[00111397]整合實驗生物學、生物信息學及計算生物學方法研究腫瘤有效治療的分子網絡
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技術詳細介紹
本課題的主要研究目標是整合實驗生物學、生物信息學以及計算生物學方法研究腫瘤有效治療的分子網絡。因此,課題組充分發揮了自身在轉錄組、蛋白質組及計算生物學方面的優勢,結合CHIP-on-Chip以及microRNA芯片技術,首先以急性早幼粒細胞白血病（acute promyelocytic leukemia,APL）為突破口,進行了系統生物學水平的調控網絡研究。從全基因組水平研究了某些異常轉錄因子在白血病發生過程中異常轉錄調控機制,通過前期課題組對動態表達譜數據的生物信息學分析,基于轉錄調控調控研究的基本思路具有共同表達調控模式的可能是受同一個或同一族轉錄因子調控這一理論,預測了與APL發生密切相關的異常轉錄因子PML/RARα下游潛在調控的靶基因。本課題首先運用高通量技術手段,結合轉錄組、蛋白質組和其它分子生物學等技術,以NB4、HL60、U937 和K562 等白血病細胞株為研究對象,系統性地分析了藥物作用下的分子網絡變化過程（Current Drug Metabolism,2008,9,1038-1048）,建立了基因表達數據庫。 1.Shi J,Yang W,Chen M,Du Y,Zhang J *and Wang K*.AMD,an Automated Motif Discovery Tool Using Stepwise Refinement of Gapped Consensuses PLoS One 2011,6:9,e24576 2.Zhang Y,Du Y Le W,Wang K,Kieffer N,Zhang J*.Redox Control of the Survival of Healthy and Diseased cells.Antioxid Redox Signal.2011,15（11）:2867-908. 3.Zhang YX,Wang C,Wang HW,Wang KK,Du YZ*,Zhang J*.Combination of Tetrandrine with cisplatin enhances cytotoxicity through growth suppression and apoptosis in ovarian cancer in vitro and in vivo.Cancer Letters 2011 （304）:21-32 4.Jiang L,Pan X,Chen Y,Wang K,Du Y*,Zhang J*.Preferential involvement of both ROS and ceramide in fenretinide-induced apoptosis of HL60 rather than NB4 and U937 cells.Biochem Biophys Res Commun.2011 Feb 11;405（2）:314-8. 5.Fang H,Du Y,Xia L,Li J,Zhang J*,Wang K*.A Topology-Preserving Selection and Clustering Approach to Multi-Dimensional Biological Data,OMICS.2011 Jul-Aug;15（7-8）:483-94. 6.Fang H,Jin W,Yang Y,Jin Y,Zhang J*,Wang K*.An organogenesis network-based comparative transcriptome analysis for understanding early human development in vivo and in vitro.BMC Syst Biol.2011 Jul 6;5:108. 7.Fang H,Yang Y,Li C,Fu S,Yang Z,Jin G,Wang K,Zhang J*,Jin Y*.Transcriptome analysis of early organogenesis in human embryos.Dev Cell.2010 Jul 20;19（1）:174-84. 8.Wang K,Wang P,Shi J,Zhu X,He M,Jia X,Yang X,Qiu F,Jin W,Qian M,Fang H,Mi J,Yang X,Xiao H,Minden M,Du Y,Chen Z,Zhang J*.PML/RARalpha targets promoter regions containing PU.1 consensus and RARE half sites in acute promyelocytic leukemia.Cancer Cell.2010 Feb 17;17（2）:186-97. 9.Wang K,Fang H,Xiao D,Zhu X,He M,Pan X,Shi J,Zhang H,Jia X,Du Y,Zhang J*.Converting redox signaling to apoptotic activities by stress-responsive regulators HSF1 and NRF2 in fenretinide treated cancer cells.PLoS One.2009 Oct 21;4（10）:e7538. 10.Fang H,Wang K,Zhang J*.Transcriptome and proteome analyses of drug interactions with natural products.Curr Drug Metab.2008 Dec;9（10）:1038-48.
