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费 俭
来源:  作者:  发表时间:2011-11-25  阅读次数:25024次

姓       名: 费  俭

所属部门:模式生物技术开放实验室

学         位:博士

导师情况:博士生导师

研究领域:分子生物学

研究方向:基因功能的模式生物研究

      E-mail Jfei@tongji.edu.cn

联系电话:65980334

通讯地址:上海市四平路1239号,同济大学生命科学与技术学院(200092)

研究组长简介
    费俭,1965年出生,获华东理工大学学士和硕士学位、中国科学院上海细胞生物学研究所博士学位,现任同济大学生命科学与技术学院教授,上海南方模式生物研究中心研究员、副主任。1988年7月-2007年2月任职于中科院上海细胞生物学研究所(现为生物化学与细胞生物学研究所),历任研究实习员、助理研究员、副研究员、研究员,中科院上海生命科学研究院模式生物研究中心主任。

 

主要研究方向:

    我们研究小组主要利用小鼠、线虫等模式生物以及遗传操作的手段来研究人类基因以及组织成体干细胞在体内的生理功能,揭示这些基因和细胞在疾病过程的作用。我们尤其关注这些基因或者细胞在决定和影响学习记忆、免疫调节、组织再生、寿命等正常生命活动中的作用,也关心它们和肿瘤的发生发展、神经系统疾病、自身免疫性疾病、代谢性疾病等的关系。利用这些模式生物我们也对药物,包括中药开展研究,以揭示这些药物的作用机制。这些研究给我们带来了很大的乐趣,满足了我们对生命现象的好奇。当然,更为重要的是通过这些研究,可以帮助我们找到新的疾病诊疗方法。

    在过去的一些年中,我们对GABA转运蛋白亚型1(GAT1)基因的功能开展了系统的研究,结果表明,GAT1参与多种生理和病理过程,包括痛觉的调节、酒精和毒品成瘾、学习与记忆、情绪、免疫调节、神经内分泌等,这些研究为GAT1成为一个抗抑郁、镇痛和调节免疫功能的药物作用靶点提供了重要的实验依据。对GAT1以及这个家族中的其他亚型基因的研究已成为我们研究组一个重要的研究方向。

    我们建立了神经元限制性沉默因子(NRSF/REST)条件性基因剔除的小鼠。NRSF被认为通过调节表观遗传修饰参与神经系统和心血管系统的发育,近年来发现它参与了更广泛的生理和病理过程。利用我们建立的条件性剔除小鼠模型,已发现该基因在神经细胞的损伤、癫痫的发生等过程中扮演重要角色,我们对其深入的研究还将揭示出该基因更多的精彩故事。

    人类基因组中编码可以分泌到胞外的蛋白最具有发展成基因工程药物的潜力。我们分析并选择了一批功能未知并推测为分泌蛋白的人鼠同源基因,建立了35种不同基因的剔除小鼠。通过分析这些遗传修饰小鼠的表型变化,获得相关突变基因的功能信息,并将基因功能直接和疾病进行关联,从而可以评估这一基因成为药物的可能性,为发现新的基因工程药物奠定基础。我们已从中发现了和肥胖、雄性生殖等相关的基因,进一步的分析还将发现更多有重要价值的基因功能。

    我们最近利用细胞遗传标记技术对小鼠不同组织干细胞进行遗传标记,并对这些细胞的命运进行追踪,以研究组织干细胞的存在形式、自我更新以及分化去向。这些研究将回答在正常生理或异常病理条件下,不同组织干细胞在其中的参与方式、参与程度和所扮演的角色。 

 

最近发表的论文

1. Shi J, Cai Y, Liu G, Gong N, Liu Z, Xu T, Wang Z, Fei J*. Enhanced learning and memory in GAT1 heterozygous mice. Acta Biochim Biophys Sin (Shanghai). 2012 Feb 7. [Epub ahead of print] PubMed PMID: 22318715.

2. Sun RL, Wang HY, Yang XY, Sheng ZJ, Li LM, Wang L, Wang ZG, Fei J*. Resistance to lipopolysaccharide-induced endotoxic shock in heterozygous Zfp191 gene-knockout mice. Genet Mol Res. 2011 Dec 8;10(4). [Epub ahead of print] PubMed PMID: 22183946.

3. Zhang LL, Wang JJ, Liu Y, Lu XB, Kuang Y, Wan YH, Chen Y, Yan HM, Fei J, Wang ZG. GPR26-deficient mice display increased anxiety- and depression-like behaviors accompanied by reduced phosphorylated cyclic AMP responsive element-binding protein level in central amygdala. Neuroscience. 2011 Nov 24;196:203-14. Epub 2011 Sep 8. PubMed PMID: 21924326.

