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中国科学院上海生命科学研究院专家系列学术报告(二十五)

报告一题目:癌症基因组时代的肿瘤研究与精准化治疗

报告人:郎靖瑜  上海生命科学研究院(人口健康)

报告人介绍:

1995-1999  南京大学生命学院生物科学与技术系  生物学学士

1999-2005  中科院上海药物研究所   药理学博士

2005-2011  美国得克萨斯州立大学MD 安德森癌症中心  博士后

2012  美国哈佛大学达纳法伯癌症研究所    访问学者

2012-至今  中科院上海生科院健康研究所  研究员

研究员研究方向:

1. 寻找可用于治疗乳腺癌、胃癌的新型药物作用靶点并阐明其分子机制;
2.
寻找可指示特定靶向药物受益人群的肿瘤分子标志物及其分子机制;
3.
从肿瘤干细胞角度,寻找可有效克服肿瘤复发的分子靶点及其分子机制。

主要研究成果:

1.  发现Bcl-2抗凋亡亚家族在乳腺癌干细胞生存过程中的关键作用,揭示共同抑制Bcl-2抗凋亡亚家族蛋白可以最大化杀伤乳腺癌干细胞的新策略,并成功在临床前动物试验中有效抑制了乳腺癌干细胞及紫杉醇引起的肿瘤干细胞富集现象。该研究成果发表于著名癌症杂志Cancer Cell并获得国际专利授权,美国MD安德森癌症中心即将着手进行临床I期试验。

2.  发现抗肿瘤一类新药沙尔威辛(现已进入国内II期临床试验)具有全新的抗乳腺癌转移的作用并用系统生物学方法揭示了该药物作用机理。

3.  与其他科研工作者进行了广泛的合作,发现并证实了多个癌症相关基因在体内的生物学功能和小分子抑制剂的药物作用靶点。

代表性论文

1. Huang TH, Huo L, Wang YN, Xia W, Wei Y, Chang SS, Chang WC, Fang YF, Chen CT, Lang JY, Tu C, Wang Y, Hsu MC, Kuo HP, Ko HW, Shen J, Lee HH, Lee PC, Wu Y, Chen CH, Hung MC. Epidermal Growth factor receptor potentiates MCM7-mediated DNA replication through tyrosine phosphorylation of Lyn kinase in human cancers. Cancer Cell 2013, 23(6):796-810. (Impact factor 26.9)

2. Wang Y, Ding Q, Yen CJ, Xia WY, Izzo J, Lang JY, Li CW, Miller S, Wang X, Lee DF, Hsu JL, Hsu JM, Huo L, LaBaff A, Liu DP, Huang TH, Lai CC, Tsai FJ, Chang WC, Chen CH, Wu TT, Buttar N, Wang K, Wu Y, Wang H, Ajani, J, Hung MC. The Crosstalk of mTOR/S6K1 and Hedgehog pathways. Cancer Cell. 2012 Mar 20;21(3):374-87. (impact factor 26.9)

3. Lang JY, Hsu JL, Meric-Bernstam F, Chang CJ, Wang QF, Bao Y, Yamaguchi H, Xie X, Woodward WA, Yu D, Hortobagyi GN, Hung MC. BikDD eliminates breast cancer initiating cells and synergizes with lapatinib for breast cancer treatment. Cancer Cell 2011, 20(3):341-356. (Impact factor 26.9) Leading Edge Selected: Removing breast cancer’s roots. Cell 2011, 147(2):253.

4. Ding Q, Chang CJ, Xie X, Xia W, Yang JY, Wang SC, Wang Y, Xia J, Chen L, Cai C, Li H, Yen CJ, Kuo HP, Lee DF, Lang J, Huo L, Cheng X, Chen YJ, Li CW, Jeng LB, Hsu JL, Li LY, Tan A, Curley SA, Ellis L, DuBois RA, Hung MC. APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis. J Clin Invest. 2011, 121 (11):4526-36 [Epub 2011 Oct 10]. (impact factor 14.2)

5. Banerjee A, Lang JY, Hung MC, Sengupta K, Banerjee SK, Baksi K, Banerjee DK. Unfolded protein response is required in nu/nu mice microvasculature for treating breast tumor with tunicamycin. J Biol Chem. 2011, 286(33):29127-29138 [Epub 2011 Jun 15]. (Impact factor 5.3)

6. Wei Y, Chen YH, Li LY, Lang J, Yeh SP, Shi B, Yang CC, Yang JY, Lin CY, Lai CC, Hung MC. CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells. Nat Cell Biol. 2011 13(1):87-94. (Impact factor 19.4)

报告二题目:组学时代的生物信息学

报告人:邵振  上海生命科学研究院(人口健康)

报告人介绍:

From 2013.10: Group Leader, CAS-MPG Partner Institute for Computational Biology, SIBS, CAS
2010.6-2013.9: Research Fellow of Bioinformatics and Computational Biology, Department of Pediatric Oncology, Dana Farber Cancer Institute; Division of Hematology/Oncology, Children's Hospital Boston; Harvard Medical School;
2009.4-2010.5: Research Fellow of Bioinformatics and Computational Biology, Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute and Department of Biostatistics, Harvard School of Public Health;
2003.9-2008.12: Ph. D. of Theoretical Biophysics, Institute of Theoretical Physics, Chinese Academy of Sciences, China;
1999.9-2003.7: Bachelor of Theoretical Physics, Department of Special Class for Gifted Young, University of Science and Technology of China.

主要研究方向:

1.开发针对高通量生物数据分析的统计工具和计算模型

2.基因表达调控机制研究

研究领域:

1. 开发用于分析与整合各种高通量生物数据的统计模型和计算工具
2.
与实验生物学家合作,研究组织分化与病变等过程中的动态基因调控及其潜藏机制
3.
系统生物学研究

代表成果

1. Huang J*, Liu X*, Li D*, Shao Z*, Cao H, Zhang YN, Trompouki E, Bowman TV, Zon LI, Yuan GC, Stuart H. Orkin SH#, Xu J#. Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis. Developmental Cell 2016, 36, 9-23.

2. Xu J*, Shao Z*, Li D, Xie H, Kim W, Huang J, Taylor JE, Pinello L, Glass K, Jaffe JD, Yuan GC, Orkin SH#. Developmental control of Polycomb subunit composition by GATA factors mediates a switch to non-canonical functions. Molecular Cell 2015, 57 (2), 304–316.

3. Das PP*, Shao Z*, Beyaz S, Apostolou E, O’Brien K, Atsma JM, Ljuboja D, Guo G, Kerenyi M, Woo A, Yuan GC, Onder T, Hochedlinger K, Kim J, Orkin SH#. Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cells identity. Molecular Cell 2014, 53 (1), 32-48.

4. Maroz A, Stachorski L, Emmrich S, Reinhardt K, Xu J, Shao Z, K?bler S, Dertmann T, Hitzler J, Roberts I, Vyas P, Juban G, Hennig C, Hansen G, Li Z, Orkin S, Reinhardt D, Klusmann JH. GATA1s induces hyperproliferation of eosinophil precursors in Down syndrome transient. Leukemia, 2014, 28, 1259–1270.

5. Bauer DE, Kamran SC, Lessard S, Xu J, Fujiwara Y, Lin C, Shao Z, Canver MC, Smith EC, Pinello L, Sabo PJ, Vierstra J, Voit RA, Yuan GC, Porteus MH, Stamatoyannopoulos JA, Lettre G, Orkin SH. An erythroid enhancer of BCL11A determines fetal hemoglobin level. Science, 2013, 342 (6155), 253-257.

6. Kerenyi M, Shao Z, Hsu Y, Guo G, Luc S, O’Brien K, Fujiwara Y, Peng C, Nguyen M and Orkin SH. Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation. eLife, 2013, 2:e00633.

7. Baena E, Shao Z, Linn D, Glass K, Hamblen M, Fujiwara Y, Kim J, Nguyen M, Zhang X, Godinho F, Bronson RT, Mucci L, Loda M, Yuan GC, Orkin SH and Li Z. ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients. Genes & Development, 2013, 27 (6), 683-698.

时间:2017517日下午200

地点:教四楼 B204

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