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个人简介

余科 ( Ker Yu),女,研究员、博士生导师。1988年毕业于芝加哥大学分子遗传及细胞生物学博士。1990-1992年先后完成麻省理工学院、康乃尔大学医学院博士后研究。1992-2010年历任诺华药业公司副研究员,惠氏药业公司资深主任研究员,桑迪亚生物技术公司副总经理,2011年3月引进复旦大学药学院。自1992年起从事肿瘤分子机理、新药靶点发掘和验证研究,主持惠氏、诺华药业一类新药创制专题12项。 长期致力于 mTOR/PI3K/AKT 相关信号通路的疾病研究和新药创制,发表相关论文、专著、专利等70余篇,对 Torisel/CCI-779、PKI-587、MTI-178 等项目开发及临床研究作出了重要贡献。2008年为表彰 mTOR 抑制剂 Torisel 的研发成果荣获美国化学学会工业创新最高等奖“Heroes of Chemistry”,2004-2009年四次荣获惠氏药业新药研发项目成就奖,被选为股东年报专题介绍。回国后高度关注肿瘤靶向治疗药物研发的协同创新,主持、参与主持1.1类新药研发项目CM082 (IND 2011)、CM-118 (IND 2014)、SCC-31 (IND 2015)。 教育经历 1982/10-1988/03 芝加哥大学 分子遗传和细胞生物学 博士 1982/01-1982/09 复旦大学 遗传所 研究生 1978/03-1982/01 上海师范大学 生物学 学士 工作经历 2011/03- 现在 复旦大学药学院 研究员 2010/04-2010/12 桑迪亚生物技术公司 副总经理 1996/07-2010/03 惠氏药业公司 主任研究员-Ⅲ 1992/09-1996/06 诺华药业公司 副研究员 1991/04-1992/08 康奈尔大学医学院 博士后 1988/03-1990/10 麻省理工学院 博士后

研究领域

有关癌症及其它疾病的靶向治疗研究并立足于创新药物开发,靶点包括信号通路激酶,细胞表面受体,肿瘤代谢调控机制等,策略为小分子化合物和创新单抗治疗药物。 基于肿瘤相关信号通路新分子位点的发现和验证,着重于疾病模型中的功能测定分析,药物新靶点的探索性研究。

