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  • 劉林

    劉林(南開教授)

    劉林,教授,博士生導師,國家杰出青年基金獲得者,南開大學生命科學學院副院長。

    劉林教授團隊通過完全化學小分子的方法,將卵巢顆粒細胞重編程為具有生殖系轉移能力的誘導性多能干細胞,進而分化為卵子,并通過正常受精獲得了健康小鼠。該突破屬世界首次,為保持生育能力、調節(jié)機體內分泌等研究開辟了新思路。


    人物經(jīng)歷

    1993年北京農(nóng)業(yè)大學(現(xiàn)中國農(nóng)業(yè)大學)獲動物生殖學與生物技術博士學位。1994年至1998年分別在英國劍橋Babraham研究所、美國康奈爾大學,康州大學進行博士后和訪問學者研究。1998年至2004年,在美國布朗大學婦產(chǎn)科系生殖醫(yī)學實驗室,任研究員、助理教授。1998年至2009年,美國海洋生物學實驗室(MBL)兼職研究員。2005年獲得國家杰出青年基金資助,2007 年被聘為南開大學生命科學院特聘教授, 兼副院長。

    研究方向

    在發(fā)育生物學和生殖生物技術領域,尤其是在最終能造福人類健康的胚胎工程和再生醫(yī)學領域,進行基礎科學及生物醫(yī)學應用方面的研究:1)哺乳動物卵子老齡化、早期胚胎發(fā)育分子機制與技術工程研究;2)特異多能性干細胞端粒功能及重編程和轉基因研究。

    科研項目

    1、973重大研究計劃: 豬誘導多能干細胞(iPS)及其分化發(fā)育研究。

    2、轉基因重大專項: 利用生殖系多能性干細胞構建高效的培育優(yōu)良品種豬和轉基因豬的新技術平臺。

    3、中加合作交流項目: 卵子及植入前胚胎細胞體積調控與細胞死亡關系的研究。

    劉林

    4、973重大研究計劃: 卵巢衰老機理及相關重大疾病的基礎研究。

    發(fā)表論文

    代表論文

    1.Agarwal S, Loh YH, McLoughlin EM, Huang J, Park IH, Miller JD, Huo H, Okuka M, Dos Reis RM, Loewer S, Ng HH, Keefe DL, Goldman FD, Klingelhutz AJ, Liu L, Daley GQ. Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature 464:292-296(2010).

    2.Huang J, Okuka M, Wang F, Zuo B, Liang P, Kalmbach K, Liu L, Keefe DL. Generation of pluripotent stem cells from eggs of aging mice. Aging Cell Online (2009).

    3. C, Chen Z, Liu Z, Huang J, Zhang W, Zhou L, Keefe DL, Liu L. Correlation of expression and methylation of imprinted genes with pluripotency of parthenogenetic embryonic stem cells. Human Molecular Genetics 18:2177-2187 (2009).

    4.Liu N, Lu M, Feng XM, Ma FX, Fang ZH, Tian XM, Ren Q, Zhang L, Liu B, Huang PP, Liu L, Han ZC. Exogenous Nanog alleviates but is insufficient to reverse embryonic stem cells differentiation induced by PI3K signaling inhibition. Journal of Cellular Biochemistry 106:1041-1047 (2009).

    5.Chen Z, Liu Z, Huang J, Amano T, Li C, Cao S, Wu C, Liu B, Zhou L, Carter MG, Keefe DL, Yang X, Liu L. Birth of Parthenote mice directly from parthenogenetic embryonic stem cells. Stem Cells 27:2136-2145 (2009).

    6.Keefe DL, Liu L. Telomeres and reproductive aging. Reproduction, Fertility and Development 21:10-14 (2009).

    7.Cao S, Wang F, Chen Z, Liu Z, Mei C, Wu H, Huang J, Li C, Zhou L, Liu L. Isolation and culture of primary bovine embryonic stem cell colonies by a novel method. Journal of Experimental Zoology Part A Ecol Genet Physiol. 311A:368-376 (2009).

    8.Chen L, Liu L. Current progress and prospects of induced pluripotent stem cells. Sci China C Life Sci. 52:622-636 (2009).

