复旦大学基础医学院研究生导师简介-童舒平教授

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　　姓名：童舒平 博士
　　职称：特聘教授
　　E-MAIL: shupingtong@fudan.edu.cn
　　WWW: http://www.------
　　研究方向
　　1.人乙肝病毒的基因型与突变株
　　2.鸭子乙肝病毒与人乙肝病毒受体
　　3.HBV亚病毒颗粒表达调控及其生物学意义
　　重要学术贡献
　　本人为全球研究乙肝病毒遗传变异的公认专家，为不表达e抗原的乙肝病毒 (HBV) 前C区突变株的最早发现者之一 (Tong et al., 1990，Virology)，为此获得法国肝脏协会颁发的”Young Investigator”奖。随后发现前C区突变在HBV的A基因型罕见 (Tong et al., 1993, J. Virol; Li et al., 1993, J. Virol)，从而首次证明用基因型分类乙肝病毒的生物学意义。博士后期间鉴定并深入细致地分析了鸭子乙肝病毒 (DHBV) 的结合受体 (primary receptor: duck carboxypeptidase D) 与二级受体 (P protein of duck glycine decarboxylase)。为此，在NTCP被独立证明为人乙肝病毒受体后，被邀请审稿并撰写社论 (Tong & Li, 2014, Gastroenterology)。我们对于HBV基因型的研究发现：A基因型产生多种分子形式的e抗原，而G基因型的36个核苷酸插入显著促进核心蛋白表达;野生型C基因型的DNA复制能力低于B基因型，但病毒颗粒分泌能力更强; D基因型S蛋白表达低于A基因型，但表面抗原分泌能力更强。我们还发现胞膜蛋白S区的单一氨基酸改变与免疫逃避突变可以抑制完整病毒颗粒分泌。我们的总体目标是通过对病毒遗传变异株的分子生物学特性的鉴定，来解释它们的临床表现与致病性。
　　荣誉与获奖
　　2013 国际乙型肝炎分子生物学年会召集人之一
　　2014 第四批上海市千人计划专家
　　国内外学术团体任职
　　2009-2015 Jounal of Hepatology, 编委
　　2013-今 Journal of Virology, 编委
　　2014-今 Emerging Microbes & Infections, 编委
　　受邀审稿学术刊物
　　1999-今 Antimicrobial Agents & Chemotherapy, Antiviral Research, FEBS Letters, Clinical and Vaccine Immunology, Digestion, Gut, Hepatology, Gastroenterology, Gene Therapy, Journal of Clinical Microbiology, Journal of General Virology, Journal of Hepatology, Journal of Infectious Diseases, Journal of Medical Virology, Joural of Viral Hepatitis, Journal of Virology, Liver International, Nucleic Acids Research, PLOS One, PLOS Pathogens, Viral Immunology, Virology Journal, Viruses.

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　　发表论文
　　1.Zhang F., Tang X., Garcia T., Lok A., Wang Y., Jia H., Qin Y., Chen C., Wen Y., Li J., and Tong S*. 2017. Characterization of contrasting features between hepatitis B virus genotype A and genotype D in small envelope protein expression and surface antigen secretion. Virology 503: 52-61.
　　2.Jia, H., Qin, Y., Chen, C., Zhang, F., Li, C., Zong, L., Wang, Y., Zhang, J., Li, J., Wen, Y., Tong, S*. 2017. The envelope gene of hepatitis B virus is implicated in both differential virion secretion and genome replication capacities between genotype B and genotype C isolates. Viruses, 9: e62.
　　3.Zhou H., Gewaily D., Ahn S.H., Preskill C., Wang Y., Zong L., Zhang J., Han K.H., Wands J., Li J., Tong S*. 2017. Sequence analysis and functional characterization of full-length hepatitis B virus genomes from Korean cirrhotic patients with or without liver cancer. Virus Res. 235: 86-95.
　　4.Wang W., Sun L., Li T., Ma Y., Li J.., Liu Y., Li M., Wang L., Li C., Xie Y., Wen Y., Liang M., Chen L., and Tong S*. 2016. A human monoclonal antibody against small envelope protein of hepatitis B virus with potent neutralization effect. mAbs. 8:468-477.
　　5.Qin Y., Zhou X., Jia H., Chen C., Zhao W., Zhang J., Tong S*. 2016. Stronger enhancer II/core promoter activities of hepatitis B virus isolates of B2 subgenotype than those of C2 subgenotype. Scientific Reports 6, 30374.
