但佳猛 (Jiameng Dan)

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)

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

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

11/2014-12/2017: Postdoctoral Fellow, TheUniversity of Texas MD Anderson Cancer Center, Houston, USA
09/2007-06/2014: School of Life Sciences, NankaiUniversity, Tianjin, China, Ph.D. in Cell Biology

1. 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。

2. 早期胚胎发育表观遗传调控机制

哺乳动物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去甲基化的生物学意义及调控机制，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，为人类生殖健康提供科学依据及临床解决方案。

1. 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.

2. 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 ensures proper embryogenesis. We aim to decipher the biological significance and mechanisms regulating global DNA demethylation processes in early embryo development, and investigate whether the mechanisms are conserved in primates. The study will provide scientific clues and potential strategies to improve reproductive health in mammals, especially in primates. 

1. 国家自然科学基金面上项目，二细胞胚胎样干细胞获得发育全能性的机制研究，32270845, 2023-01至2026-12，54万元，主持。

2. 云南省“兴滇英才支持计划”青年人才项目支持计划，哺乳动物早期发育胚胎中介导DNMT1细胞质定位 的截留因子鉴定及其作用机制研究，2022-12至2027-12，KKRD202273103，90万元，主持。

3. 云南省科技厅/昆明理工大学“双一流”创建联合专项重点项目，哺乳动物原始生殖细胞发育过程中DNA去甲基化重编程的生物学意义研究，2022-10至2025-09，202201BE070001-006，100万元，主持。

4. 云南省基础研究专项面上项目，哺乳动物早期胚胎发育DNA去甲基化重编程的生物学意义研究，2023-06至2026-05，10万元，主持。

5. 昆明理工大学灵长类转化医学研究院高层次人才启动经费，主持。

6. 美国德州大学MD安德森癌症中心校内短期项目，2016-05至2017-05，6万美元（约40万元人民币），主持。

1. Dan J*, Du Z, Zhang J, ChenT*. The interplay between H3K36 methylation and DNA methylation in cancer.Cancer Biol Med. 2023, 20(8):545-52.
2. Dan J* and Chen T*. Writers,erasers, and readers of DNA and histone methylation marks(Book chapter). Epigenetic Cancer Therapy(2^nd Edition), ,2023;39-63
3. Dan J* and Chen T*. Genetic Studies on Mammalian DNA Methyltransferases (2^ndEdition).Adv Exp Med Biol., 2022; 1389:111-136.
4. Dan J*, Zhou Z, Wang F, Wang H, Guo R, Keefe DL, Liu L*. Zscan4 Contributes toTelomere Maintenance in Telomerase-Deficient Late Generation Mouse ESCs and Human
   ALT Cancer Cells. Cells, 2022Jan 28; 11(3):456.
5. Dan J^#, Memczak S^#, Belmonte JCI*. Expanding the Toolbox and Targets for Gene Editing. Trends in Molecular Medicine, 2021 Mar; 27(3):203-206.
6. 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.
7. 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 ofESCs by mediating heterochromatin silencing. Developmental Cell, 2014, 29 (1): 7-19.
8. Dan Jand Chen T*. Genetic Studies on Mammalian DNA Methyltransferases. Adv Exp Med Biol., 2016;945:123-150.
9. 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.
10. Dan J, Li M, Yang J, Li J, Okuka M, Ye X, Liu L*. Rolesfor Tbx3 inregulation of two-cell state and telomere elongation in mouse ES cells. ScientificReports, 2013, 3:3492.
11. Liu H^#, Li R^#, Liao H^#,Min Z, Wang C, Yu Y, Shi L, Dan J,Nunez E, Martinez L, WuJ, Belmonte JCI*. Novel chemical combinations potentiate human pluripotent stem
    cell-derived 3D pancreatic progenitor clusters toward functional β cells. NatureCommunications, 2021 Jun 7; 12(1):3330.
12. Veland N, Zhong Y, Gayatri S, Dan J, Strahl B, Rothbart S, Bedford M,Chen T*. The Arginine MethyltransferasePRMT6 Regulates DNA Methylation and Contributes to Global DNA Hypomethylation in Cancer. CellReports, 2017, 21(12):3390-3397.
13. Kim J, Zhao H, Dan J, Kim S, Hardikar S, Hollowell D, LinK, 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.
14. 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.
15. Zhang Q, Dan J, Wang H, Guo R, Mao J, Fu H, Wei X,Liu L*. Tcstv1 andTcstv3 elongate telomeres of mouse ES cells. Scientific Reports, 2016, 6:19852.
16. Wang L, Ye X, Zhao Q, Zhou Z, Dan J, Zhu Y, Chen Q, Liu L*. Drp1 is dispensable for mitochondria biogenesisin induction to pluripotency but required for differentiation of ES cells. StemCell and Development, 2014,23(20): 2422-34.
17. Hao J, Li W, DanJ, 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 ofProteomics, 2013, 86:70-84.
18. Zuo B^#, Yang J^#, Wang F, Wang L, Yin Y, Dan J, Liu N, Liu L*. Influences oflamin A levels on induction of pluripotent stem cells. Open Biology,2012, 1(11): 1118-27.
19. 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 oftelomere reprogramming in induced pluripotent stem cells. Cell Research,2012, 22 (4): 757-68.

1. 欢迎优秀的本科生和硕士生报考本实验室的硕士和博士研究生。

2. 实验室招聘博士后、助理研究员或讲师

要求具有分子、细胞、或发育生物学等相关学科背景，并（将）取得博士学位；有胚胎干细胞、早期胚胎发育研究或生物信息学分析经验者优先； 2）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；3）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；4）具备较好的英文听、说、读、写能力。  

有意者请将简历和支撑材料发送至danjm@lpbr.cn