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纪家葵

完美体育·(中国)官方网站长聘教授

清华完美体育·(中国)官方网站(Tsinghua Medicine) 主任助理

清华大学国际合作交流特使

E-mail: kkee@tsinghua.edu.cn

Tel: +86-10-62794200

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教育背景

1997-2003 美国康奈尔大学完美体育·(中国)官方网站/史隆凯特林癌症研究中心分子、细胞生物与遗传学系,博士

1992-1997 美国爱荷华州立大学,生物化学专业,学士和硕士(双荣誉学位)

工作经历

2024-至今 清华大学基础完美体育·(中国)官方网站长聘教授,清华完美体育·(中国)官方网站主任助理 (Assistant Chancellor)

2022-2024 完美体育·(中国)官方网站 长聘教授

2021-2023 完美体育·(中国)官方网站基础医学系副系主任

2016-2022 完美体育·(中国)官方网站 长聘副教授

2010-2016 完美体育·(中国)官方网站 副教授

2007-2010 美国斯坦福大学,副研究员

2004-2007 美国加州大学旧金山分校,博士后研究

2003-2004 美国康奈尔大学,完美体育·(中国)官方网站/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

利用人类胚胎干细胞构建体外平台研究人类生殖发育特有的机制,推进人类在生殖发育机理及不孕不育疾病方面的研究

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,新生命根据遗传图谱及表观遗传调控,逐渐发育生长。 团队致力于研究生殖发育过程的分子机制,尤其是调控人类生殖细胞发育的RNA结合蛋白、减数分裂的启动、及导致不孕不育症的遗传及分子机理。受限于取样的困难,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,团队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,提供崭新的体外平台来研究人类生殖发育特有的机制。此体外平台也提供团队在空间站及航天飞行特殊条件下研究人类生殖细胞的机会。此外,他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。

纪家葵研究团队在国际上首次创立人类胚胎干细胞分化为单倍体生殖细胞体系,并利用基因表达调控技术,定向分化人类胚胎干细胞为卵泡样细胞,创立了一系列人类胚胎干细胞定向分化为生殖细胞的研究体系,同时为生殖健康及相关疾病的研究及预防治疗提供重要理论基础和技术支持,推进了人类在生殖发育机理及不孕不育疾病方面的研究进展。

纪家葵教授的“一种将成纤维细胞体外重编为Sertoli细胞的方法及其应用”专利技术已经许可给一家北京生物医药公司,用于开发‘新型人工免疫豁免微环境及辅助生殖临床治疗平台’。

纪家葵教授长期致力于生殖医学与及再生医学研究,利用人类干细胞体外分化技术,结合分子生物学、细胞生物学及遗传学研究方法,建立人类胚胎干细胞分化为生殖细胞体系,定向分化人类胚胎干细胞为精子细胞、卵泡细胞,重编程纤维细胞为人类睾丸支持细胞。並利用所建立的技术体系,与多家临床单位合作,揭示多个造成不孕不育突变的致病机制,改进辅助生殖技术,並在 Nature, Developmental Cell, Nature Communications, Human Reproduction Update 等期刊发表多篇论文。所建立的体外分化人类生殖细胞体系被选入参与中国国家航天项目天舟1号及空间站研究项目。此外,其团队利用细胞重编程技术获取具有免疫豁免功能的细胞已获发明专利,正与企业及医院共同转化为细胞治疗技术,用于解决细胞或组织移植的免疫排斥难题及治疗自身免疫性疫病。

荣誉奖励

2010/2011/2017 拜耳研究员奖

2014 强生研究员奖

2014 清华大学良师益友奖

代表性论文

1) He J, Yan A, Chen B, Huang J, Kee K*. 3D genome remodeling and homologous pairing during meiotic prophase of mouse oogenesis and spermatogenesis. Dev Cell. 2023 Nov 13: S1534-5807(23)00553-1. doi: 10.1016/j.devcel.2023.10.009.

2) Wang N, He J, Feng X, Liao S, Zhao Y, Tang F, Kee K*. Single-cell profiling of lncRNAs in human germ cells and molecular analysis reveals transcriptional regulation of LNC1845 on LHX8. Elife. 2023 Jan 5;12:e78421. doi: 10.7554/eLife.78421.

