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邓宏魁

邮  箱: hongkui_deng@pku.edu.cn

职  称:教授

办公室地址:北京市海淀区颐和园路5号,北京大学,金光生命科学大楼,100871

实验室地址:北京市海淀区颐和园路5号,北京大学,金光生命科学大楼,100871

  • 个人简介
  • 科研领域
  • 代表性论文

个人介绍:

邓宏魁,北京大学博雅讲席教授、长江学者特聘教授,北京大学干细胞研究中心主任,清华-北大生命科学联合中心高级研究员,国家杰出青年科学基金获得者,973项目和国家重点研发计划首席科学家。课题组长期以来致力于开发调控细胞命运的新方法和建立多潜能干细胞制备的全新底层技术,累计发表论文160余篇,被引用16,000余次,尤其在小分子化合物诱导细胞命运转变方面做出了一系列开拓性工作:1)首次实现完全使用小分子化合物逆转“发育时钟”,让小鼠体细胞重新获得多潜能性(Science, 2013),在后续的研究工作中揭示了化学重编程全新的分子机制(Cell, 2015; Cell Stem Cell, 2018),一系列成果开创了全新的体细胞重编程体系;2) 首次实现完全使用小分子化合物诱导人类体细胞转变为多潜能干细胞(hCiPS细胞)(Nature, 2022),是我国从源头上独创的新一代多潜能干细胞制备技术;3)利用小分子化合物建立了一种全新的具有全能性特征的干细胞(EPS细胞)(Cell, 2017),从小鼠2细胞胚胎建立了新型全能性干细胞(TPS细胞)(Cell Res, 2022);4)利用小分子化合物实现功能成熟细胞在体外的长期维持(Science, 2019),从多潜能干细胞诱导制备功能成熟的肝细胞,在急性肝衰猪模型上成功完成了人工肝治疗的动物实验;从多潜能干细胞高效分化制备功能成熟的胰岛细胞,在糖尿病小鼠和猴模型上验证了有效性和安全性(Nature Medicine, 2022);5)实现小分子化合物诱导小鼠体细胞成为功能性神经元(Cell Stem Cell, 2015),并实现了在成年小鼠大脑中将体细胞原位转变神经元的体内重编程(Cell Discov, 2021)。

教育经历:

1990 - 1995 , 理学博士 , UCLA
1984 - 1987 , 理学硕士 , 上海第二医科大学
1980 - 1984 , 理学学士 , 武汉大学

荣誉奖励:

北京市科学技术一等奖(2011年)
药明康德生命化学研究杰出成就奖(2013年)
第七届“谈家桢生命科学奖”(2014年),
第十八届吴阶平-保罗·杨森医学药学奖(2017年)
中国干细胞年会干细胞杰出贡献奖(2018年)
中国细胞生物学学会杰出成就奖(2019年)
北京大学国华杰出学者奖(2019年)

工作经历:

1995-1997 美国纽约大学医学中心Skirball Institute,博士后研究
1998-2000 美国麻省ViaCell 公司,分子生物学主任
2001-至今  北京大学,特聘教授
2011-至今  北大-清华生命科学中心,高级研究员                          
2013-至今  北京大学干细胞研究中心,主任
2016-至今   北京大学博雅讲座教授

学术任职:

2010-2016 Board of Director, International Society for Stem Cell Research
2021-至今Board of Director, International Society for Regenerative Biology

  

杂志任职:

2013- Editorial Board Member, Cell 2013- Editorial Board Member, Cell Stem Cell 2013- Editorial Board Member, Stem Cell Report, 2010- Editorial Board Member, Cell Research
      本实验室主要兴趣在于体细胞重编程、细胞命运调控和再生医学应用研究。我们的主要研究方向是如何通过细胞命运调控获得多潜能干细胞和各种功能性细胞。生命的本质是化学过程,化学小分子调控细胞命运理论上是最有效的方式。我们研究团队建立了化学小分子调控细胞命运的技术手段,首次利用化学小分子将小鼠体细胞诱导成为多潜能干细胞和功能性神经元,首次实现完全利用化学小分子制备人多潜能干细胞,不仅有助于更好地理解细胞命运决定和转变机制,而且为未来再生医学治疗重大疾病带来新的可能。我们团队利用化学小分子首次在体外建立了具有全能性特征的干细胞(EPS细胞),该细胞具有更强的发育潜能,为体外制备各种功能成熟的细胞类型提供了更好的来源。我们将利用多潜能干细胞定向分化制备功能性的血液细胞、胰岛细胞、肝脏细胞,并结合基因编辑技术制备新型抗肿瘤的CAR-T细胞,为治疗重大疾病提供新的解决方案。



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2. Xu Y, Zhao J, Ren Y, Wang X, Lyu Y, Xie B, Sun Y, Yuan X, Liu H, Yang W, Fu Y, Yu Y, Liu Y, Mu R, Li C, Xu J, Deng H. Derivation of totipotent-like stem cells with blastocyst-like structure forming potential. Cell Res. 2022 Jun;32(6):513-529.

