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姓名:夏海滨 

职称/职务:教授

电话:029-85310272

传真:

电子信箱:hbxia2001@163.com

研究方向:

办公地点:

 

一、个人简介

夏海滨,博士,生化与分子生物学教授,博士生导师。现任陕西师范大学基因治疗重点实验室主任。全国生化与分子生物学酶学专业委员会成员;陕西省生物化学与分子生物学学会副理事长;陕西省细胞生物学副理事长;陕西省免疫学会常务理事;美国基因及细胞治疗学会(ASGCT)会员。

19949月至19977月在第四军医大学免疫学教研室攻读博士学位,199711月至20059月在美国University of Iowa基因治疗中心从事有关神经退行性疾病基因治疗研究,20051020068月在美国University of Texas Southwest Medical Center任助理教授,从事骨骼肌干细胞方面的研究。20069月至今,任职陕西师范大学生命科学学院教授, 主要从事肿瘤基因治疗、免疫治疗、基因编辑技术的应用及额颞叶变性分子机制研究等。在腺病毒载体构建、靶向修饰、可控表达及应用方面具有十分丰富的经验。主要科研成就:首次成功用 Pol II 启动子表达具有发夹结构的小干扰RNA,并最早将腺病毒载体用于表达siRNA的研究;首次将腺相关病毒载体表达的siRNA用于神经退行性疾病动物模型的治疗研究,相关研究成果发表在《Nature Medicine》(自然医学)、《Nature Biotechnology》(自然生物工程学杂志)、《PNAS (美国国家科学院院刊)等国际一流刊物。论文SCI引用次数已达2200余次,其中单篇最高SCI引用次数近1000次,相关研究成果获得国际专利3项。在Nature Medicine Nature Biotechnology PNAS Hum Gene Ther Cancer Gene Ther Gene TherapyJ. Virol Plos One J. Biotechnol Int J Oncol等国内外学术刊物上发表论文80余篇。2006年至今,主持国家科技部8631项,国家自然科学基金5项,农业部农业部科技重大专项子课题1项,陕西省自然科学基金重点项目1项;陕西省自然科学基金面上项目1项。申请国内专利16项,已授权专利13项。

 

、承担的科研项目

1. 国家自然科学基金面上项目,“基于双靶分子识别的Dox调控的增强型IL13 CAR-T在恶性脑胶质瘤动物模型中的实验治疗研究” (2018.1-2021.12)。课题编号:81773265

2. 国家自然科学基金面上项目, “结合靶向基因组编辑技术构建用于单基因缺陷原位修复的新型高容量腺病毒载体” (2015.1-2018.12)。课题编号:81471772

3. 陕西省自然科学基金重点项目, “新型溶瘤腺病毒载体靶向恶性脑胶质瘤的基因治疗研究” (2014.1-2016.12)。 课题编号:2014JZ005

4. 国家自然科学基金面上项目,“骨髓间充质干细胞装载新型药物诱导性溶瘤腺病毒Ad5/11-Ind-D24靶向脑胶质母细胞瘤的实验治疗研究”(2013.1-2016.12)。课题编号:81272543

5. 国家自然科学基金面上项目,“腺病毒核心蛋白遗传标记方法的建立及其应用研究”(2011.1-2013.12)。课题编号:31070137

6. 农业部科技重大专项子课题,“锌指核酸酶及同源重组腺病毒表达载体的构建” (2009.6 -2010.12);课题编号:2009ZX08010-023B

7. 国家自然科学基金面上项目,“新型靶向条件复制型溶瘤腺病毒载体Ad5/11 D24 在恶性脑胶质母细胞瘤中的实验治疗研究”(2009.1-2011.12). 课题编号:30872993

8. 陕西省自然科学基金面上项目,“双表达VEGF siRNA 的新型靶向Ad5/3-RGD腺病毒载体在脑胶质母细胞瘤基因治疗中的实验研究”(2008.1.1-2009.12.30;课题编号:2007C201

