• 季维智(Weizhi Ji)

    博士生导师,昆明理工大学特聘教授
    灵长类转化医学院 院长
    云南中科灵长类生物医学重点实验室 理事长

    E-mail:wji@lpbr.cn

    一、简历

    现任昆明理工大学灵长类转化医学研究院院长,生物医学动物模型国家地方联合工程研究中心主任,云南省灵长类生物医学动物重点实验室理事长。“国家干细胞研究指导协调委员会”专家,“国家重大科学研究计划生殖与发育专家组”成员(2006-2014),“国家实验动物研究委员会”专家组成员和973项目首席科学家。1982年毕业于云南大学生物系,1995-1997年任美国威斯康星大学动物医学与生物化学系客座教授,1996-2005年任中科院昆明动物研究所所长。现从事灵长类生殖发育生物学和干细胞的研究,其所领导的研究团队在猕猴干细胞和转基因灵长类动物方面获得国际一流的研究成果,使我国在非人灵长类靶向基因修饰的研究,居于世界领先水平。在Cell,Cell Sten Cell, PNAS, Stem Cells,JBC,Biology of Reproduction,Human Reproduction等杂志上发表论文100余篇。

    二、研究成果介绍

    1.猕猴卵母细胞体外成熟和胚胎的早期发育
    季维智研究团队率先开展了优化猕猴超排体系的研究,比较了超排时间、剂量等因素后,建立了猕猴最佳体系,获得了较大数量和高质量的卵母细胞,并提高了动物的使用效率,成为领域内的标准(Theriogenology 2009,72: 243-50;Theriogenology 2008,70(1):108-14;Am J Primatol. 2007,69(11):1278-84)。在此基础上,首次建立并完善了猕猴卵母细胞的无血清培养系统。系统研究了影响卵母细胞成熟和早期胚胎发育中的细胞质因子。发现滤泡内调控卵母细胞成熟的机制及滤泡间相互调控机制的完善与猕猴年龄有关,灵长类动物卵的成熟及发育潜能受年龄影响,猕猴卵母细胞的体外成熟需要激素调控;确定了猕猴卵母细胞成熟的营养物质需求(Human Reproduction,2003,18: 2137-214;Reproduction,2002,124:515-522;Am. J. Primatol. 2001,55: 223-232;Human Reprod.2001,16:300-30;Mol. Reprod. Develop. 2001,58:348-355; Biol. Reprod. 2001, 64: 1417-142. Theriogeology 2000, 54:999-1006;Molecular Reproduction and Development 1994, 39: 25-29;Chinese Science Bulletin 1994,39: 861-865;Perspective in Primate Biology 1992,4: 63-69;Biology of Reproduction 1990, 41: 1024-1033; Endocrinology 1989, 124: 891-898)。

    2.猕猴属动物精子的冷冻保存
    灵长类动物精子的低温保存报道不多也是一个难题。精子的低温保存不仅对灵长类动物的保护有益,而且对生殖生物学的研究提供可靠的物质基础。该团队系统地从渗透剂类型、冷冻速率等方面对多种猕猴属动物开展研究,为研究灵长类动物种质资源的保存提供了理论和实践基础(J Vet Med Sci. 2011, 73(6):717-23; J Reprod Dev. 2011 57:737-43; Am. J. Primatol. 2006, 68: 103-108; Am. J. Primatol. 2006, 68: 39-49; Asian J.Androl.2005, 793): DOI:10.1111/j.1745-7262; J Androl 2005, 26: 387-395; Cell Preservation Technology 2004, 2: 29-33; Am J Primatol. 2004, 62:301-306; Am. J. Primatol. 2003, 59: 159-165; Theriogenology 2002, 58, 1253-1260; Cryobiology 2000, 41:232-240; Theriogenology 1997, 47: 1415-1424)。并对一些胚胎发育的因素做了一系列研究胚胎体外培养体系的建立(Cell Research 2010; doi: 10.1038/cr.2010.7;Cloning and Stem Cells 2007,DOI:10.1089/clo.2007.0040;Reproduction 133:947-54;Biol Reprod 2006, 10.1095/biolreprod.106.051383;Human Reproduction, 21:2564-2571)。

