Dr. Yu-Sun Chang, Professor
Graduate Institute of Basic Medical Sciences, Chang-Gung University
Phone: 886-3-211-8800 #5131
1971, B.S.¡@ Botany
¡@¡@¡@¡@¡@¡@ National Chung-Hsing University, Taiwan
1973, M.S.¡@ Botany
¡@¡@¡@¡@¡@¡@ Brigham Young Universiyt, Provo, Utah, USA
¡@¡@¡@¡@¡@¡@ University of California, Davis, Ca, USA
¡@The major research interest of the DR. Chang's laboratory is to understand the role of Epstein-Barr virus (EBV) in the development of nasopharyngeal carcinoma (NPC). Approaches have been taken to understand the mechanisms at both viral and cellular levels. Specific studies focus on regulation and function of EBV oncogene, latent membrane protein 1 (LMP 1) that is expressed in the tumor tissues.
1. To study the LMP 1 function through its interacting proteins. We have reported that a variant form of LMP 1 is present in NPC biopsies (designated as NLMP 1). This NLMP 1 is more tumorigenic than the wild type LMP 1 (BLMP 1 as derived from a B cell line). These include search for cellular protein(s) that is (are) associated with NLMP 1 and effect of this protein-protein association on LMP 1-mediated functions including LMP 1-induced transformation, target gene activation and LMP-mediated cell signaling.
2. To determine the signaling pathways which are involved in LMP1-induced DNA methyltransferase 1 gene expression. We have reported that LMP1 induced cellular DNA methyltransferase 1, which results in hypermethylation of its target genes such as E-cadherin. Hypermethylation of E-cadherin promoter results in down-regulation of E-cadherin and enhanced cell migration activity. We investigate the mechanisms of this activation using LMP1 mutants and siRNA targeting specific cellular molecules.
3. To investigate LMP1-induced transcription repression complex. We are interested in investigate the components in the transcription repression complex induced by LMP1-induced DNA methylation.
4. To examine the role of LMP1 through LMP1-interacting proteins. We have identified several LMP1 interacting proteins by the yeast two-hybrid screen. We examine the role of these proteins in LMP1-mediated functions such as cell transformation and cell migration activity as well as specific signaling pathways. We also examine the physiological role of the interacting proteins in model organisms such as zebrafish.
1. Tsai, Chi-neu, Chiu-mei Lee, Chih-kai Chien, Szu-cheng Kuo and Yu-sun Chang. 1999. Additive effect of Sp1 and Sp3 in regulation of the ED-L1E promoter of EBV LMP 1 gene in human epithelial cells. Virology 261: 288-294.
2. Wang, Chun-chieh, Mong-liang Chen, Kuang-hung Hsu, Steve P Lee, Tse-ching Chen, Yu-sun Chang, Ngan-ming Tsang and Ji-hing Hong. 2000. Second malignant tumors in patients with nasopharyngeal carcinoma and their association with Epstein-Barr virus. Int. J. Cancer 87: 228-231.
3. Liang, Chih-lung, Chi-neu Tsai, Pei-rong Chung, Cheng-ming Sun, Jo-lin Chen, Ruey-hwa Chen, and Yu-sun Chang. 2000. Transcription of Epstein-Barr virus nuclear antigen 1 promoter Qp is repressed by transforming growth factor ƒÒƒnvia Smad4 binding element in human BL cells. Virology 277: 184-197.
4. Chow, KP, HC Lu, HF Chou, HP Liu, SL Hsieh, YS Chang, and KB Choo. 2002. Induction of chemosensitivity in nasopharyngeal carcinoma cells using a human papillomavirus regulatory sequence and the thymidine kinase gene. J. Biomed Sci 9: 41-46.