9. 国家科技部863课题,“高效表达小干扰RNA 新型腺病毒载体的研究”(2006.12.1-2008.12.31);课题编号:2006AA02Z163

 

、代表性论文

1. Zhang JH, Xia HB*. (2019) Lentiviral-Mediated Overexpression of MicroRNA-141 Promotes Cell Proliferation and Inhibits Apoptosis in Human Esophageal Squamous Cell Carcinoma. Recent Pat Anticancer Drug Discov. [Epub ahead of print]

2. Li Y, Wang D, Li Y, Zhu J, Zhao J, Deng Y, Rogalski EJ, Bigio EH, Rademaker AW, Mao Q, Xia H*. (2019) A Highly Sensitive Sandwich ELISA to Detect CSF Progranulin: A Potential Biomarker for CNS Disorders. J Neuropathol Exp Neurol.78(5): 406~415

3. Shan L, Wang D, Mao Q, Xia H*. (2019) Establishment of a DGKθ Endogenous Promoter Luciferase Reporter HepG2 Cell Line for Studying the Transcriptional Regulation of DGKθ Gene. Applied Biochemistry and Biotechnology. 187(4): 1344~1355

4. Li Y, Li S, Li Y, Mao Q, Xia H*. (2019) Generation of a novel HEK293 luciferase reporter cell line by CRISPR/Cas9-mediated site-specific integration in the genome to explore the transcriptional regulation of the PGRN gene. Bioengineered. 10(1): 98~107

5. Chen H, Li Y, Du C, Li Y, Zhao J, Zheng X, Mao Q, Xia H*. (2018) Aptazyme-mediated direct modulation of post-transcriptional sgRNA level for conditional genome editing and gene expression. Journal of Biotechnology. 288: 23~29

6. Li Y, Zhang W, Zhao J, Li S, Shan L, Zhu J, Li Y, Zhu H, Mao Q, Xia H*.(2018) Establishing a dual knock-out cell line by lentivirus based combined CRISPR/Cas9 and Loxp/Cre system. Cytotechnology.70(6): 1595~1605

7. Li Z, Zhao J, Muhammad N, Wang D, Mao Q, Xia H*. (2018) Establishment of a HEK293 cell line by CRISPR/Cas9- mediated luciferase knock-in to study transcriptional regulation of the human SREBP1 gene. Biotechnol Lett. 40: 1495~1506

8. Zhang J, Zhao J, Zheng X, Cai K, Mao Q, Xia H*. (2018) Establishment of a novel hepatic steatosis cell model by Cas9sgRNA-mediated DGKθ gene knockout. MOLECULAR MEDICINE REPORTS. 17: 2169~2176

9. Li Y, Li Y, Ye M, Wang D, Zhao J, Sun X, Mao Q, Xia H*.(2017) Biological function analysis of monoclonal antibodies against human granulins in vitro using U251 cells as a model. Protein Expression and Purification. 130: 55~62

10. Muhammad N, Mao Q,Xia H*. (2017) CAR T-cells for cancer therapy. Biotechnology and Genetic Engineering Reviews. 33(2): 190~226

11. Zhang W, Xiao D, Shan L, Zhao J, Mao Q, Xia H*. (2017) Generation of apoptosis-resistant HEK293 cells with CRISPR/Cas mediated quadruple gene knockout for improved protein and virus production. Biotechnol Bioeng. 114(11): 2539~2549

12. Chen F, Li Y, Zhao J, Mao Q, Xia H*. (2017) Domain-Specific Monoclonal Antibodies Against Human Rev-erbβ. Appl Biochem Biotechnol. 182(3):978-989.

13. Dai X, Li Y, Sun X, Cai K, Mao Q, Xia H*.(2017) Generation of Domain-Specific Monoclonal Antibodies Against Human Glutaredoxin3. Monoclon Antib Immunodiagn Immunother. 35(6):285-292.