3. Du Y, Liang Z, Wang S, Sun D, Wang X, Liew SY, Lu S, Wu S, Jiang Y, Wang Y, Zhang B, Yu W, Lu Z, Pu Y, Zhang Y, Long H, Xiao S, Liang R, Zhang Z, Guan J, Wang J, Ren H, Wei Y, Zhao J, Sun S, Liu T, Meng G, Wang L, Gu J, Wang T, Liu Y, Li C, Tang C, Shen Z, Peng X, Deng H. Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates. Nat Med. 2022 Feb;28(2):272-282.

4. Wang Y, Liu L, Song Y, Yu X, Deng H. Unveiling E2F4, TEAD1 and AP-1 as regulatory transcription factors of the replicative senescence program by multi-omics analysis. Protein Cell. 2022 Jan 12. doi: 10.1007/s13238-021-00894-z

5. Lai W, Xie H, Liu Y, Zheng F, Zhang Y, Lei Q, Lv L, Dong J, Song J, Gao X, Yin M, Wang C, Deng H.Human pluripotent stem cell-derived eosinophils reveal potent cytotoxicity against solid tumors. Stem Cell Reports. 2021 Jul 13;16(7):1697-1704.

6. Liu B, Chen S, Xu Y, Lyu Y, Wang J, Du Y, Sun Y, Liu H, Zhou H, Lai W, Xue A, Yin M, Li C, Bai Y, Xu J, Deng H. Chemically defined and xeno-free culture condition for human extended pluripotent stem cells. Nat Commun. 2021 May 21;12(1):3017.

7. Qu M, Xiong L, Lyu Y, Zhang X, Shen J, Guan J, Chai P, Lin Z, Nie B, Li C, Xu J, Deng H. Establishment of intestinal organoid cultures modeling injury-associated epithelial regeneration. Cell Res. 2021 Mar;31(3):259-271.

8. Ma Y, Xie H, Du X, Wang L, Jin X, Zhang Q, Han Y, Sun S, Wang L, Li X, Zhang C, Wang M, Li C, Xu J, Huang Z, Wang X, Chai Z, Deng H. In vivo chemical reprogramming of astrocytes into neurons. Cell Discov. 2021 Mar 2;7(1):12.

9. Lu S, Zhao J, Dong J, Liu H, Zhu Y, Li H, Liu L, Yang Y, Sun S, Song Y, Zhao Y, She R, Luo T, Deng H, Peng X. Effective treatment of SARS-CoV-2-infected rhesus macaques by attenuating inflammation. Cell Res. 2021 Feb;31(2):229-232

10. Cai Y, Zhou H, Zhu Y, Sun Q, Ji Y, Xue A, Wang Y, Chen W, Yu X, Wang L, Chen H, Li C, Luo T, Deng H. Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice. Cell Res. 2020 Jul;30(7):574-589.

11. Wang Q, Sun D, Liang Z, Wang J, Zhong X, Lyu Y, Cao J, Lin Z, Du Y, Miao Z, Lu S, Li C, Xu J, Shi Y, Deng H. Generation of human hepatocytes from extended pluripotent stem cells. Cell Res. 2020 Sep;30(9):810-813.

12. Deng C, Zhao J, Zhou S, Dong J, Cao J, Gao J, Bai Y, Deng H. The Vascular Disrupting Agent CA4P Improves the Antitumor Efficacy of CAR-T Cells in Preclinical Models of Solid Human Tumors. Mol Ther. 2020 Jan 8;28(1):75-88.

13. Chen S, Wang J, Ren H, Liu Y, Xiang C, Li C, Lu S, Shi Y, Deng H, Shi X. Hepatic spheroids derived from human induced pluripotent stem cells in bio-artificial liver rescue porcine acute liver failure. Cell Res. 2020 Jan;30(1):95-97.

14. Xu L, Wang J, Liu Y, Xie L, Su B, Mou D, Wang L, Liu T, Wang X, Zhang B, Zhao L, Hu L, Ning H, Zhang Y, Deng K, Liu L, Lu X, Zhang T, Xu J, Li C, Wu H, Deng H, Chen H. CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia. N Engl J Med. 2019 Sep 26;381(13):1240-1247.

