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院士风采
杰出青年
全所PI名录
 
 
地址:上海市岳阳路320号
邮编:200031
电话:86-21-54920000
传真:86-21-54921011
邮箱:sibcb@sibcb.ac.cn

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年毕业于东北林业大学,获生物技术专业学士学位;2011年毕业于北京大学,获细胞生物学专业博士学位;2011年至2016年先后在美国约翰霍普金斯大学 (The Johns Hopkins University) 和纪念斯隆凯特琳癌症研究所 (Memorial Solan Kerttering Cancer Center) 接受博士后训练,从事肿瘤生物学研究;2015年获选纪念斯隆凯特琳癌症研究所NYSTEM Fellow;2016年8月全职回中科院生物化学与细胞生物学研究所工作,任研究员,研究组长,博士生导师。


研究方向

细胞的可塑性与肿瘤治疗


研究工作
  目前癌症病人的个性化治疗和精准治疗成为全世界医学研究的热点,而能够维持癌细胞在体内特征的癌症体外模型匮乏已成为癌症病人个性化治疗和精准治疗研究的瓶颈。我们构建了前列腺肿瘤类器官 (Patients derived organoids,PDO) 培养体系,将前列腺肿瘤细胞体外培养的效率从几乎为0提高到了20%,首次报道了前列腺癌血液循环肿瘤细胞的类器官培养模型。肿瘤类器官模型最大限度的维持了肿瘤细胞在体内特征, 并且可以作为高通量药物筛选平台,将会在癌症病人的个性化治疗和精准治疗领域发挥巨大的作用。
        我们以前列腺正常组织细胞类器官、肿瘤类器官和肿瘤小鼠模型为基础,运用分子细胞生物学的实验手段,研究前列腺成体干细胞和前列腺癌祖细胞的分子调控网络和肿瘤细胞抗药性的分子机理。我们实验室的长期目标是利用类器官模型探索肿瘤的个性化治疗。实验室的主要研究方向包括:

        1)研究前列腺成体干细胞和前列腺癌祖细胞,寻找维持成体干细胞多能性的主要调控基因,筛选区分恶性前列腺癌的标记物;
        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;
        3)肿瘤细胞可塑性与肿瘤抗药性的分子机理研究;
        4)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;
        5)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。


代表性论文

(*equal contribution, # corresponding author)
  1.  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.
  2.  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.
  3. Yang ZH, Peng YC, Gopalan A, Gao D, Chen Y, Joyner AL. Stromal Hedgehog signaling maintains smooth muscle and hampers micro-invasive prostate cancer. Disease Models & Mechanisms. 2016 : doi: 10.1242/dmm.027417
  4.  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.
  5. Gao D#, Zhan Y, Di W, Moore AR, Sher JJ, Guan YX, Wang SQ, Zhang ZD, Murphy DA, Sawyers CL, Chi P and Chen Y#. A Tmprss2-CreERT2 knock-in mouse model for cancer genetic studies on prostate and colon. PLoS One 11(8): e0161084.
  6. Drost J*, Karthaus WR*, Gao D, Driehuis E, Sawyers CL, Chen Y and Clevers H#. Organoid culture systems for prostate epithelial tissue and prostate cancer tissue.  Nature Protocols. 2016 Jan; Doi:10.1038/347–358.
  7. 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;Doi:10.103811.
  8. Ran LL, SirotaI, 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 Jan; DOI: 10.1158/2159-829011.
  9.  Gao D and ChenY#.Organoid Development in Cancer Genome Discovery. Current Opinion in Genetics and Development. 2015 Mar 18; 30:42-48. (Invited Cover Review).
  10. 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. 
  11.  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 luminal stem cells in the human prostate using a novel epithelial culture system. Cell, 2014 Sep; 159: 163-175.
  12. Zeng Y#, Gao D, Kim JJ, Shiraishi T, Terada N, Kakehi Y, Kong CZ, Getzenberg RH, Kulkarni P#. Prostate-associated gene 4 (PAGE4) protects cells against stress by elevating p21 and suppressing reactive oxygen species production. American Journal of Clinical and Experimental Urology, 2013 Dec; 1(1):39-52.11.
  13. 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.
  14. Zeng Y#, Wodzenski D, Gao D, Shiraishi T, Terada N, Li Y, Griend D.J.V, Luo J, Kong C, Getzenberg R.H, Kulkarni P#. Stress-response protein RBM3 attenuates the stem-like properties of prostate cancer cells by interfering with CD44 variant splicing.Cancer Research. 2013 Jul; 73(13): 4123-4133.11.
  15. Yang YK, Qu H, Gao D, Zhai ZH, and Chen DY#. ARF-like protein 16(ARL16) inhibits RIG-I by binding with CTD in GTP dependent manner. J. Biol. Chem. 2011, 286: 10568-10580.11
  16. Gao D, Yang YK, Wang RP, Zhou X, Diao FC, Li MD, Zhai ZH, Jiang ZF, and Chen DY#.  REUL is a novel E3 ubiquitin ligase and stimulator of retinoic-acid-inducible gene-I. PLoS One. 2009; 4(6):e5760. 11.
  17.  Gao D*, Wang RP*, Li B, Yang Y, Zhai ZH, and Chen DY#. WDR34 is a novel TAK1-associated suppressor of the IL-1R/TLR3/TLR4-induced NF-kappaB activation pathway. Cell Mol Life Sci. 2009; 6615:2573-84.
  18. Zhang M, Wang RP, Diao FC, Lu F,Gao D, Chen D, Zhai ZH, and Shu HB#. A CXXC ring finger protein is required for DNA damage-induced p53 activation. Science in China Series C: Life Science. 2009; 52(6):528-538.
  19. Zhang M, Tian Y, Wang RP, Gao D, Zhang Y, Diao FC, Chen DY, Zhai ZH, and Shu HB#. Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3. Cell Research. 2008 Nov;18(11):1096-104.

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