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基本信息:

姓名: 王英杰
职务: PI
职称: 研究员
学历: 博士
专业: 病毒和细胞生物学
所属院系: 浙医一院
研究方向: 细胞增殖与分化;抗病毒机理和新药研发
电话: +86-571-88982345
信箱: yingjiewang@zju.edu.cn
个人主页: http://mypage.zju.edu.cn/yingjiewang

个人简介:

1. 学习经历:

09/1988–06/1992 杭州大学生物系生物工程专业, 获理学学士学位

09/1992–06/1995 杭州大学生物科学与技术系遗传学专业, 获理学硕士学位

06/1997–09/2001 澳大利亚弗林德斯大学医学生化系(Department of Medical Biochemistry, Flinders University),获博士学位(Ph.D.)


2. 工作经历:

07/1995–04/1997 杭州高乐生化制品有限公司, 高级技术员

10/2001–10/2004 美国德州大学西南医学中心生理学系(Department of Physiology, University of Texas Southwestern Medical Center at Dallas),博士后

11/2004–05/2009 美国默克制药公司默克研究所抗病毒研究系(Department of Antiviral Research, Merck Research Laboratories, Merck & Co., Inc.), 资深科学家(Senior Research Biochemist)

06/2009–现在 浙江大学医学院研究员;传染病诊治国家重点实验室PI

05/2012–现在 感染性疾病诊治协同创新中心PI


3. 研究方向:

胞内外信号调控干细胞增殖与分化

核心干性转录因子在肿瘤干细胞中的作用

艾滋病宿主因子作用机理与新药研发


4. 学术成果:

(1)揭示核心干性转录因子Oct4的系列翻译后修饰在多能干细胞和肿瘤干细胞增殖与分化中的作用。发现蛋白激酶Akt可磷酸化最关键的干性转录因子Oct4,Oct4又能以正反馈方式激活AKT基因转录,从而在干细胞自我更新和凋亡之间建立起全新的联系,提出和阐述了多能干细胞中“Akt-Oct4调控通路”的新概念,证明肝癌、脑胶质瘤等肿瘤干细胞中“Akt-Oct4调控通路”被过度激活,是潜在的药物靶标;建立了Oct4重组蛋白的体外翻译后修饰体系,提出了“特定胞内外信号对应蛋白质上特异性翻译后修饰条形码”的假说,证明系列翻译后修饰调控Oct4-Sox2蛋白互作,并协调多能干细胞向中内胚层分化和上皮–间质转化。

(2)揭示氨基酸代谢物和微环境通过Oct4转录水平调节肿瘤干细胞的增殖分化。证实Oct4基因在脑胶质瘤等一系列分化的肿瘤细胞系中低量转录,且其转录水平可被系列小分子化合物显著上调或下调,为Oct4在分化细胞中表达的可塑性提供了明确证据;进一步证明,在脑胶质瘤、肝癌等肿瘤细胞中,内源的色氨酸代谢产物ITE可作为配体激活芳香烃受体AhR,促使AhR结合在Oct4基因的启动子区,抑制Oct4转录。当肿瘤微环境中色氨酸等氨基酸耗竭或高度缺氧等条件导致ITE浓度显著下降时,原先结合的AhR会脱离Oct4启动子,使Oct4表达上调,启动肿瘤干细胞形成。外源加入的ITE可诱导肿瘤干细胞发生分化,显著降低其致瘤能力。

(3)发现了磷酸肌醇信号分子在细胞囊泡运输和细胞增殖中的新功能。首次揭示磷酸肌醇PtdIns(4)P主要分布在人体细胞内的反面高尔基网(TGN)区域,通过直接招募AP1等调控囊泡运输的关键蛋白,促进TGN区囊泡的形成和转运。据此提出了“不同磷酸肌醇可能作为不同细胞器表面特异性标志分子和协同受体”的假说,得到后续实验证据的广泛支持,为抗肿瘤、抗病毒治疗等提供了新型的药物靶标;阐明真核细胞中PIP5KI三种亚型(alpha, beta, gamma)所合成的PtdIns(4,5)P2分别具有调节actin 细胞骨架系统、调节受体介导的细胞内吞和调节细胞内钙信号转导的特异性功能。


5. 代表论文:

Pan X, Cang X, Dan S, Li J, Cheng J, Kang B, Duan X, Shen B, Wang YJ. Site-specific disruption of the Oct4-Sox2 interaction reveals coordinated mesendodermal differentiation and the epithelial to mesenchymal transition. Under revision at Stem Cell Reports.

