Zhang Yu-哈尔滨医科大学遗传学研究室

Yu Zhang

Tel (O)

010-87788425

E-mail

zhangyu909@126.com

Address (office)

State Key Laboratory of Molecular Oncology,

Cancer Hospital (Institute), Peking Union Medical College

Old Ward building 4109

17 Panjiayuan Nanli, Chaoyang District

Beijing 100021, China

Education

2000.9-2003.7	Harbin Medical University, P.R. China
	PhD, Medical Genetics and Cell Biology
1995.9-1998.7	Harbin Normal University, P.R. China
	MS, Biochemistry and Molecular biology
1991.9-1995.7	Harbin Normal University, P.R. China
	BS, Biology

Study abroad

2001.12- 2002.7

Visiting scholar

Laboratory of Cancer Genetics

Department of Clinical Oncology

Queen Mary Hospital, HK University, HK

1997.10-1998.4

Visiting scholar

Plant biotechnology institute (PBI)

National Research Council (NRC), Canada

Employment

2008.7-present	Associate Professor State Key Laboratory of Molecular Oncology Cancer Hospital (Institute), PUMC, Beijing, China
2006.1-2008.7	Lecturer State Key Laboratory of Molecular Oncology Cancer Hospital (Institute), PUMC, Beijing, China
2003.12-2005.12	Postdoctoral Fellow State Key Laboratory of Molecular Oncology Cancer Hospital (Institute), PUMC, Beijing, China
1998.9-2003.11	Research assistant and Lecturer Laboratory of Medical Genetics and Cell Biology Harbin Medical University

Members of professional societies

² The Genetics Society of China (GSC), Youth committee member

² Cancer Etiology Branch of Chinese Anti-Cancer Association, Youth committee member

² Chinese Society for Cell Biology (CSCB)

Research Interest and current projects

Our research group has been working on pathogenesis of human cancers. The overall research interest of our lab is to understand the function and related molecular mechanism of tumor related genes in human malignant tumors, such as esophageal and colorectal cancers. Meanwhile, we also work on identifying biomarkers and discovering novel therapeutic targets. In particular, we are trying to develop the target therapy and combination therapy strategy in ESCC and CRC treatment.

Recent years, we use the cell and animal models to investigate the function and mechanism of polo-like kinase 1 (PLK1), a member of the highly conserved serine/threonine protein kinase family. PLK1 is a key regulator of cell division and is also a central player in maintaining genome stability during DNA replication and in modulating the DNA damage response. PLK1 is frequently up-regulated in the vast majority of human tumors but not in healthy, non-dividing cells.

Our group found that overexpression of PLK1 was an independent prognostic factor in esophageal squamous cell carcinoma (ESCC). Functional study revealed that overexpression of PLK1 inhibits apoptosis via enhancement of survivin level in ESCC (IJC.2009,124(3):578-88). Subsequently, we found that PLK1 is transcriptionally activated by NF-kB during cell detachment and enhances anoikis resistance through inhibiting beta-catenin degradation in esophageal cancer (Clin Cancer Res. 2011;17: 4285-95). Most recently, we demonstrated that reciprocal activation between PLK1 and Stat3 contributes to survival and proliferation of ESCC cells (Gastroenterology. 2012;142(3):521-30).

At present, we are further exploring the underlying mechanisms of PLK1 mediated the malignant proliferation of ESCC and CRC. At the same time, we are investigating the functional role of aberrant PLK1 expression in esophageal and colorectal tumorigenesis with established CRC and ESCC mouse model, and PLK1 knockout mice.

Publications

First author articles (last five years)

1. Zhang Y, Du XL, Wang CJ, Lin DC, Ruan X, Feng YB, Huo YQ, Peng H, Cui JL, Zhang TT, Wang YQ, Zhang H, Zhan QM, Wang MR. Reciprocal Activation Between PLK1 and Stat3 Contributes to Survival and Proliferation of Esophageal Cancer Cells.Gastroenterology. 2012;142(3):521-30. [Li G, Guo G: 2012. F1000.com /14217958#eval15732064]

2. Zhang Y, Feng YB, Shen XM, Chen BS, Du XL, Luo ML, Cai Y, Han YL, Xu X, Zhan QM, Wang MR. Exogenous expression of Esophagin/SPRR3 attenuates the tumorigenicity of esophageal squamous cell carcinoma cells via promoting apoptosis. Int J Cancer. 2008;122(2):260-6.[Fast tract]

3. Zhang Y, Huang X, Qi J, Yan C, Xu X, Han Y, Wang M. Correlation of genomic and expression alterations of AS3 with esophageal squamous cell carcinoma. J Genet Genomics. 2008;35(5):267-71.