3) Yan A, Xiong J, Zhu J, Li X, Xu S, Feng X, Ke X, Wang Z, Chen Y, Wang HW, Zhang MQ*, Kee K*. DAZL regulates proliferation of human primordial germ cells by direct binding to precursor miRNAs and enhances DICER processing activity. Nucleic Acids Res. 2022 Oct 24:gkac856. doi: 10.1093/nar/gkac856.

4) Hu W, Zeng H, Shi Y, Zhou C, Huang J, Jia L, Xu S, Feng X, Zeng Y, Xiong T, Huang W, Sun P, Chang Y, Li T, Fang C, Wu K, Cai L, Ni W, Li Y, Yang Z, Zhang QC, Chian R, Chen Z, Liang X*, Kee K*. Single-cell transcriptome and translatome dual-omics reveals potential mechanisms of human oocyte maturation. Nat Commun. 2022 Aug 30;13(1):5114. doi: 10.1038/s41467-022-32791-2.

5) 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 Sep 1;26(5):670-688. doi:10.1093/humupd/dmaa021.

6) 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.

7) 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.

8) 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.

9) 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.

10) 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.

1) Wen F, Ding Y, Wang M, Du J, Zhang S, Kee K*. FOXL2 and NR5A1 induce human fibroblasts into steroidogenic ovarian granulosa-like cells. Cell Prolif. 2024 Jan 8:e13589.

Link to publication: doi: 10.1111/cpr.13589

Link to Pubmed: PMID: 38192172

2) Ding Y, He Z, Sha Y, Kee K*, Li L*. Eif4enif1 haploinsufficiency disrupts oocyte

mitochondrial dynamics and leads to subfertility. Development. 2023 Dec 1;150(23):dev202151.

Link to publication: doi: 10.1242/dev.202151

Link to Pubmed: PMID: 38088064

3) He J, Yan A, Chen B, Huang J, Kee K*. 3D genome remodeling and homologous pairing during meiotic prophase of mouse oogenesis and spermatogenesis. Dev Cell. 2023 Nov 13: S1534-5807(23)00553-1.

Link to publication: doi: 10.1016/j.devcel.2023.10.009

Link to Pubmed: PMID: 37963468

4) Huang J, Chen P, Jia L, Li T, Yang X, Liang Q, Zeng Y, Liu J, Wu T, Hu W, Kee K*, Zeng H*, Liang X*, Zhou C*. Multi-Omics Analysis Reveals Translational Landscapes and Regulations in Mouse and Human Oocyte Aging. Adv Sci (Weinh). 2023 Sep;10(26):e2301538.

Link to publication: doi: 10.1002/advs.202301538

Link to Pubmed: PMID: 37401155

5) Wang N, He J, Feng X, Liao S, Zhao Y, Tang F, Kee K*. Single-cell profiling of lncRNAs in human germ cells and molecular analysis reveals transcriptional regulation of LNC1845 on LHX8. Elife. 2023 Jan 5;12:e78421.

Link to publication: doi: 10.7554/eLife.78421

Link to Pubmed: PMID: 36602025

6) Yan A, Xiong J, Zhu J, Li X, Xu S, Feng X, Ke X, Wang Z, Chen Y, Wang HW, Zhang MQ*, Kee K*. DAZL regulates proliferation of human primordial germ cells by direct binding to precursor miRNAs and enhances DICER processing activity. Nucleic Acids Res. 2022 Oct 24:gkac856.

Link to publication: doi: 10.1093/nar/gkac856

Link to Pubmed: PMID: 36273819

7) Hu W, Zeng H, Shi Y, Zhou C, Huang J, Jia L, Xu S, Feng X, Zeng Y, Xiong T, Huang W, Sun P, Chang Y, Li T, Fang C, Wu K, Cai L, Ni W, Li Y, Yang Z, Zhang QC, Chian R, Chen Z, Liang X*, Kee K*. Single-cell transcriptome and translatome dual-omics reveals potential mechanisms of human oocyte maturation. Nat Commun. 2022 Aug 30;13(1):5114.