　　6.Zong L., Qin Y., Jia H., Zhou H., Chen C., Wang Y.X., Zhang J., Li J., Tong S*. 2016. Two-way molecular ligation for efficient conversion of monomeric hepatitis B virus DNA constructs into replication competent tandem dimers. J. Virol. Meth. 233:46-50.
　　7.Chen C., Jia H., Zhang F., Qin Y., Zong L., Yuan Q., Wang Y., Xia N., Li J., Wen Y., Tong S*. 2016. Functional characterization of hepatitis B virus core promoter mutants revealed transcriptional interference among co-terminal viral mRNAs. J. Gen. Virol. 97:2668-2676.
　　8.Tong S.*, Revill P. 2016. Overview of hepatitis B viral replication and genetic variability. J. Heptol. 64(1 Suppl):S4-16.
　　9.Li J., Tong S*. 2015. From DCPD to NTCP: the long journey towards identifying a functional hepatitis B virus receptor. Clin. Mol. Hepatol. 21:193-199.
　　10.Tong S.*, Li J. 2014. Identification of NTCP as an HBV receptor: the beginning of the end or the end of the beginning? (editorial) Gastroenterology 146: 902-905.
　　11.Kwei K., Tang X., Lok A.S., Sureau C., Garcia T., Li J., Wands J., Tong S*. 2013. Impaired virion secretion by hepatitis B virus immune escape mutants and its rescue by wild-type envelope proteins or a second-site mutation. J. Virol. 87: 2352-2357.
　　12.Tong S.*, Li J., Wands J., Wen Y. 2013. Hepatitis B virus genetic variants: Biological properties and clinical implications. Emerging Microbes & Infections. 2, e10; doi: 10.1038/emi2013.10.
　　13.Tong S*. 2012. Hepatitis B virus, a sex hormone-responsive virus (editorial). Gastroenterology 142: 696-699.
　　14.Qin Y., Zhang J., Garcia T., Ito K., Gutelius D., Li J., Wands J., Tong S*. 2011. Improved method for rapid and efficient determination of genome replication and protein expression of clinical hepatitis B virus isolates. J. Clin. Microbiol. 49: 1226-1233.
　　15.Qin Y., Tang X., Garcia T., Hussain M., Zhang J., Lok A., Wands J., Li J., Tong S*. 2011. Hepatitis B virus genotype C isolates with wild-type core promoter sequence replicate less efficiently than genotype B isolates but possess higher virion secretion capacity. J. Virol. 85: 10167-10177.
　　16.Gutelius D., Li J., Wands J., Tong S*. 2011. Characterization of the pleiotropic effects of the genotype G-specific 36-nucleotide insertion in the context of other hepatitis B virus genotypes. J. Virol. 85: 13278-13289.
　　17.Ito K., Qin Y., Guarnieri M., Garcia T., Kwei K., Mizokami M., Zhang J., Li J., Wands J., Tong S*. 2010. Impairment of hepatitis B virus virion secretion by single amino acid substitutions in the small envelope protein and rescue by a novel glycosylation site. J. Virol. 84: 12850-12861.
　　18.Qin Y., Zhang J., Mao R., Guo H., Yin Y., Wu X., Weng X., Wands J., Tong S*. 2009. Prevalence of basal core promoter and precore mutations in Chinese chronic hepatitis B patients and correlation with serum HBeAg titers. J. Med. Virol. 81: 807-814.
　　19.Ito K., Kim K-H., Lok A., Tong S*. 2009. Characterization of genotype-specific carboxyl-terminal cleavage sites of hepatitis B virus e antigen precursor and identification of furin as the candidate enzyme. J. Virol. 83: 3507-3517.
　　20.Tsai A., Kawai S., Kwei K., Gewaily D., Hutter A., Tong D., Li J., Wands J., Tong S*. 2009. Chimeric constructs between two hepatitis B virus genomes confirm transcriptional impact of core promoter mutations and reveal multiple effects of core gene mutations. Virology 387: 364-372.
　　21.Garcia T., Li J., Sureau C., Ito K., Qin Y., Wands J., Tong S*. 2009. Drastic reduction in the production of subviral particles does not impair hepatitis B virus virion secretion. J. Virol. 83: 11152-11165.
　　22.Li K., Zoulim F., Pichoud C., Kwei K., Villet S., Wands J., Li J., Tong S*. 2007. Critical role of the 36-nucleotide insertion in hepatitis B virus genotype G on core protein expression, genome replication, and virion secretion. J. Virol. 81: 9202-9215.
