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科研PI

邓宏魁教授

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一、个人简介:

1980 – 1984年 毕业于武汉大学,获得理学学士学位

1984 – 1987年 毕业于上海第二医科大学,获得理学硕士学位

1990 - 1995年 毕业于美国加州大学洛杉矶分校(UCLA),获得免疫学博士学位

1995 - 1997年 于纽约大学DAN LITTERMAN院士实验室从事博士后研究工作;期间发现了HIV的关键共受体CCR5

1998-2000年 在美国麻省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,细胞生物学系主任,博士生导师

2016 - 至今 北京大学博雅讲席教授

邓宏魁,北京大学博雅讲席教授,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。2010-2016年当选为国际干细胞生物学学会(ISSCR)理事会理事,现为国际再生生物学学会(ISRB)理事。多年来邓宏魁教授主要从事干细胞和再生医学研究,首次建立了利用化学小分子诱导多能干细胞(CiPS)技术,在Nature、Science、Cell、Cell Stem Cell等期刊累计发表论文170余篇,被引用18,000余次,经过多年的不懈努力,邓宏魁教授团队在化学小分子调控细胞命运的研究中取得多项突破性、原创性成果,为细胞命运的改变提供了新的思路,开创了化学重编程和制备功能细胞的新方法,为未来应用于再生医学领域,为治愈重大疾病提供新的解决方案。

二、研究成果:

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)

2. 发现促进分化的关键基因可以替代多潜能性关键基因,实现体细胞重编程,与汤超研究组合作提出细胞命运决定的“跷跷板模型”(Cell, 2013)

3. 建立了一套更高效的利用小分子化合物诱导化学多潜能干细胞(CiPS细胞)的方案(Cell, 2015),揭示了化学重编程不同于传统重编程的分子机制

4. 实现化学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)

5. 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)

6. 完成了世界首例基于基因编辑干细胞治疗艾滋病和白血病的案例,证明了CRISPR基因编辑技术临床应用的安全性(NEJM, 2019)

7. 利用化学小分子调控的手段实现了人成体肝细胞在体外的长期维持(Science, 2019),在急性肝衰猪模型上成功完成了基于多能干细胞技术构建的新型生物人工肝治疗重症肝病的临床前研究(Cell Research, 2020)

8. 利用人CiPS细胞高效分化制备功能成熟的胰岛细胞,在糖尿病猴模型上验证了有效性和安全性(Nature Medicine, 2022, Nature Metabolism, 2023)

9. 在成年小鼠大脑中将神经胶质细胞原位转变神经元的体内重编程(Cell Discovery, 2021)

10. 利用化学小分子从小鼠2细胞胚胎建立了新型全能性干细胞(TPS细胞)(Cell Research, 2022)

11. 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)

三、奖励:

2013年 获得药明康德生命化学杰出成就奖(Wuxi PharmaTech Life Science Outstanding Achievements Awards)

2014年 获得谭家帧生命科学成就奖

2017 年 获得吴阶平-保罗·杨森医学药学奖(WuJieping-Paul Janssen Medical & Pharmaceutical Award)

2019年 邓宏魁教授入选英国《自然》杂志全球十大科学人物

2023年 获得第八届“中源协和生命医学成就奖”

四、代表性研究论文:

1. Lv Y, Rao Z, Liu L, Jia J, Wu C, Xu J, Du Y, Liu Y, Liu B, Shi J, Li G, Zhao D, Deng H. The efficient generation of functional human hepatocytes from chemically induced pluripotent stem cells. Cell Prolif. 2023 Oct 9: e13540.

2. Wang G, Wang Y, Lyu Y, He H, Liuyang S, Wang J, Sun S, Cheng L, Fu Y, Zhu J, Zhong X, Yang Z, Chen Q, Li C, Guan J, Deng H. Chemical-induced epigenome resetting for regeneration program activation in human cells. Cell Rep. 2023 Jun27;42(6):112547.

3. Liuyang S, Wang G, Wang Y, He H, Lyu Y, Cheng L, Yang Z, Guan J, Fu Y, Zhu J,Zhong X, Sun S, Li C, Wang J, Deng H. Highly efficient and rapid generation of human pluripotent stem cells by chemical reprogramming. Cell Stem Cell. 2023 Apr6;30(4):450-459.e9.

