• 但佳猛 (Jiameng Dan)

    博士,教授

    PhD, Professor

    E-mail:danjm@lpbr.cn

    一、教育及工作经历 (Education and Work Experience)

    2021年5月-至今,昆明理工大学灵长类转化医学研究院,教授

    2017年12月-2021年4月,美国加州索克研究所 (Salk Institute),助理研究员

    2014年11月-2017年12月,美国德州大学MD安德森癌症中心 (MD Anderson Cancer Center),博士后

    2007年9月-2014年6月,南开大学生命科学学院,细胞生物学专业,干细胞与发育生物学研究方向获理学博士学位(硕博连读)

    2003年9月-2007年6月,三峡大学,生物科学学士学位

     

    05/2021-Present: Professor, State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China

    12/2017-04/2021: Research Associate, Salk Institute, La Jolla, USA

    11/2014-12/2017: Postdoctoral Fellow, The University of Texas MD Anderson Cancer Center, Houston, USA

    09/2007-06/2014: School of Life Sciences, Nankai University, Tianjin, China, Ph.D. in Cell Biology

    09/2003-06/2007: China Three Gorges University, Hubei, China, B.S. in Biological Science

    二、主要研究方向与领域描述 (Research Interests and Description)

    胚胎干细胞多能性与全能性的维持与转换调控机制

    哺乳动物早期胚胎材料有限,特别是灵长类胚胎更加不易获得,进而严重制约着对早期胚胎发育的研究。全能性在小鼠里面局限于受精卵和2细胞期胚胎,在人里面局限于受精卵和4-8胚胎期之前的卵裂球,具备同时向胎儿和胎盘组织分化的潜能。合子基因组激活(Zygotic genome activation, ZGA)在小鼠里面发生在2细胞胚胎期,在人里面发生在8细胞胚胎期。最近在小鼠和人的胚胎干细胞(naïve embryonic stem cells, naïve ESCs)群体中分别发现占比1%左右的二细胞胚胎样干细胞(2C-like cells, 2CLCs)和八细胞胚胎样干细胞(8C-like cells, 8CLCs)。2CLCs与8CLCs和ZGA发生时期早期胚胎共享诸多分子及表观遗传特征,2CLCs更进一步证实具有全能性,已成为研究早期胚胎发育的良好体外模型。我们将进一步在猴naïve ESCs中鉴定可能的类似细胞群体及相关的分子表观特征,并利用此三种体外细胞模型探讨胚胎干细胞多能性与全能性维持及相互转换的机制、哺乳动物(包括人和猴)早期胚胎全能性获得、合子基因组激活、全能性向多能性转变、表观遗传维持与重建调控机制等重要科学问题。

     

    早期胚胎发育表观遗传调控机制

    早期胚胎发育从受精卵到囊胚期经历了剧烈的表观遗传重构过程,包括全基因组DNA的去甲基化,从而确保胚胎发育的正常进行。我们将深入探讨早期胚胎发育过程中全基因组DNA去甲基化的调控及维持机制,并探讨相关调控及维持机制在灵长类动物早期胚胎发育进程中的保守性,为生殖健康提供线索与科学依据。

     

    基因编辑技术

    基因编辑技术特别是CRISPR/Cas9技术在细胞核基因组上已得到了广泛的应用,发展出多种基因编辑技术,如base editing、prime editing等,并深刻的改变了生命科学的各个方面。目前CRISPR/Cas9基因编辑技术还无法有效的应用于线粒体基因组DNA突变引发的多种疾病。我们致力于开发作用于线粒体基因组的基因编辑技术,并应用于灵长类生殖健康相关的疾病。

     