Link to publication: doi: 10.1038/s41467-022-32791-2

Link to Pubmed: PMID: 36042231

8) Wang Y, Xie H, Chang X, Hu W, Li M, Li Y, Liu H, Cheng H, Wang S, Zhou L, Shen D, Dou S, Ma R, Mao Y, Zhu H, Zhang X, Zheng Y, Ye X, Wen L, Kee K*, Cui H*, Tang F*. Single-cell dissection of the multiomic landscape of high-grade serous ovarian cancer. Cancer Res. 2022 Aug 15:CAN-21-3819. Epub ahead of print.

Link to publication: doi: 10.1158/0008-5472.CAN-21-3819

Link to Pubmed: PMID: 35969151

9) Chen B, Zhu G, Yan A, He J, Liu Y, Li L, Yang X, Dong C, Kee K*. IGSF11 is required for pericentric heterochromatin dissociation during meiotic diplotene. PLoS Genet. 2021 Sep 7;17(9):e1009778.

Link to publication: doi: 10.1371/journal.pgen.1009778

Link to Pubmed: PMID: 34491997

10) 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 Sep 1;26(5):670-688.

Link to publication: doi:10.1093/humupd/dmaa021

Link to Pubmed: PMID: 32464645

11) 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.

Link to publication: doi: 10.1093/humrep/deaa044

Link to Pubmed: PMID: 32325493

12) 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.

Link to publication: doi: 10.7554/eLife.48767

Link to Pubmed: PMID: 31710289

13) 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.

Link to publication: doi: 10.1093/humrep/dex263

Link to Pubmed: PMID: 28938739

14) 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.

Link to publication: doi:10.1038/ncomms15680

Link to Pubmed: PMID: 28604658

15) 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.

Link to publication: doi: 10.1093/humrep/dew271

Link to Pubmed: PMID: 27836978

16) He Z, Kee K*. (2017). Generating a Genome Editing Nuclease for Targeted Mutagenesis in Human Cells. Methods Mol Biol 1498: 153-162.

Link to publication: doi:10.1007/978-1-4939-6472-7_10

Link to Pubmed: PMID: 27709574

17) 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.

Link to publication: doi: 10.1038/nature19361

Link to Pubmed: PMID: 27626382

18) 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.

Link to publication: doi:10.1093/molehr/gaw040

Link to Pubmed: PMID: 27430550

19) 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.

Link to publication: doi: 10.1093/nar/gku1339

Link to Pubmed: PMID: 25541197

20) 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.

Link to publication: doi: 10.1016/j.stem.2011.01.013

Link to Pubmed: PMID: 21362567

21) 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.

Link to publication: doi: 10.1093/toxsci/kfq179

Link to Pubmed: PMID: 20562217

22) Kee K, Pera RA, Turek PJ*. (2010). Testicular germline stem cells. Nat Rev Urol 7(2): 94-100.

Link to publication: doi: 10.1038/nrurol.2009.263

Link to Pubmed: PMID: 20084076

23) 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.

Link to publication: doi: 10.1038/nature08562

Link to Pubmed: PMID: 19865085

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

Link to publication: doi: 10.1101/pdb.prot5048

Link to Pubmed: PMID: 21356917

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.

Link to publication: doi:10.1038/nbt1318

Link to Pubmed: PMID: 17572666

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.

Link to publication: doi: 10.1089/scd.2006.15.831

Link to Pubmed: PMID: 17253946

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.

Link to publication: doi: 10.1016/j.cell.2006.04.039

Link to Pubmed: PMID: 16814718

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.

Link to publication: doi: 10.1038/sj.emboj.7600184

Link to Pubmed: PMID: 15044957

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.

Link to publication: doi: 10.1016/s1097-2765(04)00063-2

Link to Pubmed: PMID: 14992724

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.

Link to publication: doi: 10.1093/genetics/160.1.111

Link to Pubmed: PMID: 11805049

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

Link to publication: doi: 10.1021/bi9716377

Link to Pubmed: PMID: 9521745