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唐玉杰

腫瘤的表觀遺傳分子診斷與藥物治療研究組

電話：021-63846590-776925

郵箱：[email protected].

本課題組與上海新華醫(yī)院小兒神經(jīng)外科、上海兒童醫(yī)院普外科,、上海仁濟醫(yī)院肝臟外科,、上海第一人民醫(yī)院骨科等多家附屬醫(yī)院的兒童腫瘤相關(guān)科室進行聯(lián)合攻關(guān)，聯(lián)合應(yīng)用計算生物學(xué),、基因組學(xué),、表觀遺傳學(xué)和干細胞生物學(xué)等多種研究方法和系統(tǒng)生物學(xué)研究策略，針對包括兒童腦瘤,、神經(jīng)母細胞瘤,、肝母細胞瘤和尤文肉瘤等在內(nèi)的多類兒童實體瘤開展基礎(chǔ)醫(yī)學(xué)研究。近年來已經(jīng)在發(fā)病率最高的兩類惡性兒童腦瘤髓母細胞瘤與兒童腦干膠質(zhì)瘤DIPG的的表觀遺傳致病分子機制與靶向診療策略方向取得系列創(chuàng)新性研究成果,，發(fā)現(xiàn)BET抑制分子,、CDK7抑制分子可有效治療SHH亞型髓母細胞瘤并能顯著克服目前臨床靶向藥物的抗藥性；解析H3-K27M組蛋白突變介導(dǎo)的兒童腦干膠質(zhì)瘤DIPG表觀遺傳發(fā)病新機制,，并發(fā)現(xiàn)HDAC抑制分子,、BET抑制分子和CDK7抑制分子等多類表觀遺傳靶向藥物在預(yù)臨床腫瘤模型中能夠有效治療DIPG等，以第一/共同第一作者或通訊/共同通訊作者在Nature Medicine,、Cancer Cell和PNAS等刊物發(fā)表多篇研究論文,，為拓展惡性兒童腦瘤的表觀遺傳致病機制與靶向治療研究方向做出了重要貢獻，其中一項研究直接推動了獲FDA批準的HDAC抑制分子藥物panobinostat開展針對DIPG的人體臨床試驗,，成為根據(jù)預(yù)臨床試驗結(jié)果開展DIPG靶向藥物臨床試驗的重大突破,。

唐玉杰，國家海外高層次青年人才,，上海市青年“科技啟明星”?，F(xiàn)任上海交通大學(xué)醫(yī)學(xué)院基礎(chǔ)醫(yī)學(xué)院病理生理學(xué)系課題組長，研究員/博導(dǎo),。2003年本科畢業(yè)于中國科技大學(xué),，2009年博士畢業(yè)于中科院上海生科院生化細胞所，2010-2015年期間在美國斯坦福大學(xué)進行博士后深造,。近年來重點關(guān)注兒童實體瘤的表觀遺傳致病機制與靶向診療,，以第一/共同第一作者或通訊/共同通訊作者在Nature Medicine、Cancer Cell和PNAS等刊物發(fā)表多篇研究論文,。

1. Jiajia Wang#, Yi Sui#, Qifeng Li#, Yang Zhao, Xiaoshu Dong, Jian Yang, Zhuangzhuang Liang, Yipeng Han, Yujie Tang*, Jie Ma*, Effective inhibition of MYC-amplified group 3 medulloblastoma by FACT-targeted curaxin drug CBL0137, Cell Death Dis, 2020 Dec 2;11(12):1029.

2. Fang Liu#, Wenyan Jiang#, Yi Sui#, Wei Meng, Linjun Hou, Tiantian Li, Meng Li, Lei Zhang, Jialin Mo, Jiajia Wang, Yang Zhao, Liye Zhang, Jie Ma*, and Yujie Tang*, CDK7 inhibition suppresses aberrant hedgehog pathway and overcomes resistance to smoothened antagonists, Proc Natl Acad Sci U S A. 2019 Jun 25;116(26):12986-12995.

3. Ping Lu#, Jing Geng#, Lei Zhang#, Yu Wang, Ningning Niu, Yuan Fang, Fang Liu, Juanjuan Shi, Zhi-Gang Zhang, Yong-Wei Sun, Li-Wei Wang*, Yujie Tang*, Jing Xue*, THZ1 reveals CDK7-dependent transcriptional addictions in pancreatic cancer, Oncogene. 2019 May;38(20):3932-3945.