    3.猕猴胚胎干细胞的建立和分化研究
    建立了猕猴胚胎和iPS干细胞,率先发表了一系列干细胞的培养体系的改进、定向诱导分化等方面的有影响的结果(Stem Cells and Development 2013,doi:1089/scd.2013.0280;J Neurosci Res. 2012, 90(7):1382-91;Plos One 2011,Volume 6 | Issue 2 | e17124;Cell Research 2010,doi: 10.1038/cr.2010.7;Reproductive BioMedicine 2009,19: 426-433;Stem Cells 2009,27(8):1954-62;Cell Research 2009,19:268-270;Cell Stem Cell 2008,3:587 – 590;J. Biol. Chem. 2008,283: 35929–35940;Stem Cells 2005,25:481-489;Stem Cells 2007,10: 2004-2008;Stem Cells 2005,23:1192-1199;Archives of Andrology 2003,49: 331-336;World Journal of Gastroenterology 2003 9: 485-490)。

    4.灵长类转基因动物研究
    季维智研究团队早先就是国际上少数能成功进行猕猴转基因的实验室(Niu et al. PNAS, 2010)。季维智领导的团队,与国内有关单位合作成功运用CRISPR和TALEN技术,实现了猕猴、食蟹猴两个物种的靶向基因修饰,使我国在灵长类转基因领域处于国际领先水平。CRISPRA/Cas9研究成果于2014年2月13日在《细胞 Cell》杂志发表(Generation of Gene-Modified Cynomolgus Monkey via Cas9/RNA-Mediated Gene Targeting in One-Cell Embryos, Cell, Volume 156, Issue 4, 836-843),3月6日,TALENs研究结果在《细胞干细胞 Cell Stem Cell》杂志发表(TALEN-Mediated Gene Mutagenesis in Rhesus and Cynomolgus Monkeys,Cell Stem Cell, Volume 14, Issue 3, 323-328)。

