首页 > 科学研究 > 基因调控课题组

> 课题组简介

  本课题组应用系统生物学的理念和方法,围绕白血病发病和治疗的调控机制这一核心问题,从实验生物学、计算生物学、功能基因组学等多学科开展研究。本课题组在基础研究、临床转化和技术手段等多方面取得了一系列原创性成果:①从广度上,应用高通量、多组学的研究理念揭示白血病受累的融合蛋白全基因组水平的靶基因及转录调控网络;②从深度上,应用分子、细胞和动物实验详细解析融合蛋白调控下游多个关键基因(PSMBs、CDKN2D、CDKN2C、HCK、PU.1、TF、CTSG等)以及非编码RNA(HOTAIRM1等)的机制,揭示其在白血病发生中的功能;③从临床应用角度,揭示多种白血病有效治疗方案的调控机制及网络,并发现小分子化合物Fenretinide特异性诱导AML白血病干细胞凋亡的效能(获中国和美国专利授权各一项);④开发一系列具有自主知识产权的高通量数据分析方法(获软件著作权授权三项)。研究成果在Cancer Cell、Blood、PNAS、Oncogene等国际主流刊物发表论文数十篇,获得国家863计划、973计划、国家自然科学基金重点以及面上等多个项目资助,并获得了包括教育部自然科学奖一等奖、上海市科学技术奖一等奖、中华医学科技奖二等奖、上海医学科技奖一等奖在内的多项学术奖励。

> 课题组长:王侃侃


> 代表性论文

1. Li Y, Wang H, Wang X, Jin W, Tan Y, Fang H, Chen S, Chen Z, Wang K. Genome-wide studies identify a novel interplay between AML1 and AML1/ETO in t(8;21) acute myeloid leukemia. Blood. 2016;127(2):233-242.
2. Wei S, Zhao M, Wang X, Li Y, Wang K. PU.1 controls the expression of long noncoding RNA HOTAIRM1 during granulocytic differentiation. Journal of Hematology & Oncology. 2016;9:44.
3. Wang X, Tan Y, Li Y, Li J, Jin W, Wang K. Repression of CDKN2C caused by PML/RARα binding promotes the proliferation and differentiation block in acute promyelocytic leukemia. Frontiers of Medicine. 2016;10(4):420-9.
4. Wei S, Wang K. Long noncoding RNAs: pivotal regulators in acute myeloid leukemia. Experimental Hematology & Oncology. 2016;5:30.
5. Yang X, Wang P, Liu J, Zhang H, Xi W, Jia X, Wang K. Coordinated regulation of the immunoproteasome subunits by PML/RARα and PU.1 in acute promyelocytic leukemia. Oncogene. 2014;33(21):2700-8.
6. Wang Y, Jin W, Jia X, Luo R, Tan Y, Zhu X, Yang X, Wang X, Wang K. Transcriptional repression of CDKN2D by PML/RARα contributes to the altered proliferation and differentiation block of acute promyelocytic leukemia cells. Cell Death and Disease. 2014; 5, e1431.
7. Zhang H, Fang H, Wang K. Reactive oxygen species in eradicating acute myeloid leukemic stem cells. Stem cell investigation. 2014; 1:13.
8. Zhang H, Mi J, Fang H, Wang Z, Wang C, Wu L, Zhang B, Yang W, Wang H, Minden M, Li J, Xi X, Chen S, Zhang J, Chen Z and Wang K. Preferential eradication of acute myelogenous leukemia stem cells by fenretinide. Proc Natl AcadSci USA. 2013;110(14):5606-11.
9. Luo R, Ye L, Tao C, Wang K. Simulation of E. coli gene regulation including overlapping cell cycles, growth, division, time delays and noise. PLoS One. 2013;8(4):e62380.
10. Jin W, Wu K, Li Y, Yang W, Zou B, Zhang F, Zhang J, Wang K. AML1-ETO targets and suppresses cathepsin G, a serine protease, which is able to degrade AML1-ETO in t(8;21) acute myeloid leukemia. Oncogene. 2013;32(15): 1978-87.
11. Qian M, Jin W, Zhu X, Jia X, Yang X, Du Y, Wang K* and Zhang J. Structurally differentiated cis-elements that interact with PU.1 are functionally distinguishable in acute promyelocytic leukemia. Journal of Hematology & Oncology. 2013;6:25. (*co-corresponding author)
12. Zhu X, Zhang H, Qian M, Zhao X, Yang W, Wang P, Zhang J and Wang K. The significance of low PU.1 expression in patients with acute promyelocytic leukemia. Journal of Hematology & Oncology. 2012;5:22.
13. Zou D, Yang X, Wang P, Zhu X, Yang W, Jia X, Zhang J and Wang K. Regulation of the hematopoietic cell kinase gene by PML/RARα and PU.1 in acute promyelocytic leukemia. Leukemia Res. 2012;36:219-223.
14. 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.
15. 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;15(7-8): 483-94.
16. Fang H, Jin W, Yang Y, Jin Y, Zhang J and Wang K. An organogenesis network-based comparative transcriptome analysis for understanding early human development in vivo and in vitro. BMC Systems Biology. 2011;5:108.
17. 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, and Zhang J. PML/RAR targets promoter regions containing PU.1 consensus and RARE half sites in acute promyelocytic leukemia. Cancer Cell. 2010;17(2):186-197.
18. Yan J, Wang K#, Dong L, Liu H, Chen W, Xi W, Ding Q, Kieffer N, Caen J, Chen S, Chen Z and Xi X. PML/RARα fusion protein transactivates the tissue factor promoter through a GAGC-containing element without direct DNA association. Proc Natl Acad Sci USA. 2010;107(8):3716-21. (# co-first author)