法及用作制备治疗肿瘤疾病药物的应用。国际发明专利（申请号：PCT/CN2005/000660）
4 黄文林，等。一种酪氨酸激酶抑制剂、其制备方法及作为抗肿瘤药物的应用。国际发明专利（申请号：PCT/CN2005/000661）
5 黄文林，等。一种作为抗肿瘤药物的喹淋衍生物及其制备方法。国际发明专利（申请号：PCT/CN2005/000663）
6 黄文林，等。一种作为抗肿瘤药物应用的酪氨酸激酶抑制剂及其制备方法。国际发明专利（申请号：PCT/CN2005/000662）
7 黄文林，等。腺病毒载体SARS疫苗及其制备方法，以及相关冠状病毒S基因在制备疫苗中的应用。国际发明专利（PCT/CN2004/000505）、中国发明专利（申请号：03126634.7）
8 黄文林，等。重组人γ-干扰素腺病毒（Ad-rhIFNγ）以及该产物的制备方法和在制备抗病毒药物中的应用。国际发明专利（PCT/CN2004/00427）、中国发明专利（申请号：03126707.6）
9 黄文林，等。一种酪氨酸激酶抑制剂及其制备方法和用途。中国发明专利（申请号：03114359.8）
10 黄文林，等。Assay method for determining Product R’s effect on adenovirus infection of hela cells。美国专利（US patent: 6440658）
11曾益新、黄文林，等。SARS核酸疫苗及其制备方法，以及相关冠状病毒S基因在制备疫苗中的应用。中国发明专利（申请号：03126635.5）
推广应用：
重组人内皮抑素腺病毒注射液与广州达博生物制品有限公司合作已开始临床验证，现已完成I期临床试验。
主要论文
1. Wu J, Xiao X, Xue G, Zhu Y, Zhao P, Zhu X, Zheng L, Huang W. Minicircle-IFNγ Induces Anti-proliferative and Anti-tumoral Effects in Human Nasopharyngeal Carcinoma. Clinical Cancer Research. 2006，12(15):4702-13
2. Xue G, Liu RY, Li Y, Cheng Y, Xiao X, Wu JX, Tian FZ, Huang W. Adenovirus Carrying 6Ckine/IFNγ Fusion Gene-modified Dendritic Cells Act as an Adjuvant to Induce Specific Antitumor Immunity. Submitted to Molecular Therapy
3. Hongli Li, … Wenlin Huang, Phase 1 Study of Pharmacokinetic and Pharmacodynamics on Intratumoral Injection of an Adenovirus Encoding Human Endosattin in Patients with Advanced Solid Tumor, Submitted to Journal of Clinical Investgation
4. Li L, Liu RY, Huang JL, Liu QC, Li Y, Wu PH, Zeng YX, Huang W. Adenovirus-mediated intra-tumoral delivery of the endostatin gene inhibits tumor growth in nasopharyngeal carcinoma. Int J Cancer, 118(8):2064-71, 2006
5. Huang BJ, Liu RY, Huang JL, Fu LW, Zhu YH, Huang W. Long-term Toxicity Studies in Canine of E10A an Adenoviral Vector Mediated Human Endostatin Gene. Submitted to Hum Gene Ther.
