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1 長庚大學臨床醫學研究所教師個人資料表一個人基本資料教師姓名職級教學年資到職日蔡七女助理教授 8 年 93, 10, 18 學歷專長博士學士病毒學, 基因調控陽明大學微生物暨免疫研究所中興大學植物系榮譽教師專長與類組發展方向與特色之關連性 Ching O Medal in Chung-Hsing University (January, 1990) Golden Key Medal in Chung-Hsing University (June, 1990) Member of Phi-Tau Phi Scholastic Honor Society (June, 1990) The Rotary Scholarship ( ) 國科會助理研究學者獎助 (2004) 臨研所之設立便是希望能結合臨床與基礎之研究, 而長庚醫院的特色在於臨床病人多而且具豐富的臨床資料庫可提供相關基礎研究. 本人之前的專長為病毒學及基因調控, 因此未來之研究將注重在病毒引起之感染症, 及腫瘤細胞之基因調控及基因體學研究. 二經歷 ( 一 ) 學術經歷 ( 請填曾任職服務之學術機構, 其中起訖年月請以民國. 月份表示 ) 服務機構服務部門職稱起訖年月長庚大學臨床醫學研究所助理教授 2004/10~ present 長庚大學基研所助理研究學者 2004/8~ 2004/10 長庚大學基研所博士後研究員 1997/8~ 2004/7 三研究研究 (A). Genomic evolution of Norovirus (NoV) in Northern Taiwan The incidence of noroviral gastroenteritis has dramatically increased over the years, and the norovirus (NoV) GII.4 subtype was associated with many sporadic outbreaks worldwide due to rapid mutation and recombination. So, we are interesting about the genomic evolution of NoV in Northern Taiwan and its clinical impact. Therefore, we surveyed the NoV GII.4 subtype and recombinants isolated from hospitalized children with acute gastroenteritis (AGE) in northern Taiwan Northern since 2006 to present. Phylogenetic analysis was performed with 28 NoV samples for completely sequenced genomes; whereas the recombinant of NoV was identified by SimPlot Analysis. We found that the isolated circulating NoV GII.4 subtypes in Nortern Taiwan could be divisible into Hunter, 2006b, and 2009 lineage during 2006~2010. The GII.4 pandemic variant 2006b was predominant circulating during the period, which was gradually replaced by the GII variant after the end of 2009 in northern Taiwan. The different recombinant NoV strains isolated from northern Taiwan during 2006~2010 were identified as intersub-genotype (GII a/GII b, GII a/2008b and 第 1 頁, 共 8 頁

2 GII a/2008a) recombinants. (B). Development of in vitro Norovirus replication system Human Noroviruse (NoV) belong to the members of the family Caliciviridae with single positive stranded RNA genome about 7.5 Kbp. hnov are the dominant cause of outbreaks of gastroenteritis either in adult or infant acute gastroenteritis (AGE) worldwide since 2006, posing severe threat to public health. However the progress in understanding the molecular characteristics of hnov and its replication strategies have been hampered due to lack of a cell culture system or a practical animal model, except for murine NoVs. To understand the replication of the hnov genome, host/viral interaction map and developing anti-viral strategies, we plan to development of an in vitro optimized RNA-based human norovirus reverse genetics system. A complete genome of a human NoV will cloned downstream of a T7 RNA polymerase promoter and expressed in human CACO-2 or other colon cancer cells using T7 RNA polymerase system. The stable hnov replicon system will lead to new insights into its replication, virus host interactions, and approaches for the treatment of hnov diseases. (C). Mixed Sequence Reader (MSR) for Analyzing DNA sequences with heterozygous base calling chromatography to detect genomic variations with a reference database. Heterozygous base-calling fluorescence chromatogram data frequently appear in single nucleotide polymorphisms (SNP), insertion-deletion (Indel), short tandem repeat, and paralog gene when PCR products directly sequenced. Indel and SNP could be easily resolved by using Indelligent or ShiftDetect program without any reference sequence. However, detection of others genomic variants remains a challenge because of the lack of appropriate tools to analyze heterozygous base-calling fluorescence chromatogram data. In this study, we developed the Mixed Sequence Reader (MSR), a user friendly web-based tool that can directly analyze heterozygous base-calling fluorescence chromatogram data with ABI file format using reference sequence. The heterozygous sequences can be separated as two combination sequences base on the Indelligent method and aligned with reference genomic sequences. MSR provide more information and more application. Include, (1) Indels sequences, base on the NCBI references sequences, MSR can provide the location of the physical position of indels. (2) Microsatellite sequences, MSR can identify the combination haplotype which were defined by microsatellite sequences database, i.e. Federal Bureau of Investigation Combined DNA Index System (CODIS). (3) Dual type virus infection sequences, MSR can detect the genotype the major and minor infection virus with the virus database. i.e. Human Papillomavirus Virus. (4) Paralog gene sequences, MSR can measure the ratio of copy number between two paralog genes, if one of the paralog sequences is a copy number variant (i.e. -defensin 4 genes, DEFB4 and its paralog HSPD5). 目前執行中之計劃 : 1. 國科會 : 研究諾羅病毒於良性嬰兒癲癇之角色及其致病機制第 2 頁, 共 8 頁

