报告题目：From Disease in 3D Organoids to Clinical Trial:A New Type of Candidate for Cancer Research and Stem Cell Studies

报告人：高栋,中国科学院上海生物化学与细胞生物学研究所 研究员

时间：2019年12月27日下午：14:00‐16:00

地点：逸夫教学楼608会议室

主持人：滕春波 教授

联系人：王春生

电话：13946012096

报告人简介：

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和纪念斯隆凯特琳癌症研究所接受博士后训练，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年起担任中国科学院上海生物化学与细胞生物学研究所研究员，博士生导师。高栋实验室主要从事肿瘤类器官与肿瘤的靶向治疗研究。2014年建立了前列腺肿瘤细胞类器官培养新技术（Cell，2014），突破性地解决了长期困扰前列腺癌研究领域缺少体外模型的问题，该项工作被Yahoo新闻和Nature Methods等期刊评价为为前列腺癌治疗的革命性突破。

报告人发表的论文：

1. Tang D^#, Huang XZ^#, Wang HX^#, Li F^#, Zhu H, Li Y, He LJ, Zhang H, Pu WJ, Liu K, Zhao H, Bentzon JF, Ji Y, Nie Y,Gao D*, Zhou B*.Sca1⁺Vascular Stem Cells Contribute to Smooth Muscle for Artery Repair and Regeneration.Cell Stem Cell(accepted)

2. Mao NH,Gao D, Hu WH, Hieronymus H, Wang SQ, Lee YS, Lee C, Choi D, Gopalan A, Chen Y, Carver BS*. Aberrant expression of ERG promotes resistance to combined PI3K and AR pathway inhibition through maintenance of AR target genes.Molecular Cancer Therapeutics. 2019 Sep; 18:1577-1586

3. Wang YT^#, Zhang J^#, Ren SX^#, Sun D^#, Huang HY, Wang H, Jin YJ, Li FM, Zheng C, Yang L, Deng L, Jiang ZJ, Jiang T, Han XK, Hou SD, Guo CC, Li F,Gao D, Qin J, Gao DM, Chen LN, Lin SH, Wong KK, Li C*, Hu L*, Zhou CC*, Ji HB*. Branched-Chain Amino Acid Metabolic Reprogramming Orchestrates Drug Resistance to EGFR Tyrosine Kinase Inhibitors.Cell Reports. 2019 Jul 9;28:512-525.

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.Journal of Clinical Investigation. 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. PUCA L, Bareja R, Prandi, Shaw R, Benelli M, Karthaus W, Hess J, Sigouros M, Donoghue A, Kossai M,Gao D, Cyrta J, Sailer V, Vosoughi A, Pauli C, Churakova Y, Cheung C, Deonarine L, McNary T, Tagawa S, Nanus D, Mosquera JM, Sawyers CL, Chen Y, Inghirami G, Rao R, Grandori C, Elemento O, Sboner A, Demichelis F, Rubin M, and Beltran H*. Patient Derived Organoids to Model Rare Prostate Cancer Phenotypes.Nature Communications. 2018 Jun 19;9(1):2404.

8. 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

9. Xie Y^#, Cao Z^#, Wong EW, Guan Y, Ma W, Zhang JQ, Walczak EG, Murphy D, Ran L, Sirota I, Wang S, Shukla S,Gao D, Knott SR, Chang K, Leu J, Wongvipat J, Antonescu CR, Hannon G, Chi P*, Chen Y*. COP1-DET1-ETS axis regulates ERK transcriptome and sensitivity to MAPK inhibitors.Journal of Clinical Investigation. 2018 Apr 2;128(4):1442-1457.

10. 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.

11. Wang SQ,Gao D, Chen Y*. The potential of organoids in urological cancer research.Nature Reviews Urology. 2017 Jul;14(7):401-414

12. Li F,Gao D*. Organoid and its application in cancer research.Chinese Journal of Cell Biology. 2017 May; 39(4): 394-400

13. 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.

14. 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.

15. 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.2017 Jan 1;10(1):39-52.

16. 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.

17. 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.2016 Aug 18;11(8):e0161084.

18. 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 Feb;11(2):347-58.

19. 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,GaoD, 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 novelALKisoform in cancer.Nature. 2015 Oct 15;526(7573):453-7.

20. 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.

21. Gao Dand Chen Y*.Organoid Development in Cancer Genome Discovery.Current Opinion in Genetics and Development. 2015 Mar 18; 30:42-48. (Invited Cover Review).

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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 Mar 25;286(12):10568-80.

28. 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 Jun 1;4(6):e5760

29. 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 Aug;66(15):2573-84.

30. 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 Jun;52(6):528-38.

31. 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.