4. Hu XL, Cheng X, Fei J*, Xiong ZQ. Neuron-restrictive silencer factor is not required for the antiepileptic effect of the ketogenic diet. Epilepsia. 2011 Sep;52(9):1609-16. doi: 10.1111/j.1528-1167.2011.03171.x. Epub 2011 Jul 18. PubMed PMID: 21762439.

5. Wang Q, Xu X, Li J, Liu J, Gu H, Zhang R, Chen J, Kuang Y, Fei J, Jiang C, Wang P, Pei D, Ding S, Xie X. Lithium, an anti-psychotic drug, greatly enhances the generation of induced pluripotent stem cells. Cell Res. 2011 Oct;21(10):1424-35. doi: 10.1038/cr.2011.108. Epub 2011 Jul 5. PubMed PMID:21727907; PubMed Central PMCID: PMC3193456.

6. Qiao Q, Li T, Sun J, Liu X, Ren J, Fei J. Metabolomic analysis of normal (C57BL/6J, 129S1/SvImJ) mice by gas chromatography-mass spectrometry: detection of strain and gender differences. Talanta. 2011 Jul 15;85(1):718-24. Epub 2011 May 5. PubMed PMID: 21645764.

7. Li Y, Yi H, Yao Y, Liao X, Xie Y, Yang J, Yan Z, Wang L, Lu S, Kuang Y, Gu M, Fei J, Wang Z, Huang L. The cytoplasmic domain of MUC1 induces hyperplasia in the mammary gland and correlates with nuclear accumulation of β-catenin. PLoS One. 2011 Apr 20;6(4):e19102. PubMed PMID: 21533058; PubMed Central PMCID: PMC3080410.

8. Sun R, Shen R, Li J, Xu G, Chi J, Li L, Ren J, Wang Z, Fei J*. Lyzl4, a novel mouse sperm-related protein, is involved in fertilization. Acta Biochim Biophys Sin (Shanghai). 2011 May;43(5):346-53. Epub 2011 Mar 28. PubMed PMID: 21444326.

9. Cai L, Bian M, Liu M, Sheng Z, Suo H, Wang Z, Huang F, Fei J*. Ethanol-induced neurodegeneration in NRSF/REST neuronal conditional knockout mice. Neuroscience. 2011 May 5;181:196-205. Epub 2011 Mar 10. PubMed PMID: 21396985.

10. Hu XL, Cheng X, Cai L, Tan GH, Xu L, Feng XY, Lu TJ, Xiong H, Fei J, Xiong ZQ. Conditional deletion of NRSF in forebrain neurons accelerates epileptogenesis in the kindling model. Cereb Cortex. 2011 Sep;21(9):2158-65. Epub 2011 Feb 21. PubMed PMID: 21339379.

11. Ren J, Chen Z, Zhang W, Li L, Sun R, Deng C, Fei Z, Sheng Z, Wang L, Sun X, Wang Z, Fei J*. Increased fat mass and insulin resistance in mice lacking pancreatic lipase-related protein 1. J Nutr Biochem. 2011 Jul;22(7):691-8. Epub 2010 Nov 5. PubMed PMID: 21115337.

12. Liang M, Yang JL, Bian MJ, Liu J, Hong XQ, Wang YC, Huang YF, Gu SP, Yu M, Huang F, Fei J*. Requirement of regulated endocrine-specific protein-18 for development and expression of regulated endocrine-specific protein-18 isoform c in mice. Mol Biol Rep. 2011 Apr;38(4):2557-62. Epub 2010 Nov 21. PubMed PMID: 21104147.

13. Hu J, Fei J, Reutter W, Fan H. Involvement of sialic acid in the regulation of γ--aminobutyric acid uptake activity of γ-aminobutyric acid transporter 1. Glycobiology. 2011 Mar;21(3):329-39. Epub 2010 Nov 2. PubMed PMID: 21045010.

14. Liu XS, Zhao XD, Wang X, Yao YX, Zhang LL, Shu RZ, Ren WH, Huang Y, Huang L, Gu MM, Kuang Y, Wang L, Lu SY, Chi J, Fen JS, Wang YF, Fei J, Dai W, Wang ZG. Germinal Cell Aplasia in Kif18a Mutant Male Mice Due to Impaired Chromosome Congression and Dysregulated BubR1 and CENP-E. Genes Cancer. 2010 Jan;1(1):26-39. PubMed PMID: 20981276; PubMed Central PMCID: PMC2963078.

