首页 全所PI名录
  • 高栋
  • 研究员,研究组长,博士生导师
  • E-mail: dong.gao@@sibcb.ac.cn
  • 实验室主页: http://www.sibcb.ac.cn/gaolab/
    个人简介:
  •   2005年毕业于东北林业大学,获理学学士学位;2011年毕业于北京大学,获理学博士学位。2011年8月至2016年7月先后在美国约翰霍普金斯大学和纪念斯隆凯特琳癌症研究所从事肿瘤生物学博士后研究;2016年8月受聘于中科院上海生化与细胞所,任研究员、研究组长、博士生导师。

    社会任职:
  •  
    研究方向:
  • 类器官构建与肿瘤等疾病研究
    研究工作:
  •   我们以正常组织类器官、肿瘤类器官、小鼠模型和临床肿瘤标本为基础,运用分子细胞生物学的实验手段,研究成体干细胞和肿瘤祖细胞的分子调控网络以及肿瘤细胞抗药性的分子机理。目前的主要研究内容包括:

      1) 研究成体干细胞和肿瘤祖细胞,寻找维持成体干细胞多能性的主要调控基因;

      2) 组织器官的体外功能性构建;

      3) 体外重建不同时期的肿瘤类器官模型,研究肿瘤细胞可塑性与肿瘤抗药性的分子机理;

      4) 建立来源于中国癌症病人的类器官模型库,进行高通量药物筛选,发展新的抗癌药物。

    承担科研项目情况:
    代表论著:
    1. Han M#, Li F#,*, Zhang YH#, Dai PF, He J, Li YG, Zhu YQ, Zheng JK, Huang H, Bai F, Gao D*. FOXA2 drives lineage plasticity and Kit pathway activation in neuroendocrine prostate cancer. Cancer Cell. 2022 Nov 3;40, 1–18
    2. Peng JY#, Li F#, Wang J, Wang CX, Jiang YA, He J, Yuan K, Bei JX, Wang V, Zhou B, Chen LN, Gao D*, Zhao Y*. Identification of a rare Gli1+ progenitor cell population contributing to liver regeneration during chronic injury. Cell Discovery. 2022 Nov 1;8(1):118.
    3. He J#, Cui HY#, Shi XH, Jin QQ, Han XM, HTT, Peng JY, Guo SW, Zhao Y, Zhou B, Chen LN, Chen L, Zeng YA, Wang HY*, Jin G*, Gao D*. Functional hepatobiliary organoids recapitulate liver development and reveal essential drivers of hepatobiliary cell fate determination. Life Medicine. 2022 (accepted)
    4. Wang WW#,  Ma LL#, Zheng X#, Yuan TG, Bao JX, Zhu YJ, Zhao XF, Zhao Y, Zong YL, Zhang YN, Shen SY, Qiu XY, Yang S, Wang HY*, Gao D*, Wang P*, Chen L*. Tumor specific circRNA-derived neoantigen peptide identification for hepatobiliary tumor. Engineering. 2022 DOI: 10.1016/j.eng.2022.06.008
    5. Wang YQ, Zhang LP, Liu Y, Tang LL, He J, Sun XQ, Younis MH, Cui DX, Xiao HH, Gao D*, Kong XY*, Cai WB*, Song J*. Engineering CpG-ASO-Pt-loaded Macrophages (CAP@M) For Synergistic Chemo-/Gene-/Immuno-Therapy. Adv Healthc Mater. 2022 Aug;11(15):e2201178.
    6. Wang WW#, Yuan TG#,  Ma LL#, Zhu YJ#, Bao JX, Zhao XF, Zhao Y, Zong YL, Zhang YN, Yang S, Qiu XY, Shen SY, Wu R, Wu T, Wang HY*, Gao D*, Wang P*, Chen L*. Hepatobiliary tumor organoids reveal HLA I neoantigen landscape and antitumoral activity of neoantigen peptide enhanced with ICIs. Adv Sci (Weinh). 2022 Aug;9(22):e2105810.
