溶瘤病毒研究组

(一)本组简介

本组主要负责人为黄承浩副教授,现有博士后1名,博士生5名,准博士1名。硕士8名,技术员2名。主要从事肿瘤治疗领域的相关研究,拥有成熟的相关研究技术平台。涉及生物学、临床医学、公共卫生等多个学科领域。

本组致力于开发新型肿瘤治疗药物和开展肿瘤治疗性新靶点的研究,具体研究内容主要包括:

  1. 溶瘤病毒抗肿瘤机制的探究;

  2. 新型溶瘤病毒的研发;

  3. 肿瘤治疗性新靶点的研究。

在前期的研究中,积累了丰富的异位移植瘤模型和原位移植瘤模型,并构建了在肿瘤治疗性药物临床前评价和相关机制探究中有极重要价值的多癌种的病人来源的异种移植肿瘤(patient-derived xenografts, PDX)库,开发了多种类的基因工程肿瘤模型小鼠,在肿瘤的发病机制和肿瘤治疗药物的评估和机制探究方面积累了丰富的实验动物资源和相关技术平台。

在探究肿瘤治疗性新靶标研究中,开发构建了一系列从靶标发现、功能筛选到药效评估的成熟技术平台,在靶标的功能评估和相关药物开发方面积累了丰富的经验和技术。

本组已经研发出了一系列肿瘤选择性高、安全性好、溶瘤活性强和具有多重抗肿瘤免疫调节活性的HSV-1型溶瘤病毒。目前溶瘤病毒株YST-OVH已通过国家药监局的临床试验审批,用于试验性治疗可进行瘤内注射、静脉滴注或胸/腹腔局部给药的多种恶性肿瘤,目前正在开展I期临床试验,有望造福更多的肿瘤患者。在溶瘤病毒研究方面拥有全链条的溶瘤病毒开发,评估和转化研究平台。

(二)导师

黄承浩,博士,副教授。Email: huangchenghao@xmu.edu.cn

(三)正在开展的项目

  1. 新型溶瘤病毒的研发;

  2. 溶瘤病毒抗肿瘤机制探究;

  3. 溶瘤病毒协同增效策略的探究;

  4. 新一代肿瘤细胞模型和动物模型的构建;

  5. 肿瘤治疗性新靶点的开发;

  6. 肿瘤治疗性新靶点相关药物的研究。

(四)近5年来发表的部分文章

  1. Lin, C.#, Ren, W.#, Luo, Y., Li, S., Chang, Y., Li, L., Xiong, D., Huang, X., Xu, Z., Yu, Z., Wang, Y., Zhang, J., Huang, C.* and Xia, N.* Intratumoral Delivery of a PD-1-blocking scFv encoded in Oncolytic HSV-1 Promotes Antitumor Immunity and Synergizes with TIGIT Blockade. Cancer Immunol Res, doi:10.1158/2326-6066.CIR-19-0628 (2020). (*Co-correspondence)

  2. Luo, Y.#, Lin, C.#, Zou, Y., Ju, F., Ren, W., Lin, Y., Wang, Y., Huang, X., Liu, H., Yu, Z., Liu, P., Tan, G., Yuan, Q., Zhang, J., Huang, C.* and Xia, N.* Tumor-targeting oncolytic virus elicits potent immunotherapeutic vaccine responses to tumor antigens. Oncoimmunology 9, 1726168, doi:10.1080/2162402X.2020. 1726168 (2020). (*Co-correspondence)

  3. Lin, M.#, Huang, C. #, Ren, W., Chen, J., Xia, N. and Zhong, S. Mitogen- and Stress-Activated Protein Kinase 1 Mediates Alcohol-Upregulated Transcription of Brf1 and tRNA Genes to Cause Phenotypic Alteration. Oxid Med Cell Longev, 2067959, doi:10.1155/2020/2067959 (2020). (#Co-first author)

  4. Luo, Y.#, Lin, C.#, Ren, W., Ju, F., Xu, Z., Liu, H., Yu, Z., Chen, J., Zhang, J., Liu, P.*, Huang, C.* and Xia, N. Intravenous Injections of a Rationally Selected Oncolytic Herpes Virus as a Potent Virotherapy for Hepatocellular Carcinoma. Mol Ther Oncolytics 15, 153-165, doi:10.1016/j.omto.2019.09.004 (2019). (*Co-correspondence)

  5. Huang, C., Zhang, Y. and Zhong, S. Alcohol Intake and Abnormal Expression of Brf1 in Breast Cancer. Oxidative Medicine and Cellular Longevity 2019, 1-9, doi:10.1155/2019/4818106 (2019).

  6. Zhang, T. Y., Chen, H. Y., Cao, J. L., Xiong, H. L., Mo, X. B., Li, T. L., Kang, X. Z., Zhao, J. H., Yin, B., Zhao, X., Huang, C. H., Yuan, Q., Xue, D., Xia, N. S. and Yuan, Y. A. Structural and functional analyses of hepatitis B virus X protein BH3-like domain and Bcl-xL interaction. Nat Commun 10, 3192, doi:10.1038/s41467-019-11173-1 (2019).