    三、近五年相关论文

    1.Niu Y, Shen B, Cui Y, Chen Y, Wang J, Wang L, Kang Y, Zhao X, Si W, Li W, Xiang AP, Zhou J, Guo X, Bi Y, Si C, Hu B, Dong G, Wang H, Zhou Z, Li T, Tan T, Pu X, Wang F, Ji S, Zhou Q, Huang X*, Ji W*, Sha J*. Generation of Gene-Modified Cynomolgus Monkey via Cas9/RNA-Mediated Gene Targeting in One-Cell Embryos. Cell, Volume 156, Issue 4, 836-843, 30 January 2014
    2.Liu H, Chen Y, Niu Y, Zhang K, Kang Y, Ge W, Liu X, Zhao E, Wang C, Lin S, Jing B, Si C, Lin Q, Chen X, Lin H, Pu X, Wang Y, Qin B, Wang F, Wang H, Si W, Zhou J, Tan T, Li T, Ji S, Xue Z, Luo Y, Cheng L, Zhou Q, Li S*, Sun YE*, Ji W*. TALEN-Mediated Gene Mutagenesis in Rhesus and Cynomolgus Monkeys. Cell Stem Cell, Volume 14, Issue 3, 323-328, 13 February 2014
    3.Tan T, Lu B, Zhang J, Niu YY, Si W, Wei Q, Ji WZ 2013 Notch1 Signaling Antagonizes Transforming Growth Factor-β Pathway and Induces Apoptosis in Rabbit Trophoblast Stem Cells. Stem Cells and Development.doi:1089/scd.2013.0280
    4.Chen Y, Niu Y, Ji W. 2012 Transgenic nonhuman primate models for human diseases: approaches and contributing factors. J Genet Genomics. 39(6):247-51.
    5.Chen Y, Niu Y, Yang S, He X, Ji S, Si W, Tang X, Xie Y, Wang H, Lv Y, Zhou Q and Ji W. 2012 The Available Time Window for Embryo Transfer in the Rhesus Monkey (Macaca mulatta). American Journal of Primatology. 74 (2):165–173
    6.Chen Y, Wang Z, Xie Y, Guo X, Tang X, Wang S, Yang S, Chen K, Niu Y, Ji W.2012Folic acid deficiency inhibits neural rosette formation and neuronal differentiation from rhesus monkey embryonic stem cells. J Neurosci Res. 90(7):1382-91
    7.Tn T, Tang X, Zhang J, Niu Y, Chen H, Li B, Wei Q, Ji W. 2011 Generation of trophoblast stem cells from rabbit embryonic stem cells with BMP4. Plos One Volume 6 | Issue 2 | e17124.
    8.Yang S, Ping S, Si W, He X, Wang X, Lu Y, Ji S, Niu Y, Ji W. 2011 Optimization of ethylene glycol concentrations, freezing rates and holding times in liquid nitrogen vapor for cryopreservation of rhesus macaque (Macaca mulatta) sperm. J Vet Med Sci. 73(6):717-23.
    9.Yang S, Ping S, Ji S, Lu Y, Niu Y, Wang H, Ji W, Si W. 2011 The positive effects of seminal plasma during the freezing process on cryosurvival of sperm with poor freezability in the rhesus macaque (Macaca mulatta). J Reprod Dev. 57(6):737-43.
    10.Niu Y, Yu Y, Bernat A, Yang S, He X, Guo X, Chen D, Chen Y, Ji S, Si W, Li Y, Tan T, Wei Q, Wang H, Shi L, Guan J, Zhu X, Afanassieff M, Savatier P, Zhang K, Zhou Q, Ji W. 2010 Transgenic rhesus monkeys produced by gene transfer into early cleavage stage embryos using a simian immunodeficiency virus-based vector. Proc Natl Acad Sci U S A. 12:107(41):17663-7.
    11.Wang Y, Hai T, Liu Z, Zhou S, Lv Z, Ding C, Liu L, Niu Y, Zhao X, Tong M, Wang L, Jouneau A, Zhang X, Ji W, Zhou Q. 2010 HSPC117 deficiency in clonedembryos causes placental abnormality and fetal death. Biochem Biophys Res Commun. 397(3):407-12.
    12.Chen HW, Wei Q, Zhang J, Xu CK, Tan T, Ji WZ 2010 Netrin-1 signaling mediates O-induced glial precursor migration and accumulation. Cell Research advance online publication 19 January 2010; doi: 10.1038/cr.2010.7
    13.Chen X, Li T Li X, Xie Y, Guo X, Ji S, Niu Y, Yu Y, Ding C, Yao R, Yang S, Ji W, Zhou Q 2009 Neural progenitors derived from monkey embryonic stem cells in a simple monoculture system. Reproductive BioMedicine 19: 426-433.
    14.Ren G, Su J, Zhang L, Zhao X, Ling W, L'huillie A, Zhang J, Lu Y, Roberts AI, Ji W, Zhang H, Rabson AB, Shi Y. 2009 Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem Cells. 27(8):1954-62.
    15.Jin LF, Ji SH, Shen Y, Tang XH, Guo XY, Lu YQ, Chen HW, Deng HK, Yan XY, Zhou Q, Ji WZ. 2009 Isolation and characterization of liver epithelial progenitor cells from normal adult rhesus monkeys (Macaca mulatta). Cell Research 19:268-270.
    16.Yang S, He X, Niu Y, Hildebrandt TB, Jewgenow K, Goeritz F, Tang X, Chang Y, Zhou Q, Ji W. 2009 Ovarian response to gonadotropin stimulation in juvenile rhesus monkeys. Theriogenology 72: 243-50.

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