14. Li Y, Li Y, Zhao J, Zheng X, Mao Q, Xia H*. (2017) Development of a Sensitive Luciferase-Based Sandwich ELISA System for the Detection of Human Extracellular Matrix 1 Protein. Monoclon Antib Immunodiagn Immunother. 35(6):273-279.

15. Li Y, Li Y, Ye M, Wang D, Zhao J, Sun X, Mao Q, Xia H*.(2017) Biological function analysis of monoclonal antibodies against human granulins in vitro using U251 cells as a model. Protein Expr Purif. 130:55-62.

16. Zheng X, Li Y, Zhao J, Wang D, Xia H*, Mao Q. (2016) Production and Characterization of Monoclonal Antibodies against Human Nuclear Protein FAM76B. PLoS One. 11(3):e0152237.

17. Xiao D, Zhang W, Li Y, Liu K, Zhao J, Sun X, Shan L, Mao Q, Xia H*.(2016) A novel luciferase knock-in reporter system for studying transcriptional regulation of the human Sox2 gene. J Biotechnol.219:110-6.

18. Li Y, Li Y, Zhao J, Wang D, Mao Q, Xia H*. (2016) Production and characterization of domain-specific monoclonal antibodies against human ECM1. Protein Expr Purif. 121:103-111.

19. Wang D, Guo Y, Li Y, Li W, Zheng X, Xia H*, Mao Q.(2015)Detection of CD133 expression in U87 glioblastoma cells using a novel anti-CD133 monoclonal antibody.Oncol Lett. 9(6):2603-2608.

20. Chen H, Wang D, Xia R, Mao Q,Xia H*.(2015) A novel adenoviral vector carrying an all-in-one Tet-On system with an autoregulatory loop for tight, inducible transgene expression.BMC Biotechnol.13;15:4.

21. Zhang W, Chen H, Zheng X, Wang D, Ji H, Xia H*, Mao Q. (2014).Targeted genome correction by a single adenoviral vector simultaneously carrying an inducible zinc finger nuclease and a donor template. J Biotechnol. 2014 Aug 10

22. Wang D, Li W, Zhang H, Mao Q, Xia H*. (2014).A targeting peptide improves adenovirus-mediated transduction of a glioblastoma cell line. Oncol Rep. 31(5):2093-8.

23. Zhang W, Wang D, Liu S, Zheng X, Ji H, Xia H*, Mao Q. (2014). Multiple copies of a linear donor fragment released in situ from a vector improve the efficiency of zinc-finger nuclease-mediated genome editing.Gene Ther. 21(3):282-8.

24. Wang D, Zheng X, Mao Q, Xia H*. (2014). Detection of CD133 expression in U87 glioblastoma cell line using a novel anti-CD133 monoclonal antibody. Oncology Letters (Accepted).

25. Wang L, Liu Q, Li F, Qiu J, Fan H, Ma H, Zhu Y, Wu L, Han X, Yang Z, Jiang H, Wei J, Xia H*. (2013). Apoptosis induced by PGC-1β in breast cancer cells is mediated by the mTOR pathway.Oncol Rep. 30(4):1631-8.

26. Chen H, Zheng X, Di B, Wang D, Zhang Y, Xia H*, Mao Q. (2013) .Aptamer modification improves the adenoviral transduction of malignant glioma cells. J Biotechnol. 168(4):362-6.

27. Li X, Xia R, Zhao J, Wang D, Mao Q, Xia H*. (2013) A one-step ligation system for rapid generation of armed, conditionally-replicating adenoviruses. Biotechnol Lett. 35(8):1215-21.

28. Zhang W, Guo Y, Zhang C, Ji H, Meng W, Wang D, Li X, Mao Q, Xia H*. (2012).Rescue the Failed Half-ZFN by a Sensitive Mammalian Cell-Based Luciferase Reporter System. Plos one 2012;7(9):e45169.

29. Li X, Mao Q, Wang D, Xia H*. (2012). A novel Ad5/11 chimeric oncolytic adenovirus for improved glioma therapy .International Journal of Oncology. 41(6):2159-65.