  7. Zou, Y., Luo, Y., Zhang, J., Xia, N., Tan, G. and Huang, C. Bibliometric analysis of oncolytic virus research, 2000 to 2018. Medicine (Baltimore) 98, e16817, doi:10.1097/MD.0000000000016817 (2019).

  8. He, C., Qiu, Y., Han, P., Chen, Y., Zhang, L., Yuan, Q., Zhang, T., Cheng, T., Yuan, L., Huang, C., Zhang, S., Yin, Z., Peng, X. E., Liang, D., Lin, X., Lin, Y., Lin, Z. and Xia, N. ER stress regulating protein phosphatase 2A-B56gamma, targeted by hepatitis B virus X protein, induces cell cycle arrest and apoptosis of hepatocytes. Cell Death Dis 9, 762, doi:10.1038/s41419-018-0787-3 (2018).

  9. Chen, Q., Qiu, S., Li, H., Lin, C., Luo, Y., Ren, W., Zou, Y., Wang, Y., Xia, N. and Huang, C. A novel approach for rapid high-throughput selection of recombinant functional rat monoclonal antibodies. BMC Immunol 19, 35, doi:10.1186/s12865-018-0274-8 (2018).

  10. Yi, Y.#, Huang, C.#, Zhang, Y., Tian, S., Lei, J., Chen, S., Shi, G., Wu, Z., Xia, N. and Zhong, S. Exploring a common mechanism of alcohol-induced deregulation of RNA Pol III genes in liver and breast cells. Gene 626, 309-318, doi:10.1016/j.gene.2017.05.048 (2017). (#Co-first author)

  11. Luo, Y.#, Xiong, D.#, Li, H. H., Qiu, S. P., Lin, C. L., Chen, Q., Huang, C. H.*, Yuan, Q., Zhang, J. and Xia, N. S.* Development of an HSV-1 neutralization test with a glycoprotein D specific antibody for measurement of neutralizing antibody titer in human sera. Virol J 13, 44, doi:10.1186/s12985-016-0508-4 (2016). (*Co-correspondence)

  12. Lin, C., Li, H., Hao, M., Xiong, D., Luo, Y., Huang, C.*, Yuan, Q., Zhang, J. and Xia, N.* Increasing the Efficiency of CRISPR/Cas9-mediated Precise Genome Editing of HSV-1 Virus in Human Cells. Sci Rep 6, 34531, doi:10.1038/srep34531 (2016). (*Co-correspondence)

  13. Yuan, Q., Song, L. W., Liu, C. J., Li, Z., Liu, P. G., Huang, C. H., Yan, Y., Ge, S. X., Wang, Y. B., Peng, C. Y., Zhang, J., Kao, J. H., Chen, D. S., Chen, P. J. and Xia, N. S. Quantitative hepatitis B core antibody level may help predict treatment response in chronic hepatitis B patients. Gut 62, 182-184, doi:10.1136/gutjnl-2012-302656 (2013).

  14. Huang, C. H.#, Yuan, Q.#, Chen, P. J., Zhang, Y. L., Chen, C. R., Zheng, Q. B., Yeh, S. H., Yu, H., Xue, Y., Chen, Y. X., Liu, P. G., Ge, S. X., Zhang, J. and Xia, N. S. Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors. J Hepatol 57, 720-729, doi:10.1016/j.jhep.2012.05.009 (2012).

  15. Geng, X.#, Huang, C.#, Qin, Y., McCombs, J. E., Yuan, Q., Harry, B. L., Palmer, A. E., Xia, N. S. and Xue, D. Hepatitis B virus X protein targets Bcl-2 proteins to increase intracellular calcium, required for virus replication and cell death induction. Proc Natl Acad Sci U S A 109, 18471-18476, doi:10.1073/pnas.1204668109 (2012). (#Co-first author)

  16. Yuan, Q., Ou, S. H., Chen, C. R., Ge, S. X., Pei, B., Chen, Q. R., Yan, Q., Lin, Y. C., Ni, H. Y., Huang, C. H., Yeo, A. E., Shih, J. W., Zhang, J. and Xia, N. S. Molecular characteristics of occult hepatitis B virus from blood donors in southeast China. J Clin Microbiol 48, 357-362, doi:10.1128/JCM.01781-09 (2010).

(五)本组优势

本组围绕多种恶性肿瘤致力于开展肿瘤创新靶点的研究和研发肿瘤治疗药物,与国内外高校、医院及生物医药企业建立了广泛合作,拥有丰富的肿瘤生物治疗研究的平台和经验,学生有机会学习到相关药物从基础研究到应用转化过程中系统全面的知识和技术,可培养学生全面的能力。优秀者可在研究生二年级申请硕博连读;因本课题组所研究项目具有重要临床转化价值与知名企业对接,优秀者也可推荐其就业。

(六)招生条件

主要对口本科专业:生物学(含生物信息学)、公共卫生与预防医学、临床检验诊断学、药学等,其他专业可邮件咨询。

国家传染病诊断试剂与疫苗工程技术研究中心(厦门大学)  地址:中国福建省厦门市翔安区翔安南路厦门大学翔安校区
电话:0592-2183111 传真:0592-2181258  邮编:361102
ICP备案号:D200327