    7. Tang FY#, Xu D#, Wang SQ#, Wong CK#, Fundichely AM, Lee CJ, Cohen S, Park J, Hill CE, Eng K, Bareja R, Han T, Liu EM, Palladino A, Di W, Gao D, Abida W, Beg S, Puca L, Meneses M, Stanchina E, Berger MF, Gopalan A, Dow L,  Mosquera JM, Beltran H, Sternberg CN, Chi P, Scher HI, Sboner A, Chen Y*, Ekta Khurana E*. Chromatin profiles classify castration-resistant prostate cancers suggesting therapeutic targe. Science. 2022 May 27;376(6596):eabe1505.
    8. Shi XH#, Li YG#, Yuan QY#, Tang SJ#, Guo SW#, Zhang YH, He J, Zhang XY, Han M, Liu Z, Zhu YQ, Gao SZ, Wang H, Xu XF, Zheng KL, Jing W, Chen LN*, Wang Y*, Jin G*, Gao D*. Integrated profiling of human pancreatic cancer organoids reveals chromatin accessibility to drug sensitivity networks. Nat Commun. 2022 Apr 21;13(1):2169.
    9. Gu YQ#, Cao J#, Zhang XY#, Gao H#, Wang YY#, Wang J#, He J#, Jiang XY#, Zhang JL, Shen GH, Yang J, Zheng XC, Hu GW, Zhu YF, Du SJ, Zhu YK, Zhang R, Xu JQ, Zhang CC, Lan F, Qu D, Xu GL, Zhao Y*, Gao D*, Xie YH*, Luo M*, Lu ZG*. Receptome profiling identifies KREMEN1 and ASGR1 as alternative functional receptors of SARS-CoV-2. Cell Res. 2022 Jan;32(1):24-37.
    10. Fu X#, He Q#, Tao Y#, Wang DM#, Wang W#, Wang YL#, Yu QC#, Zhang F#, Zhang XY#, Chen YG*, Gao D*, Hu P*, Hui LJ*, Wang XQ*, Zeng YA*. Recent advances in tissue stem cells. Sci China Life Sci. 2021 Dec;64(12):1998-2029.
    11. Zhao Y#, Li ZX#, Zhu YJ#, Fu J#, Zhao XF, Zhang YN, Wang S, Wu JM, Wang KT, Wu R, Sui CJ, Shen SY, Wu X, Wang HY*, Gao D*, Chen L*. Single cell transcriptome analysis uncovers intra-tumoral heterogeneity and underlying mechanisms for drug resistance in hepatobiliary tumor organoids. Adv Sci (Weinh). 2021 Jun;8(11):e2003897.
    12. Li F#, Han M#, Dai PF#, Xu W#, He J#, Tao XT#, Wu Y#, Tong XY, Xia XY, Guo WX, Zhou YJ, Li YG, Zhu YQ, Zhang XY, Liu Z, Aji R, Cai X, Li YT, Qu D, Chen Y, Jiang SB, Wang Q, Ji HB, Xie YH*, Sun YH*, Lu L*, Gao D*. Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide. Nat Commun. 2021 Feb 8;12(1):866.
    13. Dhimolea E*, de Matos Simoes R, Kansara D, Al'Khafaji A, Bouyssou J, Weng X, Sharma S, Raja J, Awate P, Shirasaki R, Tang H, Glassner BJ, Liu ZY, Gao D, Bryan J, Bender S, Roth J, Scheffer M, Jeselsohn R, Gray NS, Georgakoudi I, Vazquez F, Tsherniak A, Chen Y, Welm A, Duy C, Melnick A, Bartholdy B, Brown M, Culhane AC, Mitsiades CS*. An embryonic diapause-like state with suppressed Myc activity enables tumor treatment persistence. Cancer Cell. 2021 Feb 8;39(2):240-256.e11.