    Regulation and maintenance of pluripotency and totipotency

    The scarcity of mammalian early embryos, especially embryos from primates, greatly restricts our understanding of early embryogenesis. Only zygotes and 2C embryos in mice, zygotes and embryos before 4-8 stage in human, are recognized to be totipotent. Zygotic genome activation (ZGA) occurs at 2C stage in mice and 8C stage in human, respectively. Recently, it has been shown that a small population (1%) called 2C-like cells (2CLCs) in mouse naïve ESC and 8C-like cells (8CLCs) in human naïve ESCs culture share many molecular and epigenetic features with 2C embryos in mice and 8C embryos in human, respectively. Importantly, 2CLCs are demonstrated to be totipotent, which can give rise to both embryonic and extraembryonic tissues. Thus, both 2CLCs and 8CLCs are great in vitro models for investigating embryogenesis. We would like to further identify the similar totipotent population in monkey naïve ESCs and related molecular and epigenetic features. We will apply these three different in vitro cell models to investigate the mechanisms underlying the maintenance and transition between pluripotency and totipotency, early embryo totipotency acquisition, ZGA, epigenetic maintenance and reprogramming.

     

    Epigenetic regulation in early embryogenesis

    It is well known that the preimplantation embryo development processes are accompanied with dramatic epigenetic reprogramming, including global DNA demethylation, which ensure proper embryogenesis. We aim to decipher the mechanisms regulating and maintaining the global DNA demethylation in early embryo development, and investigate whether the mechanisms are conserved in primates. The study will provide clues and potential strategies to improve reproductive health in mammals, especially in primates.

     

    Genome editing technologies

    The newly developed genome editing technologies, especially CRISPR/Cas9 technologies including base editing and prime editing, have been wildly applied in every aspect of life sciences in nuclear genome, and have greatly advanced our understanding of life sciences. However, it is still not possible to precisely manipulate mitochondrial DNA mutations that cause many mitochondrial diseases. We aim to develop mitoCRISPR technologies to model mitochondrial diseases in animals including non-human primates, and to investigate the pathogenesis of mitochondrial diseases related to reproductive health.

    三、承担与参与科研项目情况

    2016年5月-2017年5月,美国德州大学MD安德森癌症中心校内短期项目,主持

    2016年9月-2017年11月,美国国立卫生研究院R01项目,主要参与人

    2014年11月-2017年11月,美国国立卫生研究院R01项目,主要参与人

    2009年9月-2014年6月,科技部973重大专项科研项目,主要参与人

    四、代表性论文 (Publications) (#, Co-first author; *, Corresponding author)

