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Graduate Institute of Biomedical Sciences

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張玉生

 

 

 

 

 

 

張玉生(Yu-Sun Chang)

Appointment: Professor

LabVirology Laboratory

Education: Ph.D.

University/NationUniversity of California, Davis, USA

Tel: (03)2118800 ext. 5131

E-mail: ysc@mail.cgu.edu.tw

Research website:

 Research Direction

  1. Nasopharyngeal Carcinoma/Epstein-Barr Virus and Oral Squamous Cell Carcinoma (OSCC)

Nasopharyngeal Carcinoma/Epstein-Barr Virus

The research interest of our lab mostly focused on understanding the role of the Epstein-Barr virus (EBV), a human herpesvirus, in nasopharyngeal carcinoma (NPC). EBV-associated NPC is more prominent in the Chinese from Taiwan, south China, and Hong Kong. The ultimate goal is to understanding the oncogenesis of EBV in NPC development by (1) dissecting the functions of EBV-encoded oncogene latent membrane protein 1 (LMP1), (2) identifying cellular biomarkers that can be used for prognosis of NPC, and (3) exploring the underlined mechanism

Current research focuses on

  1. Inflammsome activation in NPC—mechanism and biomarkers
  2. NPC genome sequencing—genome sequence variations

Oral Squamous Cell Carcinoma (OSCC)

The OSCC research aims to identify biomarkers for early detection, risk prediction, and therapeutic intervention. Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral cancer cases and is among the top five cancers in Taiwan. The major risk factors in Taiwan for OSCC include smoking, alcohol misuse, smokeless tobacco use, and betel quid chewing.

Current research focuses on

  1. Searching for genetic factors that may underline the difference between OSCC in Taiwan and western countries by proteogenomic analysis
  2. Searching for potential therapeutic targets by comparison of proteogenomes in tumor tissues from OSCC patients according to clinical outcome information
  1. International collaboration
  1. The International Cancer Proteogenome Consortium (ICPC), which has partnership with the Cancer Moonshot program initiated in National Cancer Institute, National Institute of Health, USA.
  2. The International Nasopharyngeal Carcinoma Working Group led by the National Cancer Institute, National Institute of Health, USA.

Publications (selected 30/109, 2011-2017)

 1. Lih-Chyang Chen, Chia-Chun Chen, Ying Liang, Ngan-Ming Tsang, Yu-Sun Chang, Chuen Hsueh. 2011. A novel function for TNFAIP2: promotion of migration and metastasis in nasopharyngeal carcinoma. Mod Pathol. 24(2):175-84

2. Hao-Ping Liu, Chih-Ching Wu, Hung-Yi Kao, Yi-Chuan Huang, Ying Liang, Chia-Chun Chen, Jau-Song Yu, Yu-Sun Chang. 2011. Proteome-wide dysregulation by PRA1 depletion delineates a role of PRA1 in lipid transport and cell migration. Mol Cell Proteomics. 2011 Mar;10(3):M900641MCP200.

3. Ka-Po Tse, Wen-Hui Su, Min-lee Yang, Hsiao-Yun Cheng, Ngan-Ming Tsang, Kai-Ping Chang, Sheng-Po Hao, Yin Yao Shugart, and Yu-Sun Chang. 2011. A gender-specific association of CNV 1 at 6p21.3 with NPC susceptibility. Human Molecular Genetics, 20(14):2889-96110.

4. Chiou-Mei Lee, Polong Yang, Lih-Chyang Chen, Chia-Chun Chen, Shinn-Chih Wu, Hsiao-Yun Cheng, Yu-Sun Chang. 2011. A novel role of RASSF9 in maintaining epidermal homeostasis. PLoS ONE 6: Issue 3, e17867. 

5. Wu CS, Chang KP, Chen LC, Chen CC, Liang Y, Hseuh C, Chang YS. 2012. Heterogeneous ribonucleoprotein K and thymidine phosphorylase are independent prognostic and therapeutic markers for oral squamous cell carcinoma. Oral Oncol. 48(6):516-22

6. Hao-Ping Liu, Chia-Chun Chen, Chih-Ching Wu, Yi-Chuan Huang, Shu-Chen Liu, Ying Liang, Kai-Ping Chang, and Yu-Sun Chang. 2012. Epstein-Barr Virus-Encoded Latent Membrane Protein 1 Interacts with FGD4 to Activate Cdc42 and Thereby Promote Migration of Nasopharyngeal Carcinoma Cells. PLoS Pathogens. 8 (5) : e1002690

7. Ka-Po Tse, Chi-Sheng Wu, Chuen Hsueh, Kai-Ping Chang, Sheng-Po Hao, Yu-Sun Chang and Ngan-Ming Tsang. 2012. The Relationship between Secretory Leukocyte Protease Inhibitor Expression and Epstein-Barr Virus Status among Patients with Nasopharyngeal Carcinoma. ANTICANCER RESEARCH 32(4): 1299-1308.

