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黎欣白

黎欣白 (Hsin-Pai Li)

職稱:副教授

研究室名稱:腫瘤病毒及癌症研究

最高學歷:Ph.D.

學校/國家:University of Southern California/ USA (Department of Microbiology)

分機號碼:3593

電子郵件帳號:paili@mail.cgu.edu.tw

實驗室:第一醫學大樓7F Rm 0757

研究室現有: 碩士生2 大學生 2

博士班已畢業2

碩士班已畢業10

專任研究助理 2 人

大學部專題生 2 0人

 

101學年:  優良教師獎 (醫學院基礎教學)

103學年:  優良教師獎 (醫學院輔導類)

研究方向:

(1) 腫瘤病毒 EBV  (2) 癌症研究  (3) DNA甲基化

研究室特色 (2015/12)

鼻咽癌(NPC)是與EB病毒密切相關的一種惡性腫瘤,好發於鼻咽鱗狀上皮細胞。在鼻咽癌檢體常發現有許多基因的缺失,其中包括致癌基因(Oncogenes)的活化以及抑癌基因(Tumor Suppressor Genes)的去活化。在腫瘤形成過程中,藉由表觀遺傳(Epigenetics)的修飾,如DNA甲基化 (DNA methylation),可導致基因的去活化。我們曾報導在鼻咽癌組織中EB病毒的致癌基因潛伏膜蛋白1”(LMP1),可活化細胞的DNA甲基轉移酶 (DNMT1)的表現,導致DNA過度甲基化,這可能跟鼻咽癌之致病機轉有密切關係。在癌細胞中,基因起動子區域之不正常甲基化,往往造成抑癌基因無法表現,進而促使癌症的發生。因此, DNMT1的作用目標基因亦可被視為抑癌基因的候選基因。除了一般的基因,DNA甲基化也同樣可抑制~22核苷酸之微型核醣核酸(miRNA)基因的表現,由於每一種miRNA均具有調降 ~1000 mRNA的產量,因此抑癌-miRNA基因不正常的甲基化(抑癌-miRNA可調降致癌基因的表現),反而促進癌化的現象。本實驗室主要研究方向為(1)鑑別以及驗證在鼻咽癌細胞中潛在甲基化的差別抑癌基因miRNA基因(2) 檢測鼻咽癌細胞株甲基化miRNA基因原來調控的目標mRNA(3)瞭解這些甲基化抑癌基因及miRNA基因在鼻咽癌中的生理功能。

     以免疫沈澱法ChIP-seq分離在鼻咽癌細胞株(C666.1)及正常鼻咽細胞株(NP69)甲基程度較高的DNA,並以定序方式分析及比較上述這兩種細胞株中甲基程度較高的DNA序列。其中鼻咽癌細胞株C666.1甲基化程度較高的DNA區域以紅線標示在23條染色體上。此圖顯示部分染色體的位置有明顯高度甲基化的情形,代表在鼻咽癌細胞中某此基因有可能受甲基化所影響,可進一步探討它們的基因表達是否受到抑

 

 

Aberrantly hypermethylated transcription repressor homeobox A2 derepresses metalloproteinase-9 activity through TBP and promotes invasion in nasopharyngeal carcinoma. (Oncotarget 2013; 4:2154-2165)

A differential hypermethylated transcription repressor, Homeobox A2 (HOXA2), is identified in NPC tumor, which may render NPC cells invasive and metastaic. Aberrant hypermethylation of HOXA2 led to low RNA expression in NPC tumors and cells. Addition of methylation inhibitor 5’aza restored HOXA2 RNA expression in NPC cells. Methylated HOXA2 promoter reduces the binding affinity of the transcriptional co-activator p300, causing transcriptional repression of HOXA2. In NPC cells, re-expression of ectopic HOXA2 was correlated with decreased invasive ability and reduced metalloproteinase MMP-9 RNA and protein expression. Promoter, ChIP and DNA-pull down assays indicated that HOXA2 competes with the transcription activator, TATA-box binding protein (TBP) for a recognition sequence near the MMP-9 transcription start site, and suppresses MMP-9 transcription. Thus, HOXA2 acts as a suppressor or TBP-antagonist to inhibit MMP-9 expression; while methylation-mediated inactivation of HOXA2 in NPC derepresses MMP-9 production and increases invasion of NPC cells. In NPC plasma samples, increased plasma EBV copy number was correlated with increased in cell-free HOXA2 hypermethylation and elevated MMP-9 levels.