    14. Li F#, Yuan QY#, Di W#, Xia XY#, Liu Z, Mao NH, Li L, Li CF, He J, Li YG, Guo WX, Zhang XY, Zhu YQ, Aji R, Wang SQ, Chi P, Carver B, Wang Y*, Chen Y*, Gao D*. ERG orchestrates chromatin interactions to drive prostate cell fate reprogramming. J Clin Invest. 2020 Nov 2;130(11):5924-5941.
    15. Guo WX#, Li L#, He J, Liu Z, Han M, Li F, Xia XY, Zhang XY, Zhu Y, Wei Y, Li YG, Aji R, Dai H, Wei H, Li CF, Chen Y*, Chen LN*, Gao D*. Single-cell transcriptomics identifies a distinct luminal progenitor cell type in distal prostate invagination tips.  Nat Genet. 2020 Sep;52(9):908-918.
    16. He J, Zhang X, Xia XY, Han M, Li F, Li CF, Li YG, Gao D*. Organoid technology for tissue engineering. J Mol Cell Biol. 2020 Aug 1;12(8):569-579. (Invited review)
    17. Tang J#, Wang HX#, Huang XZ#, Li F#, Zhu H, Li Y, He LJ, Zhang H, Pu WJ, Liu K, Zhao H, Bentzon JF, Yu Y, Ji Y, Nie Y, Zhang L*, Gao D*, Zhou B*. Sca1+ Vascular Stem Cells Contribute to Smooth Muscle for Artery Repair and Regeneration. Cell Stem Cell. 2020 Jan 2;26(1):81-96.
    18. Xia XY, Li F, He J, Aji R, Gao D*. Organoid technology in cancer precision medicine. Cancer Lett. 2019 Aug 10;457:20-27. (Invited review)
    19. Ding YF#, Li N#, Dong BJ#, Guo WX, Wei H, Chen QL, Yuan HR, Han Y, Chang HW, Kan S, Wang XG, Pan Q, Wu P, Peng C, Qiu T, Li QT, Gao D*, Xue W*, Qin J*. Chromatin remodeling ATPase BRG1 and PTEN are synthetic lethal in prostate cancer. J Clin Invest. 2019 Feb 1;129(2):759-773.
    20. Kim SM, Nguyen TT, Ravi A, Kubiniok P, Finicle BT, Jayashankar V, Malacrida L, Hou J, Robertson J, Gao D, Chernoff J, Digman MA, Potma EO, Tromberg BJ, Thibault P, Edinger AL*. PTEN deficiency and AMPK activation promote nutrient scavenging and anabolism in prostate cancer cells. Cancer Discovery. 2018 Jul;8(7):866-883.
    21. Viswanathan VS, Ryan MJ, Dhruv HD, Gill S, Eichhoff OM, Seashore-Ludlow B, Kaffenberger SD, Eaton JK, Shimada K, Andrew J. Aguirre AJ, Viswanathan SR, Tamayo P, Yang WS, Rees MG, Chen SX, Boskovic ZV, Javaid S, Huang C, Wu XY, Tseng YY, Roider EM, Gao D, Cleary JM, Wolpin BM, Mesirov JP, Daniel A. Haber DA, Engelman JA, Boehm JS, Kotz JD, Hon CS, Chen Y, Hahn WC, Levesque MP, Doench JG, Berens ME, Shamji AF, Clemons PA, Stockwell BR & Schreiber SL*. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature. 2017 Jul 27;547(7664):453-457.
    22. Blattner M, Liu D, Robinson BD, Huang D, Poliakov A, Gao D, Nataraj S, Deonarine LD, Augello MA, Sailer V, Ponnala L, Ittmann M, Chinnaiyan AM, Sboner A, Chen Y, Rubin MA*, Barbieri CE*. SPOP Mutation Drives Prostate Tumorigenesis In Vivo through Coordinates Regulation of PI3K/mTOR and AR Signaling. Cancer Cell. 2017 Mar 13;31(3):436-451.