8. Li-Jie Wang, Chia-Wei Hsu, Chiu-Chin Chen, Ying Liang, Lih-Chyang Chen, David M. Ojcius, Ngan-Ming Tsang, Chuen Hsueh, Chih-Ching Wu, and Yu-Sun Chang. 2012. Interactome-wide analysis identifies End-Binding Protein 1 as a crucial component for the speck-like particle formation of activated AIM2 inflammasomes. Mol Cell Proteomics. 11(11):1230-44.132.

9. Lih-Chyang Chen, Li-Jie Wang, Nang-Ming Tsang, David M. Ojcius, Chia-Chun Chen, Chun-Nan OuYang, Chuen Hsueh, Ying Liang, Kai-Ping Chang, Chiu-Chin Chen, and Yu-Sun Chang. 2012. Tumor inflammasome-derived IL-1β recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma. EMBO Mol Med. Dec;4(12):1276-93.

10. Hsu WL, Tse KP, Liang S, Chien YC, Su WH, Yu KJ, Cheng YJ, Tsang NM, Hsu MM, Chang KP, Chen IH, Chen TI, Yang CS, Goldstein AM, Chen CJ, Chang YS (corresponding), Hildesheim A. 2012. Evaluation of Human Leukocyte Antigen-A (HLA-A), Other Non-HLA Markers on Chromosome 6p21 and Risk of Nasopharyngeal Carcinoma. PLoS One.7(8):e42767.

11. Shu-Chen Liu, Ngan-Ming Tsang, Wen-Che Chiang, Chuen Hsueh, Ying Liang, Jyh-Lyh Juang, Kai-Ping N. Chow, Kai-Ping Chang, Yu-Sun Chang. 2013. Leukemia inhibitory factor regulates p70S6K and DNA damage responses to promote progressiveness and radioresistance of nasopharyngeal carcinoma in humans and mice. J Clinical Investigation 123(12):5269-5283

12. Chia-Chun Chen, Hao-Ping Liu, Mei Chao, Ying Liang, Ngan-Ming Tsang, Yu-Sun Chang. 2013. NF-kB-mediated transcriptional upregulation of TNFAIP2 by the Epstein-Barr virus oncoprotein, LMP1, promotes cell motility of nasopharyngeal carcinoma. Oncogene 33(28):3648-59.

13. Li HP, Peng CC, Chung IC, Huang MY, Huang ST, Chen CC, Chang KP, Hsu CL, Chang YS. 2013. Aberrantly hypermethylated homeobox A2 derepresses metalloproteinase -9 through TBP and promotes invasion in nasopharyngeal carcinoma. Oncotarget 4(11):2154-2165.

14. Su WH, Yao Shugart Y, Chang KP, Tsang NM, Tse KP, Chang YS. 2013. How genome-wide SNP-SNP interactions related to nasopharyngeal carcinoma susceptibility. PLoS One 8(12):e83034.

15. Su WH, Hildesheim A, Chang YS. 2013. Human Leukocyte Antigens and Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma: Old Associations Offer New Clues into the Role of Immunity in Infection-Associated Cancers. Front Oncol. 3:299. (Invited Review Article)

16. Chung I-Che, Lih-Chyang Chen, An-Ko Chung, Mei Chao, Chuen Hsueh, Ngan-Ming Tsang, Kai-Ping Chang, Ying Liang, Hsin-Pai Li, and Yu-Sun Chang. 2014. Matrix Metalloproteinase 12 Is Induced by Heterogeneous Nuclear Ribonucleoprotein K and Promotes Migration and Invasion in Nasopharyngeal Carcinoma; BMC Cancer 14(1):348.

17. Shu-Chen Liu and Yu-Sun Chang. 2014. Role of leukemia inhibitory factor in nasopharyngeal carcinogenesis. Molecular and Cellular Oncology Vol 1(1):e29900. (Invited review article)

18. Hsin-Pai Li, Hsin-Yi Huang, Yi-Ru Lai, Jing-Xuan Huang, Kai-Ping Chang, Chuen Hsueh and Yu-Sun Chang. 2014. Silencing of miRNA-148a by hypermethylation activates the integrin-mediated signaling pathway in nasopharyngeal carcinoma. Oncotarget 5(17):7610-24

19. Li-Jie Wang, Hsin-Yi Huang, Meng-Pin Huang, Willisa Liou, Ya-Ting Chang, Chih-Ching Wu, David M. Ojcius and Yu-Sun Chang. 2014. The Microtubule-Associated Protein, EB1, Links AIM2 Inflammasomes with Autophagy-Dependent Secretion. J. Biol. Chem. 289(42):29322-33.

20. Wu TS, Wang LC, Liu SC, Hsu TY, Lin CY, Feng GJ, Chen JM, Liu HP, Chung IC, Yen TC, Chang YS, Liao SK, Chang C, Chow KP. 2015. EBV Oncogene N-LMP1 Induces CD4 T Cell-Mediated Angiogenic Blockade in the Murine Tumor Model. J Immunol. 194(9):4577-4587

21. Chen SJ, Liu H, Liao CT, Huang PJ, Hus A, Tang P, Chang YS, Chen HC, Yen TC. 2015. Ultra-deep targeted sequencing of advanced oral squamouse cell carcinoma identifies a mutation-based prognostic gene signature. Oncotarget Jul 20;6(20):18066-80.