 

 Oncotarget 2013; 4:2154-2165

 

Silencing of miRNA-148a by hypermethylation activates the integrin-mediated signaling pathway in nasopharyngeal carcinoma.

(Oncotarget 2014; (5)17:7610-24)

MiRNA-148a is downregulated through hypermethylation in NPC biopsies and NPC cell lines compared with adjacent normal and NP cells respectively. Promoter assays demonstrated that upstream stimulatory factor 1 (USF1) is a crucial transcription factor that activates miR-148a promoter activity. EMSA assays confirmed that purified USF1 binds better toward the unmethylated than the methylated CG-containing USF1 consensus probe. The ectopic expression of miR-148a inhibits cell migration in NPC cells through the suppression of integrin-mediated signaling by targeting VAV2, WASL and ROCK1. Furthermore, immunohistochemical staining and Western blotting analysis revealed that the 3 oncogenic targets of miR-148a were overexpressed in NPC biopsies, suggesting that the inactivation of miR-148a caused by DNA methylation promotes NPC progression. Overall, our findings revealed that miR-148a can act as tumor suppressor miRNA for NPC.

 

 

  Oncotarget 2014 July; (5)17:7610-24

 

 

 

Cheng-Lung Hsu, Yung-Chia Kuo, Yenlin Huang, Yin-Cheng Huang, Kar-Wai Lui, Kai-Ping Chang, Tung-Liang Lin, Hsien-Chi Fan, An-Chi Lin, Chia-Hsun Hsieh, Li-Yu Lee, Hung-Ming Wang, Hsin-Pai Li, Yu-Sun Chang

Application of a patient-derived xenograft model in cytolytic viral activation therapy for nasopharyngeal carcinoma

Oncotarget 2015 Sept., advanced online publication (IF=6.627; R/C= 17/203; ONCOLOGY)

 

Hsin-Pai Li*, Hsin-Yi Huang, Yi-Ru Lai, Jing-Xuan Huang, Kai-Ping Chang, Chuen Hsueh and Yu-Sun Chang (Co-first author; *Corresponding)

Silencing of miRNA-148a by hypermethylation activates the integrin-mediated signaling pathway in nasopharyngeal carcinoma

Oncotarget 2014 July; (5)17:7610-24 (IF=6.627; R/C= 17/203; ONCOLOGY)

 

Ting-Wen Chen†, Hsin-Pai Li, Chi-Ching Lee, Ruei-Chi Gan, Po-Jung Huang, Timothy H Wu,

Cheng-Yang Lee, Yi-Feng Chang and Petrus Tang (Co-first author)

ChIPseek, a web-based analysis tool for ChIP data

BMC Genomics 2014 Jun, 15:539 (IF=4.041; R/C=29/165; BIOTECHNOLOGY & APPLIED MICROBIOLOGY)

 

I-Che Chung†, Lih-Chyang Chen†, An-Ko Chung, Mei Chao, Hsin-Yi Huang, Chuen Hsueh,Ngan-Ming Tsang, Kai-Ping Chang, Ying Liang, Hsin-Pai Li* and Yu-Sun Chang* (*Co-corresponding)

Matrix metalloproteinase 12 is induced by heterogeneous nuclear ribonucleoprotein K and promotes migration and invasion in nasopharyngeal carcinoma

BMC Cancer 2014 May, 14:348-361 (IF=3.319; R/C=74/202; ONCOLOGY)

Hsin-Pai Li*+, Chen-Ching Peng*, I-Che Chung, Mei-Yuan Huang, Shao-Tung Huang, Chia-Chun Chen, Kai-Ping Chang, Cheng-Lung Hsu, Yu-Sun Chang (* Co-first author; + Corresponding)

Aberrantly Hypermethylated Transcription Repressor Homeobox A2 Derepresses Metalloproteinase-9 Activity Through TBP and Promotes Invasion in Nasopharyngeal Carcinoma