4. Meng W#, Wang B#, Mao W#, Wang J, Zhao Y, Li Q, Zhang C, Tang Y*, Ma J*. Enhanced efficacy of histone deacetylase inhibitor combined with bromodomain inhibitor in glioblastoma. J Exp Clin Cancer Res. 2018 Oct 1;37(1):241.

5. Meng W#, Wang J#, Wang B#, Liu F, Li M, Zhao Y, Zhang C, Li Q, Chen J, Zhang L, Tang Y*, Ma J*. CDK7 inhibition is a novel therapeutic strategy against GBM both in vitro and in vivo. Cancer Manag Res. 2018 Nov 15;10:5747-5758.

6. Nagaraja S, Vitanza NA, Woo PJ, Taylor KR, Liu F, Zhang L, Li M, Meng W, Ponnuswami A, Sun W, Ma J, Hulleman E, Swigut T, Wysocka J, Tang YJ*, Monje M*. Transcriptional Dependencies in Diffuse Intrinsic Pontine Glioma. Cancer Cell.2017;31(5):635-652.e6.

7. Jones C, Karajannis MA, Jones DTW, Kieran MW, Monje M, Baker SJ, Becher OJ,Cho YJ, Gupta N, Hawkins C, Hargrave D, Haas-Kogan DA, Jabado N, Li XN, MuellerS, Nicolaides T, Packer RJ, Persson AI, Phillips JJ, Simonds EF, Stafford JM,Tang YJ, Pfister SM, Weiss WA. Pediatric high-grade glioma: biologically andclinically in need of new thinking. Neuro Oncol. 2017;19(2):153-161.

8. Grasso CS#, Tang YJ#, Truffaux N#, Berlow NE, Liu L, Debily MA, Quist MJ, DavisLE, Huang EC, Woo PJ, Ponnuswami A, Chen S, Johung TB, Sun W, Kogiso M, Du Y, Qi L, Huang Y, Hütt-Cabezas M, Warren KE, Le Dret L, Meltzer PS, Mao H, Quezado M,van Vuurden DG, Abraham J, Fouladi M, Svalina MN, Wang N, Hawkins C, Nazarian J,Alonso MM, Raabe EH, Hulleman E, Spellman PT, Li XN, Keller C, Pal R, Grill J, Monje M. Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat Med. 2015 Jun;21(6):555-9.

9. Tang YJ, Gholamin S, Schubert S, Willardson MI, Lee A, Bandopadhayay P,Bergthold G, Masoud S, Nguyen B, Vue N, Balansay B, Yu F, Oh S, Woo P, Chen S,Ponnuswami A, Monje M, Atwood SX, Whitson RJ, Mitra S, Cheshier SH, Qi J,Beroukhim R, Tang JY, Wechsler-Reya R, Oro AE, Link BA, Bradner JE, Cho YJ.Epigenetic targeting of Hedgehog pathway transcriptional output through BETbromodomain inhibition. Nat Med. 2014;20(7):732-40.

10. Bender S^#, Tang YJ^#, Lindroth AM^#, Hovestadt V, Jones DT, Kool M, Zapatka M,Northcott PA, Sturm D, Wang W, Radlwimmer B, Højfeldt JW, Truffaux N, Castel D,Schubert S, Ryzhova M, Seker-Cin H, Gronych J, Johann PD, Stark S, Meyer J, MildeT, Schuhmann M, Ebinger M, Monoranu CM, Ponnuswami A, Chen S, Jones C, Witt O,Collins VP, von Deimling A, Jabado N, Puget S, Grill J, Helin K, Korshunov A,Lichter P, Monje M, Plass C, Cho YJ, Pfister SM. Reduced H3K27me3 and DNAhypomethylation are major drivers of gene expression in K27M mutant pediatrichigh-grade gliomas. Cancer Cell. 2013;24(5):660-72.

助研：張蕾,，莫嘉林

實驗員：蔣文艷

博士研究生：李孟,，隋怡，韓雨潔

碩士研究生：李瑞,，翁文筠

已畢業(yè)學(xué)生：李添添（碩士）