Cheng J, Li W, Kang B, Zhou Y, Song J, Dan S, Yang Y, Zhang X, Li J, Yin S, Yao H, Zhu C, Yi W, Zhao Q, Xu X, Zheng M, Zheng S, Li L, Shen B, Wang YJ. (2015) Tryptophan derivatives regulate the transcription of Oct4 in stem-like cancer cells. Nature Communications, in press.

Zhao QW, Zhou YW, Li WX, Yang Y, Cheng J, Zhang XQ, Yin SY, Tong Y, He JQ, Kang B, Yao HP, Zheng M, Wang YJ. (2015) Akt-mediated phosphorylation of Oct4 is associated with the proliferation of stem-like cancer cells. Oncology Reports, 33(4): 1621-1629.

Dan S, Kang B, Duan X, Wang YJ. (2015) A cell-free system toward deciphering the post-translational modification barcodes of Oct4 in different cellular contexts. Biochemical and Biophysical Research Communications, 456(3):714-720.

Lin Y, Yang Y, Li W, Chen Q, Li J, Pan X, Zhou L, Liu C, Chen C, He J, Cao H, Yao H, Zheng L, Xu X, Xia Z, Ren J, Xiao L, Li L, Shen B, Zhou H, Wang YJ. (2012) Reciprocal regulation of Akt and Oct4 promotes the self-renewal and survival of embryonal carcinoma cells. Molecular Cell, 48(4):627-640.

Wang YJ, Li WH, Wang J, Xu K, Dong P, Luo X, Yin HL (2004) Critical role of PIP5KIg87 in InsP3-mediated Ca2+ signaling. Journal of Cell Biology, 167(6): 1005-1010.

Wang YJ, Wang J, Sun HQ, Martinez M, Sun YX, Macia E, Kirchhausen T, Albanesi JP, Roth MG, Yin HL (2003) Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi. Cell, 114(3): 299-310.

Padron D, Wang YJ, Yamamoto M, Yin H, Roth MG (2003) Phosphatidylinositol phosphate 5-kinase Ib recruits AP-2 to the plasma membrane and regulates rates of constitutive endocytosis. Journal of Cell Biology, 162(4): 693-701.

Wang YJ, Gregory RB, Barritt GJ (2002) Maintenance of the filamentous actin cytoskeleton is necessary for the activation of store-operated Ca2+ channels, but not other types of plasma-membrane Ca2+ channels, in rat hepatocytes. Biochemical Journal, 363(Pt1): 117-126.

6. 其它论文:

Wang J, Zhou L, Li Z, Zhang T, Liu W, Liu Z, Yuan YC, Su F, Xu L, Wang Y, Zhou X, Xu H, Hua Y, Wang YJ, Zheng L, Teng YE, Shen B. (2015) YY1 suppresses FEN1 over-expression and drug resistance in breast cancer. BMC Cancer, 15:50.

Su T, Dan S, Wang Y. (2014) Akt–Oct4 regulatory circuit in pluripotent stem cells. Chinese Science Bulletin, 59(10):936-943.

Cao H, Ma J, Yang J, Su X, Chen D, Yu J, Pan Q, Shao L, Zhou P, Li J, Wang Y, Li L. (2014) A metabonomics study of Chinese miniature pigs with acute liver failure treated with transplantation of placental mesenchymal stem cells. Metabolomics, 10(4):651-662.