Corresponding author articles * (last two years)

1. Zhou HT, Shi ZZ, Zhou ZX, Jiang YY, Hao JJ, Zhang TT, Shi F, Xu X, Wang MR and Zhang Y*. Genomic changes in rectal adenocarcinoma associated with liver metastasis. Cancer Biomarkers. 2013,13:281-288

2. Shi ZZ, Zhang YM, Shang L, Hao JJ, Zhang TT, Wang BS, Liang JW, Chen X, Zhang Y, Wang GQ, Wang MR*, Zhang Y*. Genomic profiling of rectal adenoma and carcinoma by array-based comparative genomic hybridization. BMC Medical Genomics. 2012;5(1):52.

3. Liang JW，Shi ZZ, Wang MR, Zhang TT, Hao JJ, Wang Z, Wang XM, Yang H, Wang MR, Zhou ZX*, Zhang Y*. Analysis of genomic aberrations associated with the clinicopathological parameters of rectal cancer by array comparative genomic hybridization. Oncol Rep, 2013. DOI: 10.3892（in press）

4. Chen X, Zhang TT, Liang JW, Shang L, Huo YQ, Xu X, Zhou ZX, Wang MR, Zhang Y*, Jia XM*. Analysis of PIK3CA gene mutations in Cantonese of Northern China with colorectal cancer. Carcinogenesis, Teratogenesis and Mutagenesis.2012; 24(4):245-8. Chinese

Selected co-author articles

1. Lin DC, Hao JJ, Nagata Y, Meng X, Sato Y, Dr. Okuno Y, Xu L, Varela A, Ding LW, Garg M, Liu LZ, Yang H, Shi ZZ, Shang L, Jiang YY, Gu WY, Gong T, Zhang Y, Xu X, Kalid O, Shacham S, Ogawa S, Wang MR, Koeffler HP, Yin D. Genomic and molecular characterization of esophageal squamous cell carcinoma. Nature Genetics, 2014 (accepted)

2. Shi ZZ, Shang L, Jiang YY, Hao JJ, Zhang Y, Zhang TT, Lin DC, Liu SG, Wang BS, Gong T, Zhan QM, and Wang MR*. Consistent and differential genetic aberrations between esophageal dysplasia and squamous cell carcinoma detected by array comparative genomic hybridization. Clin Cancer Res. 2013, 19(21):5867-5878.

3. Wang BS, Yang Y, Lu HZ, Shang L, Zhang Y, Hao JJ, Shi ZZ, Wang XM, Liu YZ, Zhan QM, Jia XM and Wang MR*. Protein-Tyrosine Phosphatase 1B Contributes to Calreticulin-Induced Cell Migration and Metastasis of Esophageal Squamous Cell Carcinoma. Mol Cancer Res. 2013, 11(9):986-994.

4. Wang BS, Yang Y, Yang H, Liu YZ, Hao JJ, Zhang Y, Shi ZZ, Jia XM, Zhan QM and Wang MR*. PKCι counteracts oxidative stress by regulating Hsc70 in an esophageal cancer cell line. Cell Stress Chaperones. 2013, 18(3):359-366.

5. Wang BS, Liu YZ, Yang Y, Zhang Y, Hao JJ, Yang H, Wang XM, Zhang ZQ, Zhan QM, Wang MR. Autophagy negatively regulates cancer cell proliferation via selectively targeting VPRBP. Clin Sci (Lond).2013; 124(3): 203-14

6. Hao JJ, Gong T, Zhang Y, Shi ZZ, Xu X, Dong JT, Zhan QM, Fu SB, Wang MR*. Characterization of gene rearrangements resulted from genomic structural aberrations in human esophageal squamous cell carcinoma KYSE150 cells. Gene. 2013, 513(1):196-201. (IF:2.196)

7. Hao JJ, Shi ZZ, Zhao ZX, Zhang Y, Gong T, Li CX, Zhan T, Cai Y, Dong JT, Fu SB, Zhan QM, Wang MR*. Characterization of genetic rearrangements in esophageal squamous carcinoma cell lines by a combination of M-FISH and array-CGH: further confirmation of some split genomic regions in primary tumors. BMC Cancer. 2012, 12:367.

8. Lin DC, Zhang Y, Pan QJ, Yang H, Shi ZZ, Xie ZH, Wang BS, Hao JJ, Xu X, Zhan QM, Wang MR. PLK1 is transcriptionally activated by NF-kB during cell detachment and enhances anoikis resistance through inhibiting beta-catenin degradation in esophageal cancer. Clin Cancer Res. 2011;17: 4285-95.

9. Sun Q, Chen X, Ma J, Peng H, Wang F, Zha X, Wang Y, Jing Y, Yang H, Chen R, Chang L, Zhang Y, Goto J, Onda H, Chen T, Wang MR, Lu Y, You H, Kwiatkowski D, Zhang H. Mammalian target of rapamycin up-regulation of pyruvate kinase isoenzyme type M2 is critical for aerobic glycolysis and tumor growth. Proc Natl Acad Sci USA. 2011;108(10):4129-34.

