黄文林
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。
个性化签名
- 姓名:黄文林
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学术头衔:
博士生导师
- 职称:-
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学科领域:
医学微生物学
- 研究兴趣: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。
黄文林,博士,中山大学肿瘤防治中心教授、博士生导师。1998-2001年,任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年回到中山大学,任中山大学肿瘤防治中心教授、博士生导师,《癌症》副主编。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(PolⅡ、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。后期进行抗艾滋病核酸药物的研究。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。
主编国家卫生部研究生教材《分子病毒学》及《信号转导》一书。
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10
黄文林, Ran-Yi Liu a, Li-Zhi Wu a, Bi-Jun Huanga, Jia-Ling Huanga, Yan-Ling Zhang a, Miao-La Ke a, Jun-Mei Wang b, Wei-Ping Tan c, Ru-Hua Zhang a, Han-Kui Chena, Yi-Xin Zenga, Wenlin Huanga, *
Virus Research xxx(2005)xxx-xxx,-0001,():
-1年11月30日
The causative agent of severe acute respiratory syndrome (SARS) has been identified as SARS-associated coronavirus (SARS-CoV), but the prophylactic treatment of SARS-CoV is still under investigation. We constructed a recombinant adenovirus containing a truncated N-terminal fragment of the SARS-CoV Spike (S) gene (from−45 to 1469, designated Ad-SN), which encoded a truncated Sprotein (490 amino-acid residues, a part of 672 amino-acid S1 subunit), and investigated whether this construct could induce effective immunity against SARS-CoV in Wistar rats. Rats were immunized either subcutaneously or intranasally with Ad-SN once a week for three consecutive weeks. Our results showed that all of the immunized animals generated humoral immunity against the SARS-CoV Spike protein, and the sera of immunized rats showed strong capable of protecting from SARS-CoV infection in vitro. Histopathological examination did not find evident side effects in the immunized animals. These results indicate that an adenoviral-based vaccine carrying an N-terminal fragment of the Spike gene is able to elicit strong SARS-CoV-specific humoral immune responses in rats, and may be useful for the development of a protective vaccine against SARS-CoV infection.
Vaccine, SARS-associated coronavirus, Adenoviral vector, Spike gene, Humoral immunity
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【期刊论文】In vivo transcription from the adenovirus E2 early promoter by RNA polymerase Ⅲ
黄文林, WENLIN HUANG, R. PRUZAN, AND S. J. FLINT*
Proc. Nati. Acad. Sci. USA Vol. 91, pp. 1265-1269, February 1994,-0001,():
-1年11月30日
We have previously reported that the subgroup C adenovirus E2 early (E2E) RNA polymerase 11 promoter can specify efficient in vitro transcription by RNA polymerase m. We now show that promoter proximal sequences of the E2E transcription unit are also transcribed by RNA polymerase Ill in nuclei isolated from adenovirusinfected cells. Small E2E RNA species that possessed the same properties as in vitro synthesized RNA polymerase m E2E transcripts were detected in cytoplasmic RNA populations from infected cells by using blotting, primer extension, and RNase protection assays. The 3' termini of these RNAs were mapped to thymidine-rich sequences typical of RNA polymerasemtermination sites. These results demonstrate that a single gene can be transcribed by both RNA polymerase II and RNA polymerase m in vivo.
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黄文林, LIANG Zhi-hui*, WU Pei-hong*, LI Li*, XUE Gang, ZENG Yi-xin and HUANG Wen-lin
Chinese Medical Journal 2004; 117 (12): 1809-1814,-0001,():
-1年11月30日
antiangiogenesis
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黄文林
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-1年11月30日
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【期刊论文】Endostatin gene therapy for liver cancer by a recombinant adenovirus delivery
黄文林, Li Li, Jia-Ling Huang, Qi-Cai Liu, Pei-Hong Wu, Ran-Yi Liu, Yi-Xin Zeng, Wen-Lin Huang
Microbes and Infection 7(2005)427-436,-0001,():
-1年11月30日
To investigate the expression of adenovirus-mediated human endostatin (Ad/hEndo) gene transfer and its effect on the growth of hepatocellular carcinoma (HCC) BEL-7402 xenografted tumors.
