癌生物学研究

发布者:系统管理员发布时间:2014-12-17浏览次数:3655

 

癌症是影响人类健康的重大疾病,其发病率逐年增加。肿瘤分子细胞生物学方向主要研究人类恶性肿瘤发生发展过程中的相关基因表达及其表观遗传调控机制、肿瘤细胞信号转导、肿瘤细胞结构特征与机制、肿瘤细胞表面糖链结构以及肿瘤代谢组学等问题,旨在阐明肿瘤发生发展的分子机制、推进技术应用与转化的发展,为肿瘤的早期诊断及治疗方法的探索新思路。

研究室概况

本研究室近年来研究室获得国家、省部级研究经费资助20余项,其中国家自然科学基金9项、国家863计划 3项、国家重大研究计划2项、国家重点实验室项目3项、其他省部级项目7项,获得总经费490余万元,发表SCI论文近30篇。 

承担课程

研究室教师面向本科生、硕士研究生和博士研究生承担生物化学、细胞生物学、分子生物学、免疫学、分子遗传学、分子细胞生物学、免疫学技术、肿瘤分子细胞生物学、细胞工程、基因工程、细胞工程、生物大分子结构与功能等各类课程的教学任务,并面向各类学生开放实验室,提供创新研究的技术支持。

人才培养

研究室在生物学学科招收细胞生物学,生化与分子生物学方向的理学硕士;在生物医学工程学科招收肿瘤分子细胞生物学理学博士和博士后。

国际交流:本研究方向与欧美等国际名校保持密切的合作关系,在肿瘤学领域与哈佛大学医学院、美国德州农工大学生物医学中心保持密切的合作;在糖组学领域与克利夫兰州立大学保持密切的合作。主要的合作方式有研究生共同培养、年轻教师派遣和合约教授聘请等。

主要研究方向

1. 肿瘤相关基因和蛋白的功能及其表达调控研究

研究内容涉及与肿瘤发生发展密切相关的新基因功能鉴定及表达调控分析,在基因表达调控方面主要开展肿瘤相关基因的表遗传学调控机制,包括组蛋白的甲基化、乙酰化修饰,DNA甲基化及其调控研究。同时,针对肿瘤相关miRNA的调控机制与miRNA的下游靶基因开展分析。功能研究涵盖了细胞周期与细胞增殖、细胞凋亡、DNA损伤修复、信号转导、细胞骨架动态组装及细胞与细胞外基质相互作用等分子细胞生物学问题,以及核蛋白的分子间相互作用等。目前正在研究的基因有MARVELD1c1orf109SALL4BI-1BRI-1AIF和组蛋白甲基化修饰的相互作用分子等。

2. 肿瘤细胞信号转导研究

肿瘤的生物学表型源于细胞转导机制的异常,为探讨癌变过程中细胞增殖、凋亡,粘附、运动与侵袭功能异常的信号转导机制,实验室关注了Ras家族小分子G蛋白RasRapRabRho以及Ran等信号分子在不同肿瘤和肿瘤各阶段的活化调控,以及下游信号分子通路。旨在探索细胞癌变过程中信号分子的调控机制、胞内及细胞间或细胞与细胞外基质间的信号转导分子的改变,分析产生肿瘤细胞特异性的生物学表型的分子基础。研究综合使用体外培养细胞、动物模型和临床样本分析等手段,并采用蛋白质间相互作用、蛋白活化、RNA干扰、细胞免疫荧光以及活细胞成像技术等方法对肿瘤细胞内的生理生化变化进行分析,以期阐明细胞癌变的分子机理。

3. 癌症糖组学及生物标志物研究 

以第三类生物大分子――糖为研究对象,在掌握并改进高通量N-糖基化分析的关键技术基础上,从血清、体外培养细胞和组织多个层面研究乳腺癌、肝癌、胰腺癌特异性改变的糖链分子,以及糖链结构变化与糖蛋白功能之间的关系。并与临床医学结合,建立特异性的快速、便捷、无创的血液生化检测技术,寻找新的敏感、特异的肿瘤诊断标志物,并深入探讨癌症靶向示踪的新途径、新技术。

4. 癌症代谢组学及生物标志物研究 

在建立以高通量UPLC-MS/MS为基础的代谢组学研究技术平台基础上,对不同肿瘤,开展癌症患者的血清、尿液以及临床组织样本代谢组学分析,并利用多元统计学分析,寻找癌症特征性的小分子代谢标志物,并以此为基础建立临床诊断模型,进而为相关癌症的早期诊断奠定基础。

近年发表的代表性文章:

1. Shan Wang *, Jianran Hu *, Yuanfei Yao *, Ming Shi, Lei Yue, Fang Han, Hao Zhang, Jie He, Shanshan Liu, Yu Li. MARVELD1 regulates integrin β1-mediated cell adhesion and actin organization via inhibiting its pre-mRNA processing. Int J Biochem Cell Biol. 2013; doi.org/doi:10.1016/j.biocel.2013.09.006
2. Liu X, Nie H, Zhang Y, Yao Y, Maitikabili A, Qu Y, Shi S, Chen C, Li Yu*. Cell surface-specific N-glycan profiling i n breast cancer. PLoS One. 2013; 8(8):e72704. doi: 10.1371/journal.pone.0072704.
3. He J, Zhang W, Zhou Q, Zhao T, Song Y, Chai L, Li Yu*. Low-expression of microRNA-107 inhibits cell apoptosis i n glioma by upregulation of SALL4. Int J Biochem Cell Biol. 2013; 45(9):1962-73. doi: 10.1016/j.biocel.2013.06.008.
4. Ni S, Hu J, Duan Y, Shi S, Li R, Wu H, Qu Y, Li Yu*. Down expression of LRP1B promotes cell migration via RhoA/Cdc42 pathway and actin cytoskeleton remodeling i n renal cell cancer. Cancer Sci. 2013; 104(7):817-25. doi: 10.1111/cas.12157.
5. Ling S, Birnbaum Y, Nanhwan MK, Thomas B, Bajaj M, Li Y, Li Y, Ye Y. Dickkopf-1 (DKK1) phosphatase and tensin homolog on chromosome 10 (PTEN) crosstalk via microRNA interference i n the diabetic heart. Basic Res Cardiol. 2013; 108(3):352. doi: 10.1007/s00395-013-0352-2.
6. Qinghua Jiang, Guohua Wang, Shuilin Jin, Yu Li, Yadong Wang. Predicting human microRNA-disease associations based on support vector machine. Int. J. Data Mining and Bioinformatics 2013; 8(3), 282-293.
7. Wang haochang, Li Yu. Co-decision Matrix Framework for Name Entity Recognition i n Biomedical Text. International Journal of Data Mining and Bioinformatics. 2013. Accepted.
8. Wang haochang, Li Yu. Transductive Support Vector Machines and Active Learning for Extracting Protein-Protein Interactions. Journal of Investigative Medicine. 2013; 61(4)
9. Shan-shan Liu, Hong-xia Zheng, Hua-dong Jiang, Jie He, Yang Yu, You-peng Qu, Lei Yue, Yao Zhang, Yu Li. Identification and characterization of a novel gene, c1orf109, encoding a CK2 substrate that is involved i n cancer cell proliferation. Journal of biomedical science 2012; 19:49. doi: 10.1186/1423-0127-19-49.
10. Huan Nie, Yu Li and Xue-Long Sun. Recent Advances i n Sialic Acid-Focused Glycomics. Journal of Proteomics. 2012; 75(11):3098-112. doi: 10.1016/j.jprot.2012.03.050.
11. Satya Nandana Narla, Huan Nie, Yu Li, Xue-Long Sun. Recent Advances i n the Synthesis and Biomedical Applications of Chain-End Functionalized Glycopolymers. Journal of Carbohydrate Chemistry, 2012; 31(2):67-92
12. Youtao Yu*, Yubao Zhang*, Jianran Hu, Hao Zhang , Shan Wang, Fang Han, Lei Yue, Youpeng Qu, Yao Zhang, Hongjian Liang, Huan Nie, Yu Li. MARVELD1 inhibited cell proliferation and enhance chemosensitivity via increasing expression of p53 and p16 i n hepatocellular carcinoma. Cancer Science. 2012;103(4):716-22. doi: 10.1111/j.1349-7006.2012.02220.x.
13. Wenying Mu, Shanguang Chen, Fengyuan Zhuang, Yinghui Li, Yu Li. Quantification of the distribution of blood flow pressure with postures. J Biomedical Science and Engineering( JbiSE), 2012; 5, 113-119 doi:10.4236/jbise.2012.53015
14. Hong-xia Zheng, Shan-shan Liu, Wei-ming Tian, Hong-ji Yan, Yao Zhang, Yu Li. A three-dimensional i n vitro culture model for primary neonatal rat ventricular myocytes. Current applied physics, 2012; 12(3):826-833.
15. Zheng Hongxia*, Tian Weiming*, Yue Lei, Zhang Yao, Yu Li. Rotary culture promotes the proliferation of MCF-7 cells encapsulated i n three-dimensional collagen-alginate hydrogels via activation of ERK1/2-MAPK pathway, Biomedical materials, 2012; 7(1):015003.
16. Zheng Hongxia, Tian Weiming, Yan Hongji, Jiang Huadong, Liu Shan-shan, Yue Lei, Zhang Yao, Han Fengtong, Yu Li. Expression of estrogen receptor αi n human breast cancer cells regulated mitochondrial oxidative stress under simulated microgravity. Advances i n Space Research, 2012; 49(10):1432-1440.
17. Liu Shanshan, Chen Xiangmei, Zheng Hongxia, Shi Shuliang, Yu Li. Knockdown of Rab5a expression decreases cancer cell motility and invasion through integrin-mediated signaling pathway. J Biomed Sci. 2011; 18:58.
18. Bai, X. P. *; Zheng, H. X. *; Fang, R.; Wang, T. R.; Hou, X. L.; Li, Y.; Chen, X. B.; Tian, W. M., Fabrication of engineered heart tissue grafts from alginate/collagen barium composite microbeads. Biomedical Materials. 2011; 6(4):045002.
19. Shan Wang, Jianran Hu, Fang Han, Jie He, Shanshan Liu, Lei Yue, Yao Zhang, Yu Li. Nuclear protein MARVELD1 inhibits tumor cell adhesion and cell motility via affecting pre-mRNA processing of focal adhesion genes. The 2011 American Society for Cell Biology Annual Meeting.
20. Ding N*, Nie H*, Sun X, Sun W, Qu Y, Liu X, Yao Y, Liang X, Chen CC, Yu Li. Human Serum N-Glycan Profiles Are Age and Sex Dependent. Age Ageing. 2011; 40(5):568-75.
21. Fanli Zeng, Yanyan Tian, Shuliang Shi, Qiong Wu, Lei Yue, Yao Zhang, Yu Li. Identification of mouse MARVELD1 as a candidate microtubule-associated protein that inhibites cell-cycle progression and migration. Molecules and Cells. 2011 31(3):267-74.
22. 梁雪, 聂桓, 李钰. 胰腺癌早期诊断肿瘤标志物的研究进展. 实用肿瘤杂志,2011; 4:422-426
23. 沈春雯, 高忠江, 施树良. 小分子量G蛋白Rap2信号途径的生物学功能. 中国细胞生物学学报2010; 32,1:17-23
24. Shan Wang, Yu Li, Fang Han, Jianran Hu, Lei Yue, Youtao Yu, Yubao Zhang, Jie He, Hongxia Zheng, Shuliang Shi, Xiaowei Fu, Hongjin Wu. Identification and characterization of MARVELD1, a novel nuclear protein that is downregulated i n multiple cancers and silenced by DNA methylation. Cancer Letters. 2009; 282:77-86.
25. Huan Nie,Ding ning,Sun wei,Yu Youtao ,Yu Yan,Zhang Yubao ,Qu Youpeng, Wang Shan, Li Yu. N-Glycomic Changes i n Serum for the Discovery of Potential Biomarkers of Breast Cancer. 21st IUBMB and 12th FAOBMB International Congress of Biochemistry and Molecular Biology
26. 王山, 肖晟, 赫杰, 韩放, 李钰. 核蛋白MARVELD1与核质转运受体蛋白Importin β1相互作用的鉴定.《中国生物化学与分子生物学报》 2009; 25(08),735-739
27. 李若, 田艳艳, 高勇, 王山, 聂桓, 李钰. 应用RNAi技术沉默大转录本基因LRP1B.遗传, 2009; 31(01), 36-42
28. 向穷,施树良,李钰. 小分子G蛋白R-Ras介导的细胞信号转导通路及其生物学功能 生物技术通讯 2009; 20(5), 695-698
29. 向穷, 施树良, 李钰. 常用统计软件在生物统计中的应用比较  现代生物医学进展 2009; 9(9),1775-1777
30. 杨宗义, 田艳艳, 李钰, 韩放. 小鼠mP24基因的原核表达及多抗制备,现代生物医学进展2009; 13,2428-2431
31. 高忠江, 施树良, 李钰. SPSS方差分析在生物统计的应用 现代生物医学进展 2008; 8(11), 2116-2120
32. Hongjin Wu, Mengya Gao, Shan Wang, Yu Li. Transcriptional regulation analysis of a novel human lung adenocarcinoma metastasis-regulated gene (MARVELD1). Proceedings of the International Symposium on Biological and Physiological Engineering/The 22nd SICE Symposium on Biological and Physiological Engineering. 2008. P8-2:322-326.
33. Jie He, Yong Gao, Meihong Lü, Yu Li. Localization Analysis of UTRN Protein i n Human Lung Adenocarcinoma Cells. Proceedings of the International Symposium on Biological and Physiological Engineering, 2008, 327-329.
34. Li Yu, Jianmin Huang, Yan-Ling Zhao, Ji He, Wei Wang, Kay E. Davies, Vânia Nosé, and Sheng Xiao. UTRN on chromosome 6q24 is mutated i n multiple tumors. Oncogene 2007;26: 6220-6228.
35. Fangli Liu, Yu Li, Yang Yu, Songbin Fu and Pu Li. Cloning of Novel Tumor Metastasis-Related Genes from the Highly Metastatic Human Lung Adenocarcinoma Cell Line Anip973. Journal of Genetics and Genomics. 2007; 34(3): 189-195
36. Li Yu, Qing Chang, Brian P. Rubin, Christopher D.M. Fletcher, Thomas W. Morgan, Steven J. Mentzer, David J. Sugarbaker, Jonathan A. Fletcher, and Sheng Xiao. Insulin Receptor Activation i n Solitary Fibrous Tumors. J. of Pathology. 2007; 211:550-554.