3 執行期間 : 至長庚紀念醫院 : 發展一套分析雙倍體 DNA 中混和單倍體序列的程式 : 應用於偵測核酸多型性, 插入或缺失, 及基因上的複製數變異. 執行期間 : 至長庚紀念醫院 : 執行期間 : 至實驗室成員 A. 臨研所博士班 : 1. 郭玟伶 ( 林口長庚一般外科 ) Topic: Establishment of breast mammalian cells and cancer cell lines from Asian women 2. 蔡宏杰 ( 林口長庚腦神精外科 ) Topic: The effect of valproate on outcome of glioblastoma multiforme Published paper: Tsai HC, Wei KC, Tsai CN, Huang YC, Chen PY, Chen SM, Lu YJ, Lee ST. Effect of valproic acid on the outcome of glioblastoma multiforme. 2011, British Journal of Neurosurgery, In press. 畢業生 : 博士班 1. 陳世彥 ( 林口長庚兒童醫院胃腸科, 與邱政洵醫師共同指導 ) published paper: 1. Chen SY, Chang YC, Lee YS, Chao HC, Tsao KC, Lin TY, Ko TY, Tsai CN* and Chiu CH. Molecular Epidemiology and Clinical Manifestations of Viral Gastroenteritis in Hospitalized Pediatric Patients in Northern Taiwan. Journal of clinical microbiology, June 2007, p Chen SY#, Tsai CN#, Chao HC, Lai MW, Lin TY, Ko TY, and Chiu CH*. Acute Gastroenteritis Caused by Multiple Enteric Pathogens in Children in Northern Taiwan, Epidemiology and Infection, 2009 Jul;137(7): (# contribute equally) 3. Chen SY#, Tsai CN#, Lai MW, Chen TY, Lin TY and Chiu CH*. Norovirus is as a causative agent for Benign infantile convulsions, Clinical Infectious Diseases, 2009 Apr 1;48(7):849-55, (# contribute equally) 參與會議論文 : 1. Chen SY, Chang YC, Lee YS, Chao HC, Lin TY, Chiu CH and Tsai CN. Etiology and Clinical Features of Acute Viral Gastroenteritis of Children in Taiwan. 1 st Asian pediatric meeting (Japan, 2004), oral presentation, Traveling award. 2. Chen SY, Chao HC, Lin TY, Chiu CH and Tsai CN. Asian society of pediatric research 4 th (Hawaii, 2008) poster section, Traveling award. 碩士班 1. 楊世維 ( 基隆長庚耳鼻喉科 ) Topic: Molecular Epidemiological Analysis of Human Papillomavirus in Malignant and Premalignant Lesions of Head and Neck Published paper: 1. Yang SW, Lee YS, Chen TA, Wu CJ, and Tsai CN*. Human papillomavirus in oral leukoplakia is no prognostic indicator of malignant transformation. Cancer Epidemiology, (2009), 33: Yang SW*, Wu CJ, Lee YS, Chen TA and Tsai CN. Postoperative Recurrence as an Associated 第 3 頁, 共 8 頁

4 Factor of Malignant Transformation of Oral Dysplastic Leukoplakia, ORL J Otorhinolaryngol Relat Spec Aug 25;72(5): 詹維軒 ( 雙和醫院耳鼻喉科 ) Topic: Study regulation of DLEC1 in head and neck squamous cell carcinoma Published paper: Jan WS, Chang KP, Yang SW, Yao TC, Ko TY, Tsai CL and Tsai CN*. Promoter methylation of DLEC1 is an early event for tumor progression and its down-regulation level is associated with the depth of tumor invasion in oral squamous cell carcinoma, oral oncology, 2010, 46: 周怡君 ( 署立桃園醫院小兒科 ) Topic: Association of single nucleotide polymorphism in beta2-adrenergic and beta3-adrenergic receptor gene with adolescent obesity in Taiwanese. Published paper: Chou