4. Liang Z, Sun D, Lu S, Lei Z, Wang S, Luo Z, Zhan J, Wu S, Jiang Y, Lu Z, Sun S, Shi Y, Long H, Wei Y, Yu W, Wang Z, Yi LS, Zhang Y, Sun W, Fang X, Li Y, Lu S, Lv J, Sui W, Shen Z, Peng X, Du Y, Deng H. Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets. Nat Metab. 2023 Jan;5(1):29-40.

5. Wang J, Sun S, Deng H. Chemical reprogramming for cell fate manipulation: Methods, applications, and perspectives. Cell Stem Cell. 2023 Sep 7;30(9):1130-1147.

6. 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 multiomics analysis. Protein Cell. 2022 Oct;13(10):742-759.

7. Guan J, Wang G, Wang J, Zhang Z, Fu Y, Cheng L, Meng G, Lyu Y, Zhu J, Li Y,Wang Y, Liuyang S, Liu B, Yang Z, He H, Zhong X, Chen Q, Zhang X, Sun S, Lai W,Shi Y, Liu L, Wang L, Li C, Lu S, Deng H. Chemical reprogramming of human somatic cells to pluripotent stem cells. Nature. 2022 May;605(7909):325-331.

8. 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.

9. 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.

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

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. Du Y, Wang T, Xu J, Zhao C, Li H, Fu Y, Xu Y, Xie L, Zhao J, Yang W, Yin M, Wen J, Deng H. Correction to: Efficient derivation of extended pluripotent stem cells from NOD-scid Il2rg-/- mice. Protein Cell. 2019 Feb;10(2):154-155.

19. 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.

20. Du Y, Wang T, Xu J, Zhao C, Li H, Fu Y, Xu Y, Xie L, Zhao J, Yang W, Yin M, Wen J, Deng H. Efficient derivation of extended pluripotent stem cells from NOD-scid Il2rg-/- mice. Protein Cell. 2019 Jan;10(1):31-42.

21. Li H, Zhao C, Xu J, Xu Y, Cheng C, Liu Y, Wang T, Du Y, Xie L, Zhao J, Han Y, Wang X, Bai Y, Deng H. Rapid generation of gene-targeted EPS-derived mouse models through tetraploid complementation. Protein Cell. 2019 Jan;10(1):20-30.

22. 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.

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

24. 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. e 7.

25. 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 JCI, Deng H. Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency. Cell. 2017 Apr 6;169(2):243-257.e25.

26. 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.

27. 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.e7.

28. Zhao T, Li Y, Deng H. Cell fate conversion-from the viewpoint of small molecules and lineage specifiers. Diabetes Obes Metab. 2016 Sep;18 Suppl 1:3-9.

29. 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 Aug 6;17(2):195-203.

30. Xu J, Du Y, Deng H. Direct lineage reprogramming: strategies, mechanisms, and applications. Cell Stem Cell. 2015 Feb 5;16(2):119-34.

31. Liu K, Fang R, Li H, Yang W, Miao Z, Wen J, Deng H. Efficient derivation of embryonic stem cells from NOD-scid Il2rg (-/-) mice. Protein Cell. 2015 Dec;6(12):916-8.

32. 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 Dec17;163(7):1678-91.

33. Fang R, Liu K, Zhao Y, Li H, Zhu D, Du Y, Xiang C, Li X, Liu H, Miao Z, Zhang X, Shi Y, Yang W, Xu J, Deng H. Generation of naive induced pluripotent stem cells from rhesus monkey fibroblasts. Cell Stem Cell. 2014 Oct 2;15(4):488-497.

34. Du Y, Wang J, Jia J, Song N, 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 Mar 6;14(3):394-403.

35. Hou P, Li Y, Zhang X, Liu C, Guan J, Li H, Zhao T, Ye J, Yang W, Liu K, Ge J, Xu J, Zhang Q, Zhao Y, Deng H. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science. 2013 Aug 9;341(6146):651-4.

36. Shu J, Wu C, Wu Y, Li Z, Shao S, Zhao W, Tang X, Yang H, Shen L, Zuo X, Yang W, Shi Y, Chi X, Zhang H, Gao G, Shu Y, Yuan K, He W, Tang C, Zhao Y, Deng H. Induction of pluripotency in mouse somatic cells with lineage specifiers. Cell. 2013 May 23;153(5):963-75.

37. Shu J, Deng H. Lineage specifiers: new players in the induction of pluripotency. Genomics Proteomics Bioinformatics. 2013 Oct;11(5):259-63.

五、联系方式

Email :  hongkui_deng@pku.edu.cn