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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


个人简介

2005年获东北林业大学理学学士学位;2011年获北京大学理学博士学位;2011年至2016年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;2015年获NYSTEM Fellow; 2016年8月入职中科院生化与细胞所(现中科院极速快三官网),任研究员,研究组长,博士生导师。


研究方向

类器官模型与肿瘤靶向治疗


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,筛选区分恶性肿瘤的标记物;
    2) 体外重建不同时期的肿瘤类器官模型,研究肿瘤细胞及其微环境在不同阶段对靶向药物治疗拮抗的机制,研究肿瘤细胞可塑性与肿瘤抗药性的分子机理;
    3) 进一步优化前列腺癌、 胰腺癌、肺癌和胃肠道癌的类器官培养体系,建立来源于中国癌症病人的类器官模型库;
    4) 利用来源于病人的肿瘤类器官模型进行高通量药物筛选,发展新的抗癌药物;
    5) 组织器官的体外功能性构建。


代表性论文

(# equal contribution, * corresponding author)
  1. 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.  Nature Genetics. 2020 (in press)
  2. 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 Apr 6. pii: mjaa012. doi: 10.1093/jmcb/mjaa012. [Epub ahead of print]
  3. Tang D#, 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.
  4. Xia XY, Li F, He J, Aji R, Gao D*. Organoid technology in cancer precision medicine. Cancer Letters. 2019 Aug 10;457:20-27.
  5. 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.
  6. Zhang K#, Zhang L#,*, Liu W#, Ma X, Cen J, Sun Z, Wang C, Feng S, Zhang Z, Yue L, Sun L, Zhu Z, Chen X, Feng A, Wu J, Jiang Z, Li P, Cheng X, Gao D, Peng L*, Hui L*. In Vitro Expansion of Primary Human Hepatocytes with Efficient Liver Repopulation Capacity. Cell Stem Cell. 2018 Dec 6;23(6):806-819.e4.
  7. 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.
  8. 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.
  9. Wang SQ, Gao D, Chen Y*. The potential of organoids in urological cancer research. Nature Reviews Urology. 2017 Jul;14(7):401-414
  10. 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 Coordinate Regulation of PI3K/mTOR and AR Signaling. Cancer Cell. 2017 Mar 13;31(3):436-451.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. Gao D and Chen Y*. Organoid Development in Cancer Genome Discovery. Current Opinion in Genetics and Development. 2015 Mar 18; 30:42-48. (Invited Cover Review).
  16. 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: 176-187. 
  17. 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.
  18. 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. Nature Medicine. 2013 Aug; 19(8):1023-9. 11.

Link to a complete list of peer-reviewed publications: 


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