高棟(中國科學院分子細胞科學卓越創新中心研究員)

高棟(中國科學院分子細胞科學卓越創新中心研究員)

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高棟，男，中國科學院分子細胞科學卓越創新中心研究員，博士生導師。博士，先後畢業於東北林業大學、北京大學。

基本介紹

人物簡介,人物經歷,研究方向,研究工作,主要成就,代表論著,

人物簡介

高棟，男，中國科學院分子細胞科學卓越創新中心研究員，研究組長，博士生導師。

人物經歷

2005年畢業於東北林業大學，獲理學學士學位。
2011年畢業於北京大學，獲理學博士學位。
2011年8月至2016年7月先後在美國約翰霍普金斯大學和紀念斯隆凱特琳癌症研究所從事腫瘤生物學博士後研究。
2016年8月受聘於中科院上海生化與細胞所，任研究員、研究組長、博士生導師。

研究方向

類器官構建與腫瘤等疾病研究

研究工作

以正常組織類器官、腫瘤類器官、小鼠模型和臨床腫瘤標本為基礎，運用分子細胞生物學的實驗手段，研究成體幹細胞和腫瘤祖細胞的分子調控網路以及腫瘤細胞抗藥性的分子機理。目前的主要研究內容包括：
1、研究成體幹細胞和腫瘤祖細胞，尋找維持成體幹細胞多能性的主要調控基因;
2、組織器官的體外功能性構建;
3、體外重建不同時期的腫瘤類器官模型，研究腫瘤細胞可塑性與腫瘤抗藥性的分子機理;
4、建立來源於中國癌症病人的類器官模型庫，進行高通量藥物篩選，發展新的抗癌藥物。

主要成就

2024年4月10日，中國科學院分子細胞科學卓越創新中心研究員高棟與北京大學生物醫學前沿創新中心教授白凡、分子細胞卓越中心研究員陳洛南、深圳灣實驗室研究員於晨合作，系統解析了雄激素在性別差異中扮演的具體角色，對於理解性別差異性疾病的發生髮展機制以及開發性別特異的新型診療策略具有重要意義。相關研究發表於《自然》。

代表論著

  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.

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