6. LB Song, WT Liao……W Huang, The Clinical Significance of Twist Expression in Nasopharyngeal Carcinoma, Cancer Letter, 2006
7. XF Liu, YF Xia…..W Huang, The Effect of p21 Antisense Oligodeoxynucleotides on the Radiosensitivity of Nasopharyngeal Carcinoma Cells with Normal p53 Function, Cell Biol. Intl, 2006, 30(3):287-7
8. JC Xia, DS Weng….W Huang, Loss of Heterozygosity Analysis of a Candidate Gastric Carcinoma Tumor Supressor Locus at 7q31, Cancer Genet Cyto Genet, 2006, 166(2):166-72
9. LB Song, MS Zeng,....W Huang, Bmi-1 is a Novel Molecular Marker of Nasopharyngeal Carcinoma Progression and Immortalizes Primary Human Nasopharygeal Epithelial Cells.Cancer Research, 2006, 66(12):6225-32
10. J-M Zhou….W-L Huang, Senescence and Telomere Shortening Induced by Novel Potent G-quadruplex Interactive Agents, Quindoline Derivatives, in Human Cancer Cell Lines, Oncogens, 2006, 25, 503-511
11. XiaoQing Li,….W. Huang, In vitro Effect of Adenovirus-mediated Human Gamma Interferon Gene Transfer into Human Mesenchymal Stem Cells for Chronic Myelogenously Leukemia, Hematological Oncology, 2006
12. Xiao Lin, Tan W., Huang W., The Biological Function of Tbet on the Microphage(Raw246.7) of Mice. Chinese Journal of Cancer.2006
13. Xue Gong…Huang WL, Construction of Recombinant Adenovirus Carrying Human IFN-γ Gene by in Vitro Ligation and its Expression, Chinese Journal of Cancer, 25(6):771-774, 2006
14. Xiao,Lin...Huang, W. GATA-3 transfusion in T Cell, Foreign Medical Sciences Blood Transfusion and Hematology,2005, 28:314-317
15. Liu, Ranyi…Huang, W. Construction of Adenovirus Harboring N-fragment of SARS-CoV, Journal of Sun Yat-sen University (Medical Sciences), 2005, 26:32-34
16. Liu, Ran-yi…Huang, W. Adenoviral Expression of a Truncated S1 Subunit of SARS-CoV Spike Protein Results in Specific Humoral Immune Responses Against SARS-CoV in Rats, Virus Research, 2005:24-31
17. Tan,Wei-ping…Huang,W. Construction of Murine T-bet cDNA Recombinant Adenovirus Vector and its Identification. Journal of Sun Yat-sen University(Medical Sciences), 2004,25:546-553
18. He, Gou-An….Huang, W. Dynamic Distribution and Expression in vivo of Human Endostatin Gene Deliveried by Adenoviral Vector, Life Science, 77:1331-1340,2005
19. Zhang, Yanlin…. Huang, Wenlin, etc. Evaluation of The Titer of Adenovirus with Immunological Method. Chi. J. Pathophysiology, 2005,21(4):830-832
20. Huang, Jialin….Huang, W. Th2 Predominance and CD8+ Memory T Cell Depletion in Patients with Severe Acute Respiratory Syndrome, Microbe and Infections, (7)427-436,2005
21. Li, Xiaoqing, Huang, Wenlin. In vitro Anti-leukeemic Effects of Bone Marrow Stromal Cells Modified with Ad/hIFN-r. Journal of Guangdong College of Pharmacy, 21:307-311, 2005
22. Huang,Jialing, Huang, Wenlin. Construction of Hepatocellular Carcinoma-Specific Eukarotypic Expression Vector Carrying Double Suicide Genes, Journal of Sun Yat-sen University (Medical Sciences),26(2):142-145, 2005
23. Wu, Jiangxue and Huang, Wenlin. Research Advancement of Endogenous Angiogenesis Inhibitors, Chinese Journal of Cancer, 24(3):376-384, 2005
24. Huang, W., S.J. Flint, Unusual Properties of Adenovirus E2E Transcription by RNA Polymerase III, Journal of Virology, 77, 4015-4024, 2003
25. Huang, W.; Flint, S.J. The Tripartite Leader Sequence of Subgroup C Adenovirus Major Late mRNA Can Increase the Efficiency of mRNA Export. Journal of Virology, 72, 225-235, 1998
26. Yang, U.C.; Huang, W.; Flint, S. J. Messenger RNA Export Correlates with Activation of Transcription in Human Subgroup C Adenovirus-Infected Cells. J. of Virology, 70, 4071-4080, 1996
27. Huang , W.; Pruzan, R.; Flint, S.J. In Vivo Transcription from the Adenovirus E2E Promoter by RNA Polymerase III. Proc. Natl. Acad. Sci., USA 91, 1265-1269, 1994