30. Li X, Mao Q, Wang D, Zhang W, Xia H*2012. A fiber chimeric CRAd vector Ad5/11-D24 double-armed with TRAIL and arresten for enhanced glioblastoma therapy. Hum Gene Ther. 23(6):589-96.

31. Chai L, Liu S, Mao Q, Wang D, Li X, Zheng X, Xia H*2012. A novel conditionally replicating adenoviral vector with dual expression of IL-24 and arresten inserted in E1 and the region between E4 and fiber for improved melanoma therapy. Cancer Gene Ther. 19(4):247-54.

32. Di B, Mao Q, Zhao J, Li X, Wang D, Xia, H*2012. A rapid generation of adenovirus vector with a genetic modification in hexon protein.J. Biotechnol. 157(3):373-378

33. Chai, L, Mao, Q. Wang D., Li, H., Xia, H*. (2011). Domain-specific monoclonal antibodies produced against human PGRN. Hybridoma. 30(3):271-8.

34. Li X, Liu S, Wang D, Chen H, Xia, H*. ( 2011) . Adenoviral delivered eGFP-intron splicing system for multiple gene RNAi. Biotechnol Lett. 33(9):1723-8.

35. Wang, D., Liu, S., Mao, Q., Zhao, J., Xia, H*. (2011). A novel vector for a rapid generation of fiber-mutant adenovirus based on one step ligation and quick screening of positive clones. J. Biotechnol. 152(3):72-6.

36. Zheng, X, Mao, Q, Wang, D, Zhao, J, Xia, H*.( 2011).A novel system for rapid screening of effective siRNA target sites by one step transfection with a single vector. J. Biotechnol. 155(2):135-9.

37. Liu, S., Mao, Q., Zhang, W., Zheng, X., Bian, Y., Wang, D., Li, H., Chai, L., Zhao, J.,Xia, H*. 2009.Genetically modified adenoviral vector with the protein transduction domain of Tat improves gene transfer to CAR-deficient cells. Biosci Rep.

38. Alisky, J.M, Xia, H., Davidson, B.L. (2006). A TAT-modified fusion protein efficiently penetrates mouse hypoglossal nuclei from transduced ependyma. Neurosci Lett. 401:40-3.

39. Xia, H., Mao, Q., Eliason, S.L., Harper, S.Q., Martins, I.H. , Orr, H.T., Paulson, H.L., Yang, L., Kotin, R.M., Davidson, B.L. (2004). RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebeller ataxia. Nat.Med. 10(8): 816-20.

40. Mao, Q., Xia, H., Davidson, B.L. (2003) .Intracellular trafficking of CLN3, the protein underlying the childhood neurodegenerative disease, Batten disease. FEBS Lett. 555 (2):351-7.

41. Mao, Q., Foster, B.J., Xia, H., Davidson, B.L. (2003). Membrane topology of CLN3, the protein underlying Batten disease. FEBS Lett. 541(1-3):40-6.

42. Miller, V.M., Xia, H., Marrs, G.L., Gouvion, C.M., Lee, G., Davidson, B.L. and Paulson, H.L. (2003). Allele-Specific Silencing of Dominant Disease Genes. Proc Natl Acad Sci U S A. 100(12):7195-200.

43. Xia, H., Mao,Q., Henry, Paulson., Davidson, B.L. (2002). siRNA-mediated gene silencing in vitro and in vivo. Nat Biotechnol. 20(10):1006-10.

44. Wang, G., Williams, G., Xia, H., Hickey, M., Shao, J., Davidson, B.L., McCray, P.B.(2002).Apical Barriers to Airway Epithelial Cell Gene Transfer with Amphotropic Retroviral Vector. Gene Ther. 9(14): 922-31.

45. Xia,H., Mao, Q., Davidson, B.L. (2001). The HIV tat protein transduction domain improves the biodistribution of *-glucuronidase expressed from recombinant viral vectors. Nat. Biotechnol. 19(7): 640-4.