Wang A, Chen F, Wang Y, Shen M, Xu Y, Hu J, Wang S, Geng F, Wang C, Ran X, Su Y, Cheng T, Wang J. (2013) Enhancement of Antiviral Activity of Human Alpha-defensin 5 against Herpes Simplex Virus Type 2 by Arginine Mutagenesis at Adaptive Evolution Sites. Journal of Virology, 87(5):2835-2845.

Yang Y, Li J, Pan X, Zhou P, Yu X, Cao H, Wang Y, Li L. (2013) Co-culture with mesenchymal stem cells enhances metabolic functions of liver cells in bioartificial liver system. Biotechnology & Bioengineering, 110(3):958-968.

Yang H, Liu C, Jamsen J, Wu Z, Wang Y, Chen J, Zheng L, Shen B. (2012) The DNase domain-containing protein TATDN1 plays an important role in chromosomal segregation and cell cycle progression during zebrafish eye development. Cell Cycle, 11(24):4626-4632.

Draz MS, Fang BA, Li L, Chen Z, Wang Y, Xu Y, Yang J, Killeen K, Chen FF. (2012) Hybrid nanocluster plasmonic resonator for immunological detection of hepatitis B virus. ACS Nano, 6(9):7634-7643.

Guo Z, Kanjanapangka J, Liu N, Liu S, Liu C, Wu Z, Wang Y, Loh T, Kowolik C, Jamsen J, Zhou M, Truong K, Chen Y, Zheng L, Shen B. (2012) Sequential posttranslational modifications program FEN1 degradation during cell-cycle progression. Molecular Cell, 47(3):444-456.

Yu J, Cao H, Yang J, Pan Q, Ma J, Li J, Li Y, Li J, Wang Y, Li L. (2012) In vivo hepatic differentiation of mesenchymal stem cells from human umbilical cord blood after transplantation into mice with liver injury. Biochemical and Biophysical Research Communications, 422(4):539-545.

Cao H, Yang J, Yu J, Pan Q, Li J, Zhou P, Li Y, Li J, Wang Y, Li L. (2012) Therapeutic potential of transplanted placental mesenchymal stem cells in treating Chinese miniature pigs with acute liver failure. BMC Medicine, 10:56.

Lu M, Felock PJ, Munshi V, Hrin RC, Wang YJ, Yan Y, Munshi S, McGaughey GB, Gomez R, Anthony NJ, Williams TM, Grobler JA, Hazuda DJ, McKenna PM, Miller MD, Lai MT. (2012) Antiviral activity and in vitro mutation development pathways of MK-6186, a novel nonnucleoside reverse transcriptase inhibitor. Antimicrobial Agents and Chemotherapy, 56(6):3324-3335.

Caulfield MJ, Dudkin VY, Ottinger EA, Getty KL, Zuck PD, Kaufhold RM, Hepler RW, McGaughey GB, Citron M, Hrin RC, Wang YJ, Miller MD, Joyce JG. (2010)Small molecule mimetics of an HIV-1 gp41 fusion intermediate as vaccine leads. Journal of Biological Chemistry, 285(52):40604-40611.

Lai MT, Lu M, Felock PJ, Hrin RC,1 Wang YJ, Yan Y, Munshi S, McGaughey GB, Tynebor RM, Tucker TJ, Williams TM, Grobler JA, Hazuda DJ, McKenna PM, Miller MD. (2010) Distinct mutation pathways of non-subtype B HIV-1 during in vitro resistance selection with non-nucleoside reverse transcriptase inhibitors. Antimicrobial Agents and Chemotherapy, 54(11):4812-4824.

Wang YJ, McKenna PM, Hrin R, Felock P, Lu M, Jones KG, Coburn CA, Grobler JA, Hazuda DJ, Miller MD, Lai MT. (2010) Assessment of the susceptibility of mutant HIV-1 to antiviral agents. Journal of Virological Methods, 165(2):230-237.