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黄文林, Jia-Ling Huang a, Jian Huang b, Zhao-Hui Duan c, JingWei d, Jun Min b, Xiao-Hong Luo c, Jian-Guo Li e, Wei-Ping Tan f, Li-ZhiWu a, Ran-Yi Liu a, Yan Li a, Jing Shao d, Bi-Jun Huang a, Yi-Xin Zeng a, Wenlin Huang a, *
Microbes and Infection 7(2005)427-436,-0001,():
-1年11月30日
The immune spectrum of severe acute respiratory syndrome (SARS) is poorly understood. To define the dynamics of the immune spectrum in SARS, serum levels of cytokines, chemokines, immunoglobulins, complement and specific antibodies against SARS-associated coronavirus (SARS-CoV) were assayed by enzyme-linked immunosorbent assay (ELISA), and phenotypes of peripheral lymphocytes were analyzed by flow cytometry in 95 SARS-infected patients. Results showed that interleukin (IL)-10 and transforming growth factor β (TGF-β) were continuously up-regulated during the entirety of SARS. Regulated on activation normally Tcell-expressed and secreted (RANTES) levels were decreased, while monocyte chemoattractant protein-1 (MCP-1) was elevated in acute patients. Immunoglobulins and complement were elevated during the first month of SARS. Both serum-positive rates and titers of specific IgM and IgG antibodies responding to SARS-CoV peaked at days 41-60 from the onset of SARS. CD4+ and CD8+Tlymphocytes decreased significantly in acute-phase. CD3+CD8+CD45RO+Tlymphocytes were decreased by 36.78% in the convalescent patients. Conclusion: SARS-CoV seemed to elicit effective humoral immunity but inhibited cellular immunity, especially CD8+memory Tlymphocytes over time. Prolonged overproduction of IL-10 and TGF-β may play an important role in the disease.
Severe acute respiratory syndrome, Immune monitoring, Immune system
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黄文林
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-1年11月30日
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黄文林, Ronald Pruzan, Pradeep K.Chatterjee+ and S.J. Flint*
Nucleic Acids Research, Vol. 20, No.21,-0001,():
-1年11月30日
The early E2 (E2E) promoter of adenovirus type 2 possesses a TATA-like element and binding sites for the factors E2F and ATF. This promoter is transcribed by RNA polymerase 11 in high salt nuclear extracts, but by RNA polymerase Ⅲ in standard nuclear extracts, as judged by sensitivity to low and high, respectively, concentrations of a-amanitin. Transcription by the two RNA polymerases initiated at the same site and depended, in both cases, on the TATA-like sequence and upstream elements. However, RNA polymerase Ill transcripts, unlike those synthesized by RNA polymerase 11, terminated at two runs of Ts downstream of the initiation site. Although they are not essential, sequences downstream of the initiation site increased the efficiency of E2E transcription by RNA polymerase Ⅲ. Such RNA polymerase Ⅲ dependent transcription required a subpopulation of the general transcription factor, TFIID: TFIID that binds weakly to phosphocellulose (0.3 M eluate) complemented a TFIIDdepleted extract to restore RNAp Ⅲ transcription, whereas TFIID tightly associated with phosphocellulose (1 M eluate) was unable to do so.
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黄文林
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-1年11月30日
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黄文林, Wenlin Huang† and S. J. Flint*
JOURNAL OF VIROLOGY, Apr. 2003, p. 4015-4024,-0001,():
-1年11月30日
In adenovirus type 5-infected cells, RNA polymerase Ⅲ transcription of a gene superimposed on the 5 end of the E2E RNA polymerase Ⅱ transcription unit produces two small (<100-nucleotide) RNAs that accumulate to low steady-state concentrations (W. Huang, R. Pruzan, and S. J. Flint, Proc. Natl. Acad. Sci. USA 91: 1265-1269, 1984). To gain a better understanding of the function of this RNA polymerase III transcription, we have examined the properties of the small E2E RNAs and E2E RNA polymerase III transcription in more detail. The accumulation of cytoplasmic E2E RNAs and the rates of E2E transcription by the two RNA polymerases during the infectious cycle were analyzed by using RNase T1 protection and run-on transcription assays, respectively. Although the RNA polymerase III transcripts were present at significantly lower concentrations than E2E mRNA throughout the period examined, E2E transcription by RNA polymerase Ⅲ was found to be at least as efficient as that by RNA polymerase Ⅱ. The short half-lifes of the small E2E RNAs estimated by using the actinomycin D chase method appear to account for their limited accumulation. The transcription of E2E sequences by RNA polymerase Ⅱ and Ⅲ in cells infected by recombinant adenoviruses carrying ectopic E2E-CAT (chloramphenicol transferase) reporter genes with mutations in E2E promoter sequences was also examined. The results of these experiments indicate that recognition of the E2E promoter by the RNA polymerase Ⅱ transcriptional machinery in infected cells limits transcription by RNA polymerase Ⅲ, and vice versa. Such transcriptional competition and the properties of E2E RNAs made by RNA polymerase Ⅲ suggest that the function of this viral RNA polymerase Ⅲ transcription unit is unusual.
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