46. Anderson, R.D., Haskell, R.E., Xia, H., Roessler, B.J., Davidson., B,L. (2000).A simple method for the rapid generation of recombinant adenoviral vectors. Gene Ther. 7(12): 1034-8.

47. Xia, H., Anderson, B., Mao, Q., Davidson, B.L (2000). Recombinant human adenovirus: targeting to the human transferrin receptor improves gene transfer to brain microcapillary endothelium. J. Virol. 74(23): 11359-66.

 

、授权专利

1. Davidson, Anderson, Haskell and Xia. (2004). Rapid Generation of Recombinant Adenoviral Vectors. US Patent No. US 6830920.

2. Davidson, Xia and Mao. (2005). siRNA-mediated gene silencing with viral vectors. Issuance of Australian Patent No.2005200828.

3. Paulson, Harper, Miller, Davidson, Xia and Mao.(2005). Allele-Specific siRNA-Mediated Gene Silencing. Issuance of Australian Patent No.2005200827.

4. 夏海滨、张伟锋、刘思也。一种基因打靶系统。授权公告日:2015.6.10,专利号:ZL201310157216.4,专利申请国:中国。

5. 夏海滨、张伟锋。锌指蛋白的快速筛选方法。授权公告日:2015.5.27,专利号: ZL201210207952.1,专利申请国:中国。

6. 夏海滨、张伟锋、刘思也。携带锌指核酸酶表达元件和供体DNA的腺病毒及其构建方法和应用。 授权公告日:2014.12.10,专利号:ZL201310076298.X,专利申请国:中国。

7. 夏海滨、陈皓。单载体双向启动的Tet-on诱导表达系统及其构建方法和应用。授权公告日:2014.9.10,专利号:ZL201210300572.2,专利申请国:中国。

8. 夏海滨、李星。纤维蛋白修饰表达两个外源基因的溶瘤腺病毒载体及构建方法和应用。授权公告日:2014.4.23,专利号:ZL201110139756.0,专利申请国:中国。

9. 夏海滨、刘世海。小肽修饰表达两个外源基因的条件复制型溶瘤腺病毒载体及构建方法和应用。授权公告日:2014.3.12,专利号:ZL201110139710.9,专利申请国:中国。

10. 夏海滨、郑晓晶、邸炳艳。制备六联体蛋白经遗传修饰的腺病毒的载体及其构建方法。授权公告日:2014.10.22,专利号:ZL201110427860.X,专利申请国:中国。

11. 夏海滨、李星。一步法构建携带外源基因的D24纤维蛋白修饰的条件复制型腺病毒载体及其应用。授权公告日:2013.9.11,专利号:ZL201210014951.5,专利申请国:中国。

12. 夏海滨、张伟锋。快速检测锌指核酸酶介导基因定点整合的方法。授权公告日: 2013.6.12,专利号:ZL201110009773.2,专利申请国:中国。

13. 夏海滨、赵俊丽。腺病毒核心蛋白遗传标记载体的构建方法。授权公告日: 2012.1.11,专利号:ZL201010214774.6,专利申请国:中国。

14. 夏海滨、张伟锋、郑晓晶、赵俊丽、王东阳。表达小干扰RNAVA1缺失的腺病毒载体的构建方法。授权公告日:2011.5.4,专利号:ZL200910022759.9,专利申请国:中国。

15. 夏海滨、郑晓晶、王东阳、边晔、孙晓聪、冯真真、李婧。小干扰RNA快速筛选的载体及其构建方法和应用。授权公告日:2012.11.7,专利号: ZL200910022909.6,专利申请国:中国。

16. 夏海滨、张伟锋、王东阳、郑晓晶、赵俊丽。肿瘤特异嵌合启动子及其构建方法和应用。授权公告日:2011.11.30,专利号:ZL200910023841.3,专利申请国:中国。