    23. Mu P, Zhang Z, Benelli M, Karthaus WR, Hoover E, Chen CC, Wongvipat J, Ku SY, Gao D, Cao Z, Shah N, Adams EJ, Abida W, Watson PA, Prandi D, Huang CH, de Stanchina E, Lowe SW, Ellis L, Beltran H, Rubin MA, Goodrich DW, Demichelis F, Sawyers CL*. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science. 2017 Jan 6;355(6320):84-88.
    24. Dardenne E#, Beltran H#, Benelli M, Gayvert K, Berger A, Puca L, Cyrta J, Sboner A, Noorzad Z, MacDonald T, Cheung C, Gao D, Chen Y, Eilers M, Mosquera JM, Robinson BD, Elemento O, Rubin MA, Francesca Demichelis F and Rickman DS*. N-Myc induces an EZH2-mediated transcriptional program driving neuroendocrine prostate cancer. Cancer Cell. 2016 Oct; 30:563-577.
    25. Wiesner T, Lee W, Obenauf A, Ran L, Murali R, Zhang Q, Wong E, Hu W, Sasinya S,  Shah R, Scott S, Sboner A, Button J, Landa I, Gao D, Cao Z, Shukla S, , Merghoub T, Schwartz G, Wang L, Ladanyi M, Fagin J, Hollmann T, Busam K, BergerM , Chen Y* and Chi P*. Alternative transcription initiation leads to expression of a novel ALK isoform in cancer. Nature. 2015 Oct 15;526(7573):453-7.
    26. Ran LL, Sirota I, Cao Z, Murphy D, Chen YD, Shukla S, Xie YY, Gao D, Zhu S, Rossi F, Wongvipat J, Taguchi T, Tap WD, Mellinghoff IK, Besmer P, Antonescu CR, Chen Y* and Chi P*. Combined inhibition of MAP kinase and KIT signaling pathways destabilizes the ETV1 protein and synergistically suppress GIST tumorigenesis. Cancer Discovery. 2015 Mar;5(3):304-15.
    27. Gao D and Chen Y*. Organoid Development in Cancer Genome Discovery. Curr Opin Genet Dev. 2015 Mar 18; 30:42-48. (Invited Cover Review)
    28. Gao D#, Vela I#, Sboner A#, Iaquinta PJ#, Karthaus WL, Gopalan A, Wanjala JN, Dowling C, Undvall EA, Wongvipat J, Kossai M, Barboza LP, Di W, Cao Z, Zhang QF, Sirota I, Ran Ll, Solomon SB, MacDonald TY, Beltran H, Mosquera J,  Eastham JA, Touijer KA, Scardino PT, Laudone VP, Rathkopf DE, Morris MJ, Danila DC, Slovin SF, Chi P, Clevers H, Carver B, Rubin MA, Scher HI, Sawyers CL*, Chen Y*. Generation of in vitro organoids cultures derived from patients with advanced prostate cancer. Cell. 2014 Sep; 159(1): 176-187.
    29. Karthaus WR, Iaquinta PJ, Drost J, Gracanin A, Wongvipat J, Gao D, Befthel H, Sachs N, Vries RG.J, Cuppen E, Chen Y, Sawyers CL and Clevers H*. Identification of multipotent luminal progenitor cells in human prostate organoid cultures. Cell. 2014 Sep; 159: 163-175.  
    30. Chen Y*, Chi P, Rockowitz S, Iaquinta P.J, Shamu T, Shukla S, Gao D, Sirota I, Carver B.S, Wongvipat J, Scher H.I, Zheng D, Sawyers CL*.  ETS factors reprogram the androgen receptor cistrome and prime prostate tumorigenesis in response to PTEN loss. Nat Med. 2013 Aug; 19(8):1023-9. 11.
    获奖及荣誉:
    研究组成员:
  • 合影