Oncotarget 2013; 4:2154-2165 (IF=6.636; R/C= 21/197; ONCOLOGY)

Cheng-Lung Hsu, Kai-Ping Chang, Chien-Yu Lin, Hsien-Kun Chang, Cheng-Hsu Wang, Tung-Liang Lin, Chun-Ta Liao, Ngan-Ming Tsang, Li-Yu Lee, Sheng-Chieh Chan, Shu-Hang Ng, Hsin-Pai Li, Yu-Sun Chang and Hung-Ming Wang

Plasma EBV DNA Concentration and Clearance Rate as Novel Prognostic Factors for Metastatic Nasopharyngeal Carcinoma

Head & Neck 2011; DOI: 10.1002/hed.21890 (IF=2.833; R/C= 3/43, OTORHINOLARYNGOLOGY)

Chia-Chen Hsu+, Hsin-Pai Li+ , Yu-Hung Hung , Yu-Wei Leu , Wu-Hsiung Wu, Feng-Sheng Wang , Kuan-Der Lee , Pey-Jium Chang , Chi-Sheng Wu, Yen-Jung Lu , Tim H.-M. Huang, Yu-Sun Chang, Shu-Huei Hsiao (+ Co-first author)

Targeted Methylation of CMV and E1A viral promoters

Biochemical and Biophysical Research Communications 2010; 402: 228–234

(IF=2.484; R/C= 39/74, BIOPHYSICS)

Hsin-Pai Li, Mei Chao, Su-Jen Chen, Yu-Sun Chang

Epstein-Barr Virus

World Scientific Publishing, Oncogenic Virus, Invited Chapter 2010

Yen-Jung Lu, Chi-Sheng Wu, Hsin-Pai Li+, Hao-Ping Liu, Chang-Yi Lu, Yu-Wei Leu, Chia-Siu Wang, Lih-Chyang Chen, Kwang-Huei Lin, and Yu-Sun Chang+ (+Co-corresponding) Aberrant Methylation Impairs Low Density Lipoprotein Receptor-Related Protein 1B (LRP1B) Tumor Suppressor Function in Gastric Cancer.

Genes, Chromosomes and Cancer 2010; 49(5):412-24. (IF=3.546; R/C= 53/158; Genetics & Heredity)

Chi-Sheng Wu, Yen-Jung Lu, Hsin-Pai Li, Chuen Hsueh, Chang-Yi Lu, Yu-Wei Leu, Hao-Ping Liu, Kwang-Huei Lin, Tim Hui-Ming Huang and Yu-Sun Chang

Glutamate receptor, ionotropic, kainate 2 silencing by DNA hypermethylation possesses tumor suppressor function in gastric cancer.

International Journal of Cancer 2010; 126: 2542–2552  (IF=6.198; R/C= 23/196; Oncology)

 

Lih-Chyang Chen, Hao-Ping Liu, Hsin-Pai Li, Chuen Hsueh, Jau-Song Yu, Ying Liang, Yu-Sun Chang

Thymidine phosphorylase mRNA stability and protein levels are increased through ERK-mediated cytoplasmic accumulation of hnRNP K in nasopharyngeal carcinoma cells.

Oncogene 2009; Apr 30; 28(17):1-12. (IF=7.357; R/C= 19/196; Oncology)

Ka-Po Tse, Nang-Ming Tsang, Kung-Den Chen, Hsin-Pai Li, Ying Liang, Chuen Hsueh, Kai-Ping Chang, Jau-Song Yu, Sheng-Po Hao, Ling-Ling Hsieh, and Yu-Sun Chang

MCP-1 Promoter Polymorphism at -2518 is Associated with Metastasis of Nasopharyngeal Carcinoma after Treatment.