　　23.Tong, S*. 2007. Impact of viral genotypes and naturally occurring mutations on biological properties of hepatitis B virus (review). Hepatol. Res. 37: s3-38.
　　24.Guarnieri M., Kim K., Bang G., Li J., Zhou Y., Tang X., Wands J., Tong S*. 2006. Point mutations upstream of hepatitis B virus core gene affect DNA replication at the step of core protein expression. J. Virol. 80: 587-595.
　　25.Bang G., Kim K., Guarnieri M., Zoulim F., Kawai S., Li J., Wands J., Tong S*. 2005. Effect of mutating the two cysteines required for HBe antigenicity on hepatitis B virus DNA replication and virion secretion. Virology 332: 216-224.
　　26.Tong S*. 2005. Mechanism of HBV genome variability and replication of HBV mutants (review). J. Clin. Virol. 34 Suppl 1: S134-S138.
　　27.Khan N., Guarnieri M., Ahn S., Li J., Zhou Y., Bang G., Kim K., Wands J., Tong S*. 2004. Modulation of hepatitis B virus secretion by naturally occurring mutations in the S gene. J. Virol. 78: 3262-3270.
　　28.Parekh S., Zoulim F., Ahn S.H., Tsai A., Li J.S., Kawai S., Khan N., Trepo C., Wands J.R., Tong S*. 2003. Genome replication, virion secretion, and e antigen expression of naturally occurring hepatitis B virus core promoter mutants. J. Virol. 77: 6601-6612.
　　29.Ahn S.H., Kramvis A., Kawai S., Spangenberg H., Li J.S., Kimbi G., Kew M., Wands J., Tong S*. 2003. Sequence variation upstream of precore translation initiation codon reduces hepatitis B virus e antigen production. Gastroenterology 125: 1370-1378.
　　30.Spangenberg H.C., Lee H.B., Li J.S., Tan F., Skidgel R., Wands J.R., Tong S*. 2001. A short sequence within domain C of duck carboxypeptidase D is critical for duck hepatitis B virus binding and determines host specificity. J. Virol. 75:10630-10642.
　　31.Tong S.*, Li J.S., Wands J.R. 1999. Carboxypeptidase D is an avian hepatitis B virus receptor. J. Virol. 73: 8696-8702.
　　32.Tong S., Trepo C. 1997. The HBe-minus mutants of hepatitis B virus (book chapter). In The Molecular Medicine of Viral Hepatitis. T.J. Harrison & A.J. Zuckerman (Eds). John Wiley & Sons. pp91-104.
　　33.Tong S., Li J.S., Wands J.R. 1995. Interaction between duck hepatitis B virus and a carboxypeptidase-like protien is mediated through a neutralizing epitope of the pre-S region and occurs during viral infection. J. Virol. 69: 7106-7112.
　　34.Tong S.P.*, Li J.S., Vitvitski L., Kay A., Trepo C. 1993. Evidence for a base-paired region of hepatitis B virus pregenome encapsidation signal which influences the patterns of precore mutations abolishing HBe protein expression. J. Virol. 67: 5651-5655.
　　35.Tong S., Li J.S., Vitvitski L., Trepo C. 1992. Replication capacities of natural and artificial precore stop codon mutants of hepatitis B virus: relevance of pregenome encapsidation signal. Virology 191: 237-245.
　　36.Tong S., Brotman B., Li J., Vitvitski L., Pascal D., Prince A., Trepo C. 1991. In vitro and in vivo replication capacity of the precore region defective hepatitis B virus variants. J. Hepatol. 13 Suppl. 4: s68-s73.
　　37.Tong S., Li J.S., Vitvitski L., Lepot D., Trepo C. 1991. Generation of a 1.5 Kb cDNA fragment of hepatitis C virus genome by overlap extension. J. Med. Virol. 35: 228-231.
　　38.Tong S., Diot C., Gripon P., Li J.S., Vitvitski L., Trepo C., Guguen-Guillouzo C. 1991. In vitro replication competence of a cloned hepatitis B virus variant with a nonsense mutation in the distal pre-C region. Virology 181: 733-737.
　　39.Tong S., Li J.S., Vitvitski L., Benjelloun S., Trepo C. 1991. Rapid screening for bacterial colonies harbouring tandem hepatitis B virus sequences by an oligonucleotide probe. J. Virol. Meth. 32: 109-114.
　　40.Tong S., Li J.S., Vitvitski L., Trepo C. 1990. Active heptitis B virus replication in the presence of anti-HBe is associated with viral variants containing in inactive pre-C region. Virology 176: 596-603.