Cao H, Yu J, Xu W, Jia X, Yang J, Pan Q, Zhang Q, Sheng G, Li J, Pan X, Wang Y, Li L. (2009) Proteomic analysis of regenerating mouse liver following 50% partial hepatectomy. Proteome Science, 7:48.

Montgomery DL, Wang YJ, Hrin R, Luftig M, Su B, Miller MD, Wang F, Haytko P, Huang L, Vitelli S, Condra J, Liu X, Hampton R, Carfi A, Pessi A, Bianchi E, Joyce J, Lloyd C, Geleziunas R, Bramhill D, King VM, Finnefrock A, Strohl W, An Z (2009) Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41. MAbs, 1(5):462-474.

Ingallinella P, Bianchi E, Ladwa NA, Wang YJ, Hrin R, Bonelli F, Ketas TJ, Moore JP, Miller MD, Pessi A (2009) Addition of a cholesterol group to an HIV-1 peptide fusion inhibitor dramatically increases its antiviral potency. Proc Natl Acad Sci USA, 106(14): 5801-5806.

Hrin R, Montgomery DL, Wang F, Condra JH, An Z, Strohl WR, Bianchi E, Pessi A, Joyce JG, Wang YJ (2008) In vitro synergy between peptides or neutralizing antibodies targeting the N- and C-terminal heptad repeats of HIV-1 gp41. AIDS Research and Human Retroviruses, 24(12): 1537-1544.

Su B, Hrin R, Harvey BR, Wang YJ, Ernst RE, Hampton RA, Miller MD, Strohl WR, An Z, Montgomery DL (2007) Automated high-throughput purification of antibody fragments to facilitate evaluation in functional and kinetic based assays. Journal of Immunological Methods, 322(1-2): 94-103.

Pizarro-Cerda J, Payrastre B, Wang YJ, Veiga E, Yin HL, Cossart P (2007) Type II phosphatidylinositol 4-kinases promote Listeria monocytogenes entry into target cells. Cellular Microbiology, 9(10): 2381-2390.

Yamamoto M, Chen MZ, Wang YJ, Sun HQ, Wei Y, Martinez M, Yin HL (2006) Hypertonic stress increases phosphatidylinositol 4,5-bisphosphate levels by activating PIP5KIb. Journal of Biological Chemistry, 281(43): 32630-32638.

Wang YJ, Gregory RB, Barritt GJ (2000) Regulation of F-actin and endoplasmic reticulum organisation by the trimeric G-protein Gi2 in rat hepatocytes: implication for the activation of store-operated Ca2+ inflow. Journal of Biological Chemistry, 275(29): 22229-22237.

Auld A, Chen J, Brereton HM, Wang YJ, Gregory RB, Barritt GJ (2000) Store-operated Ca2+ inflow in Reuber hepatoma cells is inhibited by voltage-operated Ca2+ channel antagonists and, in contrast to freshly isolated hepatocytes, does not require a pertussis toxin-sensitive trimeric GTP-binding protein. Biochimica et Biophysica Acta - Molecular Cell Research, 1497(1):11-26.


7. 主要获奖:

2013年度国家科技进步一等奖(排名第5)
2012年度浙江大学“十大学术进展”


8. 科研项目:

国家自然科学基金面上项目#81472722 (项目主持人)
国家自然科学基金面上项目#31271465 (项目主持人)
863计划主题项目“间充质干细胞的基础与应用研究”子课题 #2011AA020118(项目骨干)
浙江省杰出青年科学基金项目#R2100226 (项目主持人)
传染病诊治国家重点实验室自主课题 #A61003-11(项目主持人)
传染病诊治国家重点实验室自主课题 #A60903-4 (项目共同主持人)
美国白血病和淋巴瘤学会学术发展研究基金项目 (Leukemia & Lymphoma Society Career Development Grant) # 5051-04 (项目主持人)
美国NIH 基金项目 NIH-R01-GM066110 (项目主要参与者)
美国NIH 基金项目 NIH-5R01-GM51112 (项目参与者)
美国NIH 基金项目 NIH-5R01-GM061203 (项目参与者)