[00111397]整合实验生物学、生物信息学及计算生物学方法研究肿瘤有效治疗的分子网络

本课题的主要研究目标是整合实验生物学、生物信息学以及计算生物学方法研究肿瘤有效治疗的分子网络。因此,课题组充分发挥了自身在转录组、蛋白质组及计算生物学方面的优势,结合CHIP-on-Chip以及microRNA芯片技术,首先以急性早幼粒细胞白血病（acute promyelocytic leukemia,APL）为突破口,进行了系统生物学水平的调控网络研究。从全基因组水平研究了某些异常转录因子在白血病发生过程中异常转录调控机制,通过前期课题组对动态表达谱数据的生物信息学分析,基于转录调控调控研究的基本思路具有共同表达调控模式的可能是受同一个或同一族转录因子调控这一理论,预测了与APL发生密切相关的异常转录因子PML/RARα下游潜在调控的靶基因。本课题首先运用高通量技术手段,结合转录组、蛋白质组和其它分子生物学等技术,以NB4、HL60、U937 和K562 等白血病细胞株为研究对象,系统性地分析了药物作用下的分子网络变化过程（Current Drug Metabolism,2008,9,1038-1048）,建立了基因表达数据库。 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.