28. Huang, W., etc. Inhibition of Adenovirus E1A Expression in HeLa Cells by Product R, a Peptide Nucleic Acid Immunomodulator. Journal of Infectious Diseases, 31-1, 328-231. 2001
29. Huang, W., etc. A Peptide Nucleic Acid Complex, Interferes with Expression of the E7 Oncoprotein of Human Papilloma Virus-18 in HeLa Cells. Journal of Infectious Diseases, 31-1, 220-227. 2000
30. An, H…Huang, W., etc. Construction of p53 in Adenovirus Vector. Bulletin of Fourth Military Medical University, 21(2):220-222, 2000
31. Huang, W., etc. Construction of Inducible Adenovirus Expression Vector, Journal of Medicine Chin. 12:73-80, 1998
32. Huang, W., Daiming Fang, Distribution of mRNA Expression of The Tyrosine Kinase C Receptor in Rat Spinal Cord?6?2 by in Situ Hybridization. Biochemistry, 10.30;(S:S):344, 1997
33. Liu, Y…. Huang, W. etc., Application of Recombinant adenovirus for in vivo Gene Delivery to Spinal Cord. Brain Res, 768(1-2): 19-29, 1997
34. Huang, W.; Flint, S.J. The Tripartite Leader Sequence of Subgroup C Adenovirus Major Late mRNA Can Increase the Efficiency of mRNA Export. Journal of Virology, 72, 225-235, 1998
35. Yang, U.C.; Huang, W.; Flint, S. J. Messenger RNA Export Correlates with Activation of Transcription in Human Subgroup C Adenovirus-Infected Cells. J. of Virology, 70, 4071-4080, 1996
36. Huang, W.; Pruzan, R.; Flint, S.J. In Vivo Transcription from the Adenovirus E2E Promoter by RNA Polymerase III. Proc. Natl. Acad. Sci., USA 91, 1265-1269, 1994
37. Pruzan, R; Huang, W.; Chatterjee, P.K.; Flint, S.J. RNA Polymerase II Transcription of the Adenovirus 2 E2E Promoter. DNA Virus Conference in Cold Spring Harbor Lab, Aug. 12-16, 1992
38. Li, X.; Huang, W.; Flint, S.J. The Downstream Regulatory Sequence of the Adenovirus Type 2 Major Late Promoter Is Functionally Reductant. Journal of Virology, 66, 5685-5690, 1992
39. Huang, W.; etc., A Study on Screening of Cancers by Using Extract of Human Placenta. Health Care Journal, 6, 147-148, 1990
40. Huang, W.; etc., Inhibition of Porcine Spleen Interferon to Human Hemorrhagic Virus on Tissue Culture. Journal of Biopharmacia, 3, 107-110, 1989
41. Huang, W.; etc., Serological Study on the RHDV. Virologica Sinica, 1 ,90-95, 1989
42. Huang, W.; etc., Antigenic Relationship Between Porcine Spleen Cell Interferon and Human Leukocyte Interferon. Virologica Sinica, 2, 193-198, 1989
43. Huang, W.; etc., Some Antigenic Relationship between Porcine Spleen IFN and HuIFN by McAb of HuIFN-alpha. Biochemistry and Biophysics Sinica 15, 231-233, 1988
44. Huang, W.; etc., Separation of the Porcine Spleen Interferon (PsIFN) on Fast Performance Liquid Chromatography (FPLC). Progress in Biochemistry and Biophysics, 15, 231-233, 1988
45. Huang, W.; etc., Research on Porcine Spleen Interferon. Second SCBA International Symposium at University of California, Berkeley, June 27, 1988
46. Huang, W.; etc., Approval on the Identification and Classification of Rabbit Hemorrhagic Disease Virus in Wuhan Virologica Sinica, 1, 7,1988
47. Huang, W.; etc., Study on the Heterogenic of Some Animal IFNs. Journal of Biochemical Pharmaceutic, 3, 43-49, 1987
48. Huang, W.; etc., Some Problems of Animal IFNs Heterogenic. Biochemistry of the Life, 7, 9-10,1987
49. Huang, W.; etc., Production and Antiviral Effects of a Porcine Leukocyte IFN. Acta Virologica Sinica, 5, 57-62,1987
50. Zhang, G., Huang, W. Serological Study on NPV Protein and Virion from the NPV of Cotton Bollom. Acta Microbiological Sinica, 25, 262-269,1985
51. Huang, W.; etc., Serological Detection of Some Animal Inoculated with Nuclear Polyhedron Virus (NPV) of Cotton Bollom. Acta Virological Sinica, 3, 159-163,1983
