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基础医学系

纪家葵

履历

    教育经历:

    1997/09-2003/09,美国康奈尔大学医学院/史隆凯特林癌症研究中心分子、细胞生物与遗传学系,博士

    1992/09-1997/08, 美国爱荷华州立大学,生物化学专业,学士和硕士

    工作经历:

    2010/05-至今, 清华大学,医学院,研究员、博士生导师

    2007/09-2010/04, 美国斯坦福大学,副研究员

    2004/05-2007/08, 美国加州大学旧金山分校,博士后研究

    2003/5-2004/05, 美国康奈尔大学,医学院/史隆凯特林癌症研究中心分子、细胞生物与遗传学系,博士后研究


研究领域与方向

生殖细胞传递生物的全能性及创造生物的多样性。精卵结合后,新生命跟据遗传图谱及表观遗传信息,逐渐发育生长。本实验室致力于研究生殖发育过程的分子机制,尤其是人类生殖细胞的形成、减数分裂的启动、生殖细胞对早期胚胎发育的影响,包括导致不孕不育症的遗传及分子机理研究。受限于取样的困难,我们对人类配子的形成与成熟过程的了解,多借助于模式生物,而模式生物与人类配子形成的机制有许多不同。因此,我们利用人类胚胎干细胞来构建生殖细胞体外分化发育的模型,这提供我们崭新的体外平台来研究人类生殖发育特有的机制。此外,我们也利用干细胞分化及细胞重编程技术,获取具有免疫豁免功能的细胞,用于解决细胞移植的免疫排斥及治疗自身免疫性疫病。


学术荣誉与奖励

    2010, 2011,2017

    拜耳研究员奖

    2014

    强生研究员奖

    2014

    清华大学良师益友


关键词

干细胞、生殖发育、遗传疾病

代表性论文

1)       Li L, Yang R, Yin C, Kee K*. Studying human reproductive biology through single-cell analysis and in vitro differentiation of stem cells into germ cell-like cells. Hum Reprod Update. 2020. doi:10.1093/humupd/dmaa021.

2)       Ye M, Yang ZY, Zhang Y, Xing YX, Xie QG, Zhou JH, Wang L, Xie W, Kee K*, Chian RC*. Single-cell multiomic analysis of in vivo and in vitro matured human oocytes. Hum Reprod. 2020 Apr 28;35(4):886-900. doi: 10.1093/humrep/deaa044.

3)        Gao H, Zheng C, Du J, Wu Y, Sun Y, Han C*, Kee K*, Rao Y*. FAK-targeting PROTAC as a Chemical Tool for the Investigation of Non-Enzymatic FAK Function in Mice. Protein Cell. 2020 May 25. doi: 10.1007/s13238-020-00732-8.

4)       Liang J, Wang N, He J, Du J, Guo Y, Li L, Wu W, Yao C, Li Z, Kee K*. Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4. Elife. 2019 Nov 11;8. pii: e48767. doi: 10.7554/eLife.48767.

5)       Wang B, Li L, Zhu Y, Zhang W, Wang X, Chen B, Li T, Pan H, Wang J, Kee K*, Cao Y*. Sequence variants of KHDRBS1 as high penetrance susceptibility risks for primary ovarian insufficiency by mis-regulating mRNA alternative splicing. Hum Reprod. 2017 Oct 1;32(10):2138-2146. doi: 10.1093/humrep/dex263.

6)       Jung D, Xiong J, Ye M, Qin X, Li L, Cheng S, Luo M, Peng J, Dong J, Tang F, Shen W, Matzuk MM, Kee K*.In vitro differentiation of human embryonic stem cells into ovarian follicle-like cells. Nat Commun.2017 Jun 12;8:15680. doi: 10.1038/ncomms15680.

7)       Zhu C, Gao Y, Guo H, Xia B, Song J, Wu X, Zeng H, Kee K, Tang F, Yi C*.Single-Cell 5-Formylcytosine Landscapes of Mammalian Early Embryos and ESCs at Single-Base Resolution. Cell Stem Cell. 2017 May 4;20(5):720-731.e5.

8)       Li L, Sha Y, Wang X, Li P, Wang J, Kee K, Wang B* (2017). Whole-exome sequencing identified a homozygous BRDT mutation in a patient with acephalic spermatozoa. Oncotarget 8(12): 19914-19922.

9)       Guo J, Ma D, Huang R, Ming J, Ye M, Kee K, Xie Z, Na J*. (2017). An inducible CRISPR-ON system for controllable gene activation in human pluripotent stem cells. Protein Cell. 8(5):379-393. doi: 10.1007/s13238-016-0360-8.

10)     Li L, Wang B, Zhang W, Chen B, Luo M, Wang J, Wang X, Cao Y*, Kee K*. (2017). A homozygous NOBOX truncating variant causes defective transcriptional activation and leads to primary ovarian insufficiency. Hum Reprod 32(1): 248-255. doi: 10.1093/humrep/dew271.

11)     He Z, Kee K*. (2017). Generating a Genome Editing Nuclease for Targeted Mutagenesis in Human Cells. Methods Mol Biol 1498: 153-162. doi:10.1007/978-1-4939-6472-7_10.