15. Xiang C, Du Y, Meng G, Soon Yi L, Sun S, Song N, Zhang X, Xiao Y, Wang J, Yi Z, Liu Y, Xie B, Wu M, Shu J, Sun D, Jia J, Liang Z, Sun D, Huang Y, Shi Y, Xu J, Lu F, Li C, Xiang K, Yuan Z, Lu S, Deng H. Long-term functional maintenance of primary human hepatocytes in vitro. Science. 2019 Apr 26;364(6438):399-402.

16. Xie B, Sun D, Du Y, Jia J, Sun S, Xu J, Liu Y, Xiang C, Chen S, Xie H, Wang Q, Li G, Lyu X, Shen H, Li S, Wu M, Zhang X, Pu Y, Xiang K, Lai W, Du P, Yuan Z, Li C, Shi Y, Lu S, Deng H. A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts. Cell Res. 2019 Sep;29(9):696-710.

17. Zhao T, Fu Y, Zhu J, Liu Y, Zhang Q, Yi Z, Chen S, Jiao Z, Xu X, Xu J, Duo S, Bai Y, Tang C, Li C, Deng H. Single-Cell RNA-Seq Reveals Dynamic Early Embryonic-like Programs during Chemical Reprogramming. Cell Stem Cell. 2018 Jul 5;23(1):31-45.

18. Li X, Xu J, Deng H. Small molecule-induced cellular fate reprogramming: promising road leading to Rome. Curr Opin Genet Dev. 2018 May 29; 52:29-35.

19. Yang Y, Liu B, Xu J, Wang J, Wu J, Shi C, Xu Y, Dong J, Wang C, Lai W, Zhu J, Xiong L, Zhu D, Li X, Yang W, Yamauchi T, Sugawara A, Li Z, Sun F, Li X, Li C, He A, Du Y, Wang T, Zhao C, Li H, Chi X, Zhang H, Liu Y, Li C, Duo S, Yin M, Shen H, Belmonte JC, Deng H. Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency. Cell. 2017;169(2):243-257.

20. Li X, Liu D, Ma Y, Du X, Jing J, Wang L, Xie B, Sun D, Sun S, Jin X, Zhang X, Zhao T, Guan J, Yi Z, Lai W, Zheng P, Huang Z, Chang Y, Chai Z, Xu J, Deng H. Direct Reprogramming of Fibroblasts via a Chemically Induced XEN-like State. Cell Stem Cell. 2017 Aug 3;21(2):264-273.

21. Xu L, Yang H, Gao Y, Chen Z, Xie L, Liu Y, Liu Y, Wang X, Li H, Lai W, He Y, Yao A, Ma L, Shao Y, Zhang B, Wang C, Chen H, Deng H. CRISPR/Cas9-Mediated CCR5 Ablation in Human Hematopoietic Stem/Progenitor Cells Confers HIV-1 Resistance In Vivo. Mol Ther. 2017 Aug 2;25(8):1782-1789.

22. Ye J, Ge J, Zhang X, Cheng L, Zhang Z, He S, Wang Y, Lin H, Yang W, Liu J, Zhao Y, Deng H. Pluripotent stem cells induced from mouse neural stem cells and small intestinal epithelial cells by small molecule compounds. Cell Res. 2016; 26:34-45.

23. Zhao Y, Zhao T, Guan J, Zhang X, Fu Y, Ye J, Zhu J, Meng G, Ge J, Yang S, Cheng L, Du Y, Zhao C, Wang T, Su L, Yang W, Deng H. A XEN-like State Bridges Somatic Cells to Pluripotency during Chemical Reprogramming, Cell. 2015; 163, 1678-91.

24. Li X, Zuo X, Jing J, Ma Y, Wang J, Liu D, Zhu J, Du X, Xiong L, Du Y, Xu J, Xiao X, Wang J, Chai Z, Zhao Y, Deng H. Small-Molecule-Driven Direct Reprogramming of Mouse Fibroblasts into Functional Neurons. Cell Stem Cell. 2015; 17:195-203.


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27. Du Y, Wang J, Jia J, Song N3 Xiang C, Xu J, Hou Z, Su X, Liu B, Jiang T, Zhao D, Sun Y, Shu J, Guo Q, Yin M, Sun D, Lu S, Shi Y, Deng H. Human hepatocytes with drug metabolic function induced from fibroblasts by lineage reprogramming. Cell Stem Cell. 2014; 14:394-403.

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