22. Hsu CL, Kuo YC, Huang Y, Huang YC, Lui KW, Chang KP, Lin TL, Fan HC, Lin AC, Hsieh CH, Lee LY, Wang HM, Li HP, Chang YS. 2015. Application of a patient-derived xenograft model in cytolytic viral activation therapy for nasopharyngeal carcinoma. Oncotarget. 6(31):31323-34.

23. Jin-Xin Bei, Wen-Hui Su, Ching-Ching Ng, Kai Yu,Yoon-Ming Chin, Pei-Jen Lou, Wan-Lun Hsu, James D. McKay, Chien-Jen Chen, Yu-Sun Chang, Li-Zhen Chen, Ming-Yuan Chen, Qian Cui, Fu-Tuo Feng, Qi-Shen Feng,Yun-Miao Guo,Wei-Hua Jia, Alan Soo-Beng Khoo,Wen-Sheng Liu, Hao-Yuan Mo, Kin-Choo Pua, Soo-Hwang Teo, Ka-Po Tse, Yun-Fei Xia, Hongxin Zhang, Gang-Qiao Zhou, Jian-Jun Liu, Yi-Xin Zeng, and Hildesheim Allan on behalf of the International Nasopharyngeal Carcinoma (NPC) Genetics Working Group. 2015. A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry.  CANCER EPIDEMIOLOGY, BIOMARKERS & PREVENTION 25(1):188-92.

24. Wu CS, Chang KP, OuYang CN, Kao HK, Hsueh C, Chen LC, Cheng HY,

Liang Y, Liou W, Liang CL, Chang YS. 2016. ASC contributes to metastasis of oral cavity squamous cell carcinoma. Oncotarget. 7(31):50074-50085.

25. Yu JS, Chen YT, Chiang WF, Hsiao YC, Chu LJ, See LC, Wu CS, Tu HT, Chen HW, Chen CC, Liao WC, Chang YT, Wu CC, Lin CY, Liu SY, Chiou ST, Chia SL, Chang KP, Chien CY, Chang SW, Chang CJ, Young JD, *Chang YS, *Hartwell LH. 2016. Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan. Proc Natl Acad Sci U S A. 113(41):11549-11554. (co-Corresponding author)

26. I-Che Chung, Chun-Nan OuYang, Sheng-Ning Yuan, Hsin-Pai Li, Jeng-Ting Chen, Hui-Ru Shieh, Yu-Jen Chen, David Ojcius, Ching-Liang Chu, Jau-Song Yu, Yu-Sun Chang, and Lih-Chyang Chen. 2016. Pyk2 activates the NLRP3 inflammasome by directly phosphorylating ASC and contributes to inflammasome-dependent peritonitis" Scientific Reports 6:36214.

27. Telomeres Mendelian Randomization Collaboration., Haycock PC, Burgess S, Nounu A, ….Chang KP, Su WH, Chang YS, .. Davey Smith G. 2017.  Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study. JAMA Oncol. 2017 May 1;3(5):636-651.

28. Chen Ting-Wen, Chi-Ching Lee, Hsuan Liu, Chi-Sheng Wu, Curtis R. Pickering, Po-Jung Huang, Jing Wang, Ian Yi-Feng Chang, Yuan-Ming Yeh, Chih-De Chen, Hsin-Pai Li, Ji-Dung Luo, Bertrand Chin-Ming Tan, Timothy En Haw Chan, Chuen Hsueh, Lichieh Julie Chu, Yi-Ting Chen, Bing Zhang, Chia-Yu Yang, Chih-Ching Wu, Chia-Wei Hsu, Lai-Chu See, Petrus Tang, Jau-Song Yu, Wei-Chao Liao, Kenny W.F. Chiang, Henry Rodriguez, Ming-Huei Cheng, Jeffrey N. Myers, Kai-Ping Chang, Yu-Sun Chang. 2017. APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism.Nat Commun.;8(1):465.

29. Li HP, Peng CC, Wu CC, Chen CH, Shih MJ, Huang MY, Lai YR, Chen YL,

Chen TW, Tang P, Chang YS, Chang KP, Hsu CL. Inactivation of the tight junction gene CLDN11 by aberrant hypermethylation modulates tubulins polymerization and promotes cell migration in nasopharyngeal carcinoma.  J Exp Clin Cancer Res. 2018 May 10;37(1):102. doi: 10.1186/s13046-018-0754-y

30. Hsin-Pai Li, Cheng-Lung Hsu, Yu-Sun Chang. 2018. Screening of nasopharyngeal carcinoma using plasma Epstein-Barr virus DNA for at-risk population. Annals of Nasopharynx Cancer. (Editorial) doi: 10.21037/anpc.2018.03.01

 

 

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