15. Liu P, Nie S, Li B, Yang ZQ, Xu ZM, Fei J, Lin C, Zeng R, Xu GL. Deficiency in a glutamine-specific methyltransferase for release factor causes mouse embryonic lethality. Mol Cell Biol. 2010 Sep;30(17):4245-53. Epub 2010 Jul 6. PubMed PMID: 20606008; PubMed Central PMCID: PMC2937546.

16. Yao M, Niu G, Sheng Z, Wang Z, Fei J*. Identification of a Smad4/YY1-recognized and BMP2-responsive transcriptional regulatory module in the promoter of mouse GABA transporter subtype I (Gat1) gene. J Neurosci. 2010 Mar 17;30(11):4062-71. PubMed PMID: 20237276.

17. Kuang Y, Wang J, Lu X, Lu S, Zhang L, Shen C, Fei J, Wang Z. [Generation of factor VIII gene knockout mouse by tetraploid embryo complementation technology]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010 Feb;27(1):1-6. Chinese. PubMed PMID: 20140858.

18. Gong N, Li Y, Cai GQ, Niu RF, Fang Q, Wu K, Chen Z, Lin LN, Xu L, Fei J, Xu TL. GABA transporter-1 activity modulates hippocampal theta oscillation and theta burst stimulation-induced long-term potentiation. J Neurosci. 2009 Dec 16;29(50):15836-45. PubMed PMID: 20016099.

19. Liu Z, Liu M, Niu G, Cheng Y, Fei J*. Genome-wide identification of target genes repressed by the zinc finger transcription factor REST/NRSF in the HEK 293 cell line. Acta Biochim Biophys Sin (Shanghai). 2009 Dec;41(12):1008-17. PubMed PMID: 20011975.

20. Wang Y, Luo Q, Xu Y, Feng D, Fei J, Cheng Q, Xu L. Gamma-aminobutyric acid transporter 1 negatively regulates T cell activation and survival through protein kinase C-dependent signaling pathways. J Immunol. 2009 Sep 1;183(5):3488-95. Epub 2009 Aug 10. PubMed PMID: 19667098.

21. Deng T, Kuang Y, Wang L, Li J, Wang Z, Fei J*. An essential role for DNA methyltransferase 3a in melanoma tumorigenesis. Biochem Biophys Res Commun. 2009 Sep 25;387(3):611-6. Epub 2009 Jul 24. PubMed PMID: 19632198.

22. Bian MJ, Li LM, Yu M, Fei J*, Huang F. Elevated interleukin-1beta induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine aggravating dopaminergic neurodegeneration in old male mice. Brain Res. 2009 Dec 11;1302:256-64. Epub 2009 Jul 23. PubMed PMID: 19631617.

23. Yu M, Cai L, Liang M, Huang Y, Gao H, Lu S, Fei J, Huang F. Alteration of NRSF expression exacerbating 1-methyl-4-phenyl-pyridinium ion-induced cell death of SH-SY5Y cells. Neurosci Res. 2009 Nov;65(3):236-44. Epub 2009 Jul 22. PubMed PMID: 19631241.

24. Wu XL, Gu MM, Huang L, Liu XS, Zhang HX, Ding XY, Xu JQ, Cui B, Wang L, Lu SY, Chen XY, Zhang HG, Huang W, Yuan WT, Yang JM, Gu Q, Fei J, Chen Z, Yuan ZM, Wang ZG. Multiple synostoses syndrome is due to a missense mutation in exon 2 of FGF9 gene. Am J Hum Genet. 2009 Jul;85(1):53-63. PubMed PMID: 19589401; PubMed Central PMCID: PMC2706969.

25. Zhang F, Shu R, Wu X, Zhao X, Feng D, Wang L, Lu S, Liu Q, Xiang Y, Fei J, Huang L, Wang Z. Delayed liver injury and impaired hepatocyte proliferation after carbon tetrachloride exposure in BPOZ2-deficient mice. Toxicol Lett. 2009 Aug 10;188(3):201-7. Epub 2009 Apr 23. PubMed PMID: 19393728.

26. Wang Y, Feng D, Liu G, Luo Q, Xu Y, Lin S, Fei J*, Xu L. Gamma-aminobutyric acid transporter 1 negatively regulates T cell-mediated immune responses and ameliorates autoimmune inflammation in the CNS. J Immunol. 2008 Dec 15;181(12):8226-36. Erratum in: J Immunol. 2009 Feb 1;182(3):1772. PubMed PMID: 19050239.

 

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