5. Liang, Chih-lung, Jo-lin Chen, Yun-pung Paul Hsu, Jonthan T. Ou, and Yu-sun Chang. 2002. Epstein-Barr virus BZLF1 gene is activated by transforming growth factor-beta through cooperativity of Smads ad c-Jun/c-Fos proteins. J. Biol. Chem. 277: 23345-23357
6. Yu, Jau-song, Hsing-chen Tsai, Li-ping Weng, Pei-jung Chung, hsin-pai Li, and Yu-sun Chang. 2002. Induction of inducible nitric oxide synthtase by Epstein-Barr virus B95-8-derived LMP1 in Balb/3T3 cells promotes stress-induced cell death and impairs anchorage-independent growth. Oncogene 21: 8047-8061
7. Tsai, Chi-Neu, Chia-lung Tsai, Ka-Po Tse, Hwan-You Chang, and Yu-Sun Chang. 2002. The Epstein-Barr virus oncogene product latent membrane protein 1 induces DNA methyltransferases to down-regulate E-cadherin gene expression. PNAS 99: 10084-10089
8. Chung, Pei-Jung, Yu-Sun Chang, Chih-lung Liang, and Ching-Liang Meng. 2002. Negative Regulation of the Epstein-Barr Virus Latent Membrane Protein 1-mediated functions by BMPR-IA Binding Protein BRAM1. J. Biol. Chem. 277: 39850-39857
9. Chi, Lang-Ming, Jau-Song Yu, and Yu-sun Chang. 2002. Identification of protein kinase CK2 as a potent kinase of Epstein-Barr virus latent membrane protein1. BBRC 294: 586-591
10. Lin, Chen-Lung, Wei-Feng Lo, Tzong-Hsien Lee, Yi Ren, Shiuh-Lin Hwang, Yu-Fan Cheng, Chao-Long Chen, Yu-Sen Chang, Steve P. Lee, Alan B. Rickinson, and Paul Kwong Hang Tam. 2002. Immunization with Epstein-Barr virus (EBV) peptide-pulsed dendritic cells induces functional CD8+ T-cell immunity and may lead to tumor regression in patient with EBV-positive nasopharyngeal carcinoma. Cancer Research 62: 6952-6958
11. Hsieh, Yu-Hua, Chang-jer Wu, Kai-Ping Chow, Chia-Lung tsai, and Yu-Sun Chang. 2003. Electroporation-mediated and EBV LMP1-reulated gene therapy in immunocompetent mouse tumor model. Cancer Gene Therapy 10: 626-636
12. Li, Hsin-Pai and Yu-Sun Chang. 2003. Epstein-Barr Virus Latent Membrane Protein 1: Structure and Functions. J. Biomedical Sciences 10: 490-504
13. Fang, Chih-Yeu, Yu-sun Chang, Kai-Ping Chow, Jao-Song Yu, and Hwan-You Chang. 2004. Construction and characterization of monoclonal antibodies specific to Epstein-Barr virus latent membrane protein 1. J. Immunological Methods 287: 21-30
14. Wu, Chih-ching, Kuan-yi Chien, Ngan-ming Tsang, Kai-ping Chang, Shen-po Hao, Chuang-hui Tsao, Yu-sun Chang, and Jao-song Yu. 2005. Cancer cell-secreted proteomes as a basis for searching potential tumor markers-nasopharyngeal carcinoma as a model. Proteomics 5(12):3173-82
15. Pan, YR, Fang CY, Chang YS, and Chang HY. 2005. Analysis of Epstein-Barr virus gene expression upon phorbol ester and hydroxyurea treatment by real-time quantitative PCR. Archives of Virology 150:755-770
16. Li, Hsin-Pai, Leu Yu-Wei, and Chang Yu-sun. 2005. Epigenetic changes in virus-associated human cancers. Cell Research 15:262-271
17. Wu, Kang-Mai, Chang-Jen Huang, Sheng-Ping Hunag, and Yu-Sun Chang. 2005. Molecular cloning, expression and characterization of the zebrafish bram1 gene, a BMP receptor-associated molecule" J. Biomedical Sciences (accepted)
18. Hsieh, Yu-Hua, Hao-Ping Liu, Szechang J. Lo, and Yu-Sun Chang. 2005. Tumor regression by expression of high physiological levels of EBV latent membrane protein 1. Cancer Biology & Therapy (accepted)
Members of Laboratory