Clinical Cancer Research 2007; 13: 6320-6326. (IF=7.837; R/C= 12/196; Oncology)

Chia-Lung Tsai*, Hsin-Pai Li*, Chuen Hsueh, Ying Liang, Chi-Long Chen, Sai Wah Tsao, Ka-Po Tse, Yen-Jung Lu, Jau-Song Yu and Yu-Sun Chang (* Co-first author)

Activation of DNA methyltransferase 1 by Epstein-Barr Virus LMP1 involves JNK signaling. Cancer Research 2006; 66:11668-11674. (IF=8.650; R/C= 11/196; Oncology)

Lee YN, Chen LK, Ma HC, Yang HH, Li HP, Lo SY

Thermal aggregation of SARS-CoV membrane protein

J Virological Methods 2005 Jul; 129:152-161 (IF= 1.883; R/C= 90/165; BIOTECHNOLOGY & APPLIED MICROBIOLOGY)

Li HP, Leu YW, Chang YS.

Epigenetic changes in virus-associated human cancers

Cell Research 2005 Apr; 15(4):262-271 (IF=8.190; R/C= 23/180; cELL BIology)

Li HP, Chang YS.
Epstein-Barr virus latent membrane protein 1: structure and functions.

J. Biomedical Science 2003 Sep-Oct; 10:490–504  (IF=1.980; R/C= 63/112; MEDICINE, RESEARCH & EXPERIMENTAL)

Yu JS, Tsai HC, Wu CC, Weng LP, Li HP, Chung PJ, Chang YS.
Induction of inducible nitric oxide synthase by Epstein-Barr virus B95-8-derived LMP1 in Balb/3T3 cells promotes stress-induced cell death and impairs LMP1-mediated transformation.

Oncogene, 2002 Nov 14;21(52):8047-61 (IF=7.357; R/C= 19/196; Oncology)

Shi ST, Huang P, Li HP, Lai MM.
Heterogeneous nuclear ribonucleoprotein A1 regulates RNA synthesis of a cytoplasmic virus.

EMBO J 2000 Sep 1;19(17):4701-11  (IF=10.748; R/C= 15/291; BIOCHEMISTRY & MOLECULAR BIOLOGY)

Zhang X, Li HP, Xue W, Lai MM.
Formation of a ribonucleoprotein complex of mouse hepatitis virus involving heterogeneous nuclear ribonucleoprotein A1 and transcription-regulatory elements of viral RNA.

Virology 1999 Nov 10;264(1):115-24 (IF=3.278; R/C= 16/33; VIROLOGY)

Li HP, Huang P, Park S, Lai MM.
Polypyrimidine tract-binding protein binds to the leader RNA of mouse hepatitis virus and serves as a regulator of viral transcription.

J Virol 1999 Jan;73(1):772-7 (IF=4.648; R/C= 7/33; VIROLOGY)

Zhang X, Li HP, Xue W, Lai MM.
Cellular protein hnRNP-A1 interacts with the 3'-end and the intergenic sequence of mouse hepatitis virus negative-strand RNA to form a ribonucleoprotein complex.

Adv Exp Med Biol 1998;440:227-34 (IF=3.278; R/C= 16/33; VIROLOGY)

Kraeft SK, Chen DS, Li HP, Chen LB, Lai MM.
Mouse hepatitis virus infection induces an early, transient calcium influx in mouse astrocytoma cells.

Exp Cell Res 1997 Nov 25;237(1):55-62 (IF=2.012; R/C=24/85 ; BIOLOGY)

Li HP, Zhang X, Duncan R, Comai L, Lai MM.
Heterogeneous nuclear ribonucleoprotein A1 binds to the transcription-regulatory region of mouse hepatitis virus RNA.

Proc Natl Acad Sci U S A 1997 Sep 2;94(18):9544-9 (IF=9.809; R/C= 4/55; MULTIDISCIPLINARY SCIENCES)

Chen DS, Asanaka M, Yokomori K, Wang F, Hwang SB, Li HP, Lai MM.
A pregnancy-specific glycoprotein is expressed in the brain and serves as a receptor for mouse hepatitis virus.

Proc Natl Acad Sci U S A 1995 Dec 19;92(26):12095-9 (IF=9.809; R/C= 4/55; MULTIDISCIPLINARY SCIENCES)

 Lai MY, Chang HC, Li HP, Ku CK, Chen P J, Sheu J C, Huang G T, Lee PH, Chen DC.
Splicing mutations of the p53 gene in human hepatocellular carcinoma.

Cancer Research 1993 Apr 1;53(7): 1653-6 (IF=9.284; R/C= 10/203; ONCOLOGY)

 

 

 

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