    9.Huang J, Deng K, Wu H, Liu Z, Chen Z, Cao S, Zhou L, Ye X, Keefe DL, Liu L. Efficient production of mice from embryonic stem cells injected into four- or eight-cell embryos by piezo micromanipulation. Stem Cells 26:1883-1890 (2008)

    10.Liu L, S. M. Bailey, M. Okuka, P. Mu?oz, C. Li, L. Zhou, C. Wu, E. Czerwiec, L. Sandler, A. Seyfang, M. A. Blasco and Keefe. D. L. Telomere lengthening early in development. Nature Cell Biology 9: 1436-1441 (2007)

    11.Liu Y, Wu C, Lyu Q, Yang D, Albertini DF, Keefe DL, Liu L. Germline stem cells and neo-oogenesis in the adult human ovary. Developmental Biology 306:112-120 (2007)

    12.Liu L and Keefe DL. Chapter 15 Nuclear Transfer Methods to Study Aging in Methods in Molecular Biology: Biological Aging: Methods and Protocols. Humana Press Inc., Totowa, NJ. Pp191-207 (2007)

    13.Keefe DL, Liu L, Marquard K. Telomeres and aging-related meiotic dysfunction in women. Cellular and Molecular Life Sciences 64:139-143 (2007)

    14.Wang X, Liu L, Montagna C, Ried T, Deng CX. Haploinsufficiency of Parp1 accelerates Brca1-associated centrosome amplification, telomere shortening, genetic instability, apoptosis, and embryonic lethality. Cell Death & Differentiation 14:924-931 (2007)

    15.Dai, Y., L. Wang, H. Wang, Y. Liu, Q. Lyu, N. Li, D.L. Keefe, D.F. Albertini and L. Liu. Abnormalities in centrosome remodeling following somatic cell nuclear transfer (SCNT) in bovine oocytes. Reproduction 131:1051-1061 (2006).

    16.Liu, L., Franco, S., Spyropoulos, B., Moens, P.B., Blasco, M.A., and Keefe, D.L. Irregular telomeres impair meiotic synapsis and recombination in mice. Proc Natl Acad Sci U S A 101: 6496-6501 (2004)

    17.Liu, L., C.M. DiGirolamo, P.A.A.S. Navarro, M.A. Blasco and D. L. Keefe. Telomerase deficiency impairs differentiation of mesenchymal stem cells. Experimental Cell Research 294: 1-8 (2004)

    18.Liu, L., J.R. Trimarchi, P. Navarro, M.A. Blasco and D.L. Keefe. Oxidative stress contributes to arsenic-induced telomere attrition, chromosome instability, and apoptosis. The Journal of Biological Chemistry 278:31998u201332004 (2003)

    19.Liu, L., M.A. Blasco, J.R. Trimarchi and D.L. Keefe. An essential role for functional telomeres in mouse germ cells during fertilization and early development. Developmental Biology 249:74-84 (2002)

    20.Liu, L., M.A. Blasco and D.L. Keefe. Requirement of functional telomeres for metaphase chromosome alignments and integrity of meiotic spindles. EMBO Reports

    21.Liu, L., M. Deng, X.C. Tian, and X. Yang. Chapter 17: Activation of mammalian oocytes: Principles and Practice. In: Introduction to Mammalian Reproduction. Editor: Daulat R.P. Tulsiani, Kluwer academic Publishers, MA, USA. pp-

    22.Liu, L., J.R. Trimarchi, P. Smith and D.L. Keefe. Mitochondrial dysfunction leads to telomere attrition and genomic instability. Aging Cell

    23.u, L., James R. Trimarchi, Peter Smith and David L. Keefe. Haploidy but not parthenogenetic activation leads to increased incidence of apoptosis in mouse embryos. Biology of Reproduction

    24.Trimarchi, J. R., Liu, L., Smith, P.J., and Keefe, D.L. Apoptosis recruits two-pore domain potassium channels used for homeostatic volume regulation. American Journal of Physiology

    25.Liu, L., Katherine Hammar, Peter J.S. Smith, Shinya Inoue, David L. Keefe. Mitochondrial modulation of calcium signaling at the initiation of development. Cell Calcium

    26.Dinnyés, A., Dai, Y., Barber, M., Liu, L., Xu, J., Zhou, P., and Yang, X. Development of cloned embryos from adult rabbit fibroblasts: effect of activation treatment and donor cell preparation. Biology of Reproduction

    27.Liu, L. Cloning efficiency and differentiation. Nature Biotechnology 19:406 (2001) (Correspondence).