12)    Zhang B, Zheng H, Huang B, Li W, Xiang Y, Peng X, Ming J, Wu X, Zhang Y, Xu Q, Liu W, Kou X, Zhao Y, He W, Li C, Chen B, Li Y, Wang Q, Ma J, Yin Q, Kee K, Meng A, Gao S, Xu F, Na J*, Xie W*. (2016). Allelic reprogramming of the histone modification H3K4me3 in early mammalian development. Nature 537(7621): 553-557. doi: 10.1038/nature19361.

13)    Li L, Zhou X, Wang X, Wang J, Zhang W, Wang B, Cao Y*, Kee K*. (2016). A dominant negative mutation at the ATP binding domain of AMHR2 is associated with a defective anti-Mullerian hormone signaling pathway. Mol Hum Reprod 22(9): 669-678. doi:10.1093/molehr/gaw040.

14)   Jung D, Kee K*. (2015). Insights into female germ cell biology: from in vivo development to in vitro derivations. Asian J Androl 17(3): 415-420. doi:10.4103/1008-682X.148077.

15)    Liu C, Lin J, Li L, Zhang Y, Chen W, Cao Z, Zuo H, Chen C*, Kee K*. (2015). HPV16 early gene E5 specifically reduces miRNA-196a in cervical cancer cells. Sci Rep 5: 7653. doi: 10.1038/srep07653.

16)    Lin J, Chen H, Luo L, Lai Y, Xie W, Kee K*. (2015). Creating a monomeric endonuclease TALE-I-SceI with high specificity and low genotoxicity in human cells. Nucleic Acids Res 43(2): 1112-1122. doi: 10.1093/nar/gku1339.

17)    Chung J, Dash R, Kee K, Barral JK, Kosuge H, Robbins RC, Nishimura D, Reijo- Pera RA, Yang PC*. (2012). Theranostic effect of serial manganese-enhanced magnetic resonance imaging of human embryonic stem cell derived teratoma. Magn Reson Med 68(2): 595-599. doi: 10.1002/mrm.23262.

18)    Nguyen HN, Byers B, Cord B, Shcheglovitov A, Byrne J, Gujar P, Kee K, Schüle B, Dolmetsch RE, Langston W, Palmer TD*, Pera RR*. (2011). LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell 8(3): 267-280. doi: 10.1016/j.stem.2011.01.013.

19)   Panula S, Medrano JV, Kee K, Bergström R, Nguyen HN, Byers B, Wilson KD, Wu JC, Simon C, Hovatta O, Reijo Pera RA*. (2011). Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells. Hum Mol Genet 20(4): 752-762. doi: 10.1093/hmg/ddq520.

20)    Kee K*, Flores M, Cedars MI, Reijo Pera RA*. (2010). Human primordial germ cell formation is diminished by exposure to environmental toxicants acting through the AHR signaling pathway. Toxicol Sci 117(1): 218-224. doi: 10.1093/toxsci/kfq179.

21)    Kee K, Pera RA, Turek PJ*. (2010). Testicular germline stem cells. Nat Rev Urol 7(2): 94-100. doi: 10.1038/nrurol.2009.263.

22)    Kee K, Angeles VT, Flores M, Nguyen HN, Reijo Pera RA*. (2009). Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation. Nature 462(7270): 222-225. doi: 10.1038/nature08562.

23)    McElroy SL, Kee K, Tran N, Menses J, Giudice LC, Reijo Pera RA*. (2008). Developmental competence of immature and failed/abnormally fertilized human oocytes in nuclear transfer. Reprod Biomed Online 16(5): 684-693. doi:10.1016/s1472-6483(10)60483-x.

24)   Kee K, Reijo Pera RA*. (2008). Human germ cell lineage differentiation from embryonic stem cells. CSH Protoc 2008: pdb prot5048. doi: 10.1101/pdb.prot5048.

25)    International Stem Cell Initiative (2007). Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat Biotechnol 25(7): 803-816. doi:10.1038/nbt1318.

26)    Kee K, Gonsalves JM, Clark AT, Pera RA*. (2006). Bone morphogenetic proteins induce germ cell differentiation from human embryonic stem cells. Stem Cells Dev 15(6): 831-837. doi: 10.1089/scd.2006.15.831.

27)    Henderson KA, Kee K, Maleki S, Santini PA, Keeney S*. (2006). Cyclin-dependent kinase directly regulates initiation of meiotic recombination. Cell 125(7): 1321-1332. doi: 10.1016/j.cell.2006.04.039.

28)    Kee K, Protacio RU, Arora C, Keeney S*. (2004). Spatial organization and dynamics of the association of Rec102 and Rec104 with meiotic chromosomes. EMBO J 23(8): 1815-1824. doi: 10.1038/sj.emboj.7600184.

29)    Arora C, Kee K, Maleki S, Keeney S*. (2004). Antiviral protein Ski8 is a direct partner of Spo11 in meiotic DNA break formation, independent of its cytoplasmic role in RNA metabolism. Mol Cell 13(4): 549-559. doi: 10.1016/s1097-2765(04)00063-2.

30)   Kee K, Keeney S*. (2002). Functional interactions between SPO11 and REC102 during initiation of meiotic recombination in Saccharomyces cerevisiae. Genetics 160(1): 111-122.

31)   Kee K, Niu L, Henderson E*. (1998). A Tetrahymena thermophila G4-DNA binding protein with dihydrolipoamide dehydrogenase activity. Biochemistry 37(12): 4224-4234. doi: 10.1021/bi9716377

 

*:通讯作者


联系方式

Email: kkee at tsinghua.edu.cn

Phone: +86-10-62794200

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