    1. Dan J* and Chen T*. Genetic Studies on Mammalian DNA Methyltransferases (2nd Edition). Adv Exp Med Biol., 2022 ( In Press)
    2. Dan J*, Zhou Z, Wang F, Wang H, Guo R, Keefe DL, Liu L*. Zscan4 Contributes to Telomere Maintenance in Telomerase-Deficient Late Generation Mouse ESCs and Human ALT Cancer Cells. Cells, 2022 Jan 28; 11(3):456.
    3. Dan J#, Memczak S#, Belmonte JCI*. Expanding the Toolbox and Targets for Gene Editing. Trends in Molecular Medicine, 2021 Mar; 27(3):203-206.
    4. Dan J, Rousseau P, Hardikar S, Veland N, Wong J, Autexier C, Chen T*. Zscan4 Inhibits Maintenance DNA Methylation to Regulate Telomere Elongation in Mouse Embryonic Stem Cells. Cell Reports, 2017, 20(8):1936-1949.
    5. Dan J#, Liu Y#, Liu N#, Chiourea M, Okuka M, Wu T, Ye X, Mou C, Wang L, Wang L, Yin Y, Yuan J, Zuo B, Wang F, Li Z, Pan X, Yin Z, Chen L, Keefe DL, Gagos S, Xiao A*, Liu L*. Rif1 maintains telomere length homeostasis of ESCs by mediating heterochromatin silencing. Developmental Cell, 2014, 29 (1): 7-19. 
    6. Dan J and Chen T*. Genetic Studies on Mammalian DNA Methyltransferases. Adv Exp Med Biol., 2016; 945:123-150.
    7. Dan J, Yang J, Liu Y, Xiao A, Liu L*. Roles for Histone Acetylation in Regulation of Telomere Elongation and Two-Cell State in Mouse ES Cells. Journal of Cellular Physiology, 2015, 230(10): 2337-44.
    8. Dan J, Li M, Yang J, Li J, Okuka M, Ye X, Liu L*. Roles for Tbx3 in regulation of two-cell state and telomere elongation in mouse ES cells. Scientific Reports, 2013, 3:3492. 
    9. Liu H#, Li R#, Liao H#, Min Z, Wang C, Yu Y, Shi L, Dan J, Nunez E,  Martinez L, Wu J, Belmonte JCI*. Novel chemical combinations potentiate human pluripotent stem cell-derived 3D pancreatic progenitor clusters toward functional β cells. Nature Communications, 2021 Jun 7; 12(1):3330.
    10. Veland N, Zhong Y, Gayatri S, Dan J, Strahl B, Rothbart S, Bedford M, Chen T*. The Arginine Methyltransferase PRMT6 Regulates DNA Methylation and Contributes to Global DNA Hypomethylation in Cancer. Cell Reports, 2017, 21(12):3390-3397.
    11. Kim J, Zhao H, Dan J, Kim S, Hardikar S, Hollowell D, Lin K, Lu Y, Takata Y, Shen J, Chen T*. Maternal Setdb1 is required for meiotic progression and preimplantation development in mouse. PLoS Genetics, 2016, 12(4): e1005970.
    12. Yang J, Guo R, Wang H, Zhou Z, Ye X, Dan J, Wang H, Gong T, Deng W, Yin Y, Mao S, Wang L, Ding J, Li J, Dawlaty M, Wang J, Xu G, Liu L*. Tet Enzymes Regulates Telomere Maintenance and Chromosomal Stability of Mouse ESCs. Cell Reports, 2016 May 24, 15 (8): 1809-21.
    13. Zhang Q, Dan J, Wang H, Guo R, Mao J, Fu H, Wei X, Liu L*. Tcstv1 and Tcstv3 elongate telomeres of mouse ES cells. Scientific Reports, 2016, 6:19852.
    14. Wang L, Ye X, Zhao Q, Zhou Z, Dan J, Zhu Y, Chen Q, Liu L*. Drp1 is dispensable for mitochondria biogenesis in induction to pluripotency but required for differentiation of ES cells. Stem Cell and Development, 2014, 23(20): 2422-34.
    15. Hao J, Li W, Dan J, Ye X, Wang F, Zeng X, Wang L, Wang H, Cheng Y, Liu L*, Shui W*. Reprogramming- and pluripotency-associated membrane proteins in mouse stem cells revealed by label-free quantitative proteomics. Journal of Proteomics, 2013, 86:70-84.
    16. Zuo B#, Yang J#, Wang F, Wang L, Yin Y, Dan J, Liu N, Liu L*. Influences of lamin A levels on induction of pluripotent stem cells. Open Biology, 2012, 1(11): 1118-27.
    17. 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 Research, 2012, 22 (4): 757-68.

    五、实验室成员

    硕士研究生:2021级:常晓毅,杜则玲

    六、招生招聘

    1. 欢迎优秀的本科生和硕士报考本实验室的硕士及博士研究生。
    2. 实验室招聘科研助理
    • 具有生物学/医学相关背景及学士以上学历;
    • 掌握基本的分子生物学技术和细胞培养技术,有胚胎显微操作经验者优先; 
    • 工作认真负责,交流沟通能力良好。
    1. 实验室招聘博士后(若干名)或助理研究员
    • 具有分子、细胞、或发育生物学等相关学科背景,并(将)取得博士学位;有基因编辑、胚胎干细胞及早期胚胎发育研究经验者优先;
    • 以第一作者发表过SCI论文1篇以上,能独立开展科研工作,并协助指导研究生;
    • 具有较好的思辨能力及较强的自我激励动力,较好的交流能力和团队合作精神;
    • 具备较好的英文听、说、读、写能力。

     

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