    28.Liu, L., Oldenbourg, R., Trimarchi, J.R., and Keefe, D.L. A reliable, noninvasive technique for spindle imaging and enucleation of mammalian oocytes. Nature Biotechnology

    主要論文

    陳凌懿,劉林. Current progress and prospects of induced pluripotent stem cells. Science in China

    陳凌懿,劉林. 誘導性多潛能干細胞(iPS)的研究現(xiàn)狀和展望. 中國科學C輯

    Li C, Chen Z, Liu Z, Huang J, Zhang W, Zhou L, Keefe DL, Liu L. Correlation of expression and methylation of imprinted genes with pluripotency of parthenogenetic embryonic stem cells. Human Molecular Genetics

    Cao S, Wang F, Chen Z, Liu Z, Mei C, Wu H, Huang J, Li C, Zhou L, Liu L. Isolation and culture of primary bovine embryonic stem cell colonies by a novel method.. Journal of Experimental Zoology Part A Ecol Genet Physiol

    Chen Z, Liu Z, Huang J, Amano T, Li C, Cao S, Wu C, Liu B, Zhou L, Carter MG, Keefe DL, Yang X, Liu L*. Birth of Parthenote Mice Directly from Parthenogenetic Embryonic Stem Cells. Stem Cells

    Keefe DL, Liu L.. Telomeres and reproductive aging. Reproduction, Fertility and Development

    1. Agarwal S, Loh YH, McLoughlin EM, Huang J, Park IH, Miller JD, Huo H, Okuka M, Dos Reis RM, Loewer S, Ng HH, Keefe DL, Goldman FD, Klingelhutz AJ, Liu L, Daley GQ. . Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature

    Huang J, Okuka M, Wang F, Zuo B, Liang P, Kalmbach K, Liu L*, Keefe DL. Generation of pluripotent stem cells from eggs of aging mice.. Aging Cell -

    Huang J, Okuka M, McLean M, Keefe DL, Liu L*. . Telomere susceptibility to cigarette smoke-induced oxidative damage and chromosomal instability of mouse embryos in vitro . Free Radical Biology & Medicine

    Richards T, Wang F, Liu L, Baltz JM. . Rescue of postcompaction-stage mouse embryo development from hypertonicity by amino acid transporter substrates that may function as organic osmolytes.. Biology of Reproduction

    Liu N, Enkemann SA, Liang P, Hersmus R, Zanazzi C, Huang J, Wu C, Chen Z, Looijenga LH, Keefe DL, Liu L.. Genome-wide gene expression profiling reveals aberrant MAPK and Wnt signaling pathways associated with early parthenogenesis.. J Mol Cell Biol

    Liu N, Lu M, Feng XM, Ma FX, Fang ZH, Tian XM, Ren Q, Zhang L, Liu B, Huang PP, Liu L, Han ZC.. Exogenous Nanog alleviates but is insufficient to reverse embryonic stem cells differentiation induc. J Cell Biochem

    Liu, Z., Hu, Z., Pan, X., Li, M., Togun, T.A., Tuck, D., Pelizzola, M., Huang, J., Ye, X., Yin, Y., Liu, M., Li, C., Chen, Z., Wang, F., Zhou, L., Chen, L., Keefe, D.L., and Liu, L. . Germline competency of parthenogenetic embryonic stem cells from immature oocytes of adult mouse ova. Hum Mol Genet

    Huang J, Wang F, Okuka M, Liu N, Ji G, Ye X, Zuo B, Li M, Liang P, Ge WW, Tsibris JC, Keefe DL, Liu L.. Association of telomere length with authentic pluripotency of ES/iPS cells.. Cell Res

    Wang F, Yin Y, Ye X, Liu K, Zhu H, Wang L, Chiourea M, Okuka M, Ji G, Dan J, Zuo B, Li M, Zhang Q, Liu N, Chen L, Pan X, Gagos S, Keefe DL, Liu L.. Molecular insights into the heterogeneity of telomere reprogramming in induced pluripotent stem cells. Cell Res.

    榮譽記錄

    科研工作先后獲得國家教育部博士點基金,國家自然科學基金,英國海外發(fā)展中英技術合作基金,美國農(nóng)業(yè)部,美國衛(wèi)生部,康乃爾大學及康州大學博士后基金,布朗大學婦女兒童醫(yī)院教師研究基金,國家杰出青年基金、中國衛(wèi)生部部屬(管)醫(yī)療機構臨床學科重點、廣州市科技計劃項目、中國-加拿大國際合作項目、國家重大科學研究計劃(973)項目首席科學家、國家重大轉基因專項等科研基金的資助。

    重要成果

    生殖衰老治療研究獲突破

    2020-01-05 10:12:17 來源:健康報

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