近期论文

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Toral-Barza L, Zhang WG, Huang X, McDonald LA, Salaski EJ, Barbieri LR, Ding WD, Krishnamurthy G, Hu YB, Lucas J, Bernan VS, Cai P, Levin JI, Mansour TS, Gibbons JJ, Abraham RT, Yu K. Discovery of lactoquinomycin and related pyranonaphthoquinones as potent and allosteric inhibitors of AKT/PKB: mechanistic involvement of AKT catalytic activation loop cysteines. Mol Cancer Ther. 2007; 6:3028-38 He H, Janso JE, Yang HY, Bernan VS, Lin SL, Yu K. Culicinin D, an Antitumor Peptaibol Produced by the Fungus Culicinomyces clavisporus, Strain LL-12I252. J Nat Prod. 2007; 69(5):736-41 Shor B, Zhang WG, Toral-Barza L, Lucas J, Abraham RT, Gibbons J, Yu K. A new pharmacological action of CCI-779 involves FKBP12-independent inhibition of mTOR kinase activity and profound repression of global protein synthesis. Cancer Res. 2008; 68:2934-43 Yu K, Toral-Barza L, Shi C, Zhang WG, Lucas J, Shor B, Kim J, Verheijen J, Curran K, Malwitz DJ, Cole DC, Ellingboe J, Ayral-Kaloustian S, Mansour TS, Gibbons JJ, Abraham RT, Nowak P, Zask A. Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin. Cancer Res. 2009; 69:6232-40 Zask A, Verheijen JC, Curran K, Kaplan J, Richard DJ, Nowak P, Malwitz DJ, Brooijmans N, Bard J, Svenson K, Lucas J, Toral-Barza L, Zhang WG, Hollander I, Gibbons JJ, Abraham RT, Ayral-Kaloustian S, Mansour TS, Yu K. ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines. J Med Chem. 2009; 52:5013-16 Nowak P, Cole DC, Brooijmans N, Bursavich MG, Curran KJ, Ellingboe JW, Gibbons JJ, Hollander I, Hu Y, Kaplan J, Malwitz DJ, Toral-Barza L, Verheijen JC, Zask A, Zhang WG, Yu K. Discovery of Potent and Selective Inhibitors of the Mammalian Target of Rapamycin (mTOR) Kinase. J Med Chem. 2009; 52:7081-89 Gibbons JJ, Abraham RT, Yu K. Mammalian Target of Rapamycin: Discovery of Rapamycin Reveals a Signaling Pathway Important for Normal and Cancer Cell Growth. Seminars in Oncology 2009; 36:3-17 Shor B, Gibbons JJ, Abraham RT, Yu K. Targeting mTOR globally in cancer: Thinking beyond rapamycin. Cell Cycle 2009; 8:3831-37 Yu K, Shi C, Toral-Barza L, Lucas J, Shor B, Kim JE, Zhang WG, Mahoney R, Gaydos C, Tardio L, Kim SK, Conant R, Curran K, Kaplan J, Verheijen J, Ayral-Kaloustian S, Mansour TS, Abraham RT, Zask A, and Gibbons JJ. Beyond rapalog therapy: preclinical pharmacology and antitumor activity of WYE-125132, an ATP-competitive and specific inhibitor of mTORC1 and mTORC2. Cancer Res. 2010; 70:621-31 Zask A, Kaplan J, Verheijen JC, Richard DJ, Curran K, Brooijmans N, Bennett EM, Toral-Barza L, Hollander I, Ayral-Kaloustian S, Yu K. Morpholine derivatives greatly enhance the selectivity of mammalian target of rapamycin (mTOR) inhibitors. J Med Chem. 2009; 52:7942-45 Ayral-Kaloustian S, Gu J, Lucas J, Cinque M, Gaydos C, Zask A, Chaudhary I, Wang J, Di L, Young M, Ruppen M, Mansour TS, Gibbons JJ, Yu K. Hybrid Inhibitors of Phosphatidylinositol-3-Kinase (PI3K) and the Mammalian Target of Rapamycin (mTOR): Design, Synthesis, and Superior Antitumor Activity of Novel Wortmannin-Rapamycin Conjugates. J Med Chem. 2010; 53:452-59 Shor B, Wu J, Shakey Q, Toral-Barza L, Follettie M, Yu K. Requirement of mTOR kinase for the regulation of Maf1 phosphorylation and control of RNA polymerase III-dependent transcription in cancer cells. J Biol Chem. 2010; 285:15380-92 Eng C, Yu K, Lucas J, White E, Abraham RT. Ammonia derived from glutaminolysis is a diffusible regulator of autophagy. Sci Signal. 2010; 3(119):ra31 Yu K and Toral-Barza L. Biochemical and pharmacological inhibition of mTOR by rapamycin and an ATP-competitive mTOR inhibitor. Methods Mol Biol. 2012;821:15-28 Gopalsamy A, Bennett EM, Shi M, Zhang WG, Bard J, Yu K. Identification of pyrimidine derivatives as hSMG-1 inhibitors. Bioorg Med Chem Lett. 2012; 22:6636-41 Meng L, Shu M, Chen Y, Yang D, He Q, Zhao H, Feng Z, Liang C, Yu K. A novel lead compound CM-118: antitumor activity and new insight into the molecular mechanism and combination therapy strategy in c-Met- and ALK-dependent cancers. Cancer Biol Ther. 2014; 15:721-34 Chen Y, Qian J, He Q, Zhao H, Toral-Barza L, Shi C, Zhang X, Wu J, Yu K. mTOR complex-2 stimulates acetyl-CoA and de novo lipogenesis through ATP citrate lyase in HER2/PIK3CA-hyperactive breast cancer. Oncotarget 2016; 7:25224-40 Qian J, Chen Y, Meng T, Ma L, Meng L, Wang X, Yu T, Zask A, Shen J, Yu K. Molecular regulation of apoptotic machinery and lipid metabolism by mTORC1/mTORC2 dual inhibitors in preclinical models of HER2+/PIK3CAmut breast cancer. Oncotarget 2016; 7:67071-86 Zhang X, Li Q, Zhao H, Ma L, Meng T, Qian J, Jin R, Shen J, Yu K. Pathological expression of tissue factor confers promising antitumor response to a novel therapeutic antibody SC1 in triple negative breast cancer and pancreatic adenocarcinoma. Oncotarget 2017; 8:59086-102 Li Q, Zhao H, Zhang X, Lang H, Yu K. Novel Smoothened inhibitors for therapeutic targeting of na?ve and drug-resistant hedgehog pathway-driven cancers. Acta Pharmacologica Sinica 2018 May 18. doi: 10.1038/s41401-018-0019-5. [Epub ahead of print]

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