10. Shi ZZ, Zhan T, Wang BS, Lin DC, Liu SG, Hao JJ, Yang H, Liang JW, Zhang Y, Zhang Y, Zhang KT, Wang MR. Genomic Alterations with Impact on Survival in Esophageal Squamous Cell Carcinoma Identified by Array Comparative Genomic Hybridization. Genes Chromosomes Cancer. 2011; 50(7): 518-26.

11. Liu SG, Wang BS, Jiang YY, Zhang TT, Shi ZZ, Yang Y, Yang YL, Wang XC, Lin DC, Zhang Y, Yang H, Cai Y, Zhan QM and Wang MR. Atypical Protein Kinase Cι (PKCι) Promotes Metastasis of Esophageal Squamous Cell Carcinoma by Enhancing Resistance to Anoikis via PKCι-SKP2-AKT Pathway. Mol Cancer Res. 2011; 9(4):1-13.

12. Du XL, Yang H, Liu SG, Luo ML, Hao JJ, Zhang Y, Lin DC, Xu X, Cai Y, Zhan QM, Wang MR. Calreticulin promotes cell motility and enhances resistance to anoikis through STAT3-CTTN-Akt pathway in esophageal squamous cell carcinoma. Oncogene. 2009; 28(42):3714-22.

13. Li C, Chen H, Ding F, Zhang Y, Luo A, Wang M, Liu Z.A novel p53 target gene, S100A9, induces p53-dependent cellular apoptosis and mediates the p53 apoptosis pathway. Biochem J. 2009; 422(2):363-72.

14. Feng YB, Lin DC, Shi ZZ, Wang XC, Shen XM, Zhang Y, Du XL, Luo ML, Xu X, Han YL, Cai Y, Zhang ZQ, Zhan QM, Wang MR. Overexpression of PLK1 is associated with poor survival by inhibiting apoptosis via enhancement of Survivin level in esophageal squamous cell carcinoma. Int J Cancer. 2009; 124(3): 578-88.

15. Yang YL, Chu JY, Luo ML, Wu YP, Zhang Y, Feng YB, Shi ZZ, Xu X, Han YL, Cai Y, Dong JT, Zhan QM, Wu M, Wang MR. Amplification of PRKCI, located in 3q26, is associated with lymph node metastasis in esophageal squamous cell carcinoma. Genes Chromosomes Cancer. 2008; 47(2):127-36.

16. Shen XM, Wu YP, Feng YB, Luo ML, Du XL, Zhang Y, Cai Y, Xu X, Han YL, Zhang X, Zhan QM, Wang MR. Interaction of MT1-MMP and laminin-5 gamma2 chain correlates with metastasis and invasiveness in human esophageal squamous cell carcinoma. Clin Exp Metastasis. 2007; 24(7):541-50.

17. Du XL, Hu H, Lin DC, Xia SH, Shen XM, Zhang Y, Luo ML, Feng YB, Cai Y, Eu X, Han YL, Zhan QM, Wang MR. Proteomic profiling of proteins dysregulted in Chinese esophageal squamous cell carcinoma. J Mol Med. 2007; 85(8): 863-75. [http://f1000.com/13353990#evaluations]

18. Luo ML, Shen XM,Zhang Y, Wei F, Xu X, Cai Y, Zhang X, Sun YT, Zhan QM, Wu M, Wang MR. Amplification and overexpression of CTTN (EMS1) contribute to the metastasis of esophageal squamous cell carcinoma by promoting cell migration and anoikis resistance. Cancer Res. 2006; 66(24):11690-9.

19. Guan XY, Fung JM, Ma NF, Lau SH, Tai LS, Xie D, Zhang Y, Hu L, Wu QL, Fang Y, Sham JS: Oncogenic Role of eIF-5A2 in the Development of Ovarian Cancer. Cancer Res. 2004; 64 (12): 4197-200.

Honors and awards

1. Zhang Y, Wu Min Medical Genetics Innovation Awards, 2013.

2. Wang MR, Zhang Y, Xu X, Han YL, Cai Y, Luo ML, Du XL, Yang YL, et al. Study of molecular alterations and related mechanisms in the development and progression of esophageal squamous cell carcinoma. The third prize of Science and Technology Award, 2008. Chinese Medical Association. 200803034U0101, 2008.12.21.

3. Wang MR, Xu X, Han YL, Cai Y, Hu H, Luo ML, Du XL, Zhang Y, et al. Molecular mechanisms of esophageal cancer development and progression. The second prize of Natural Science Award of higher school science research outstanding achievement, 2008. The ministry of education. 2008-08.

4. Fu S, Wang BQ, Yan CH, Bai J, Jin Y, Wang Q, Zhang QF, Zhang Y, et al. Chromosomal and tumor related gene alterations in human lung and gastric caners. The first prize of Natural Science Award of higher school science research outstanding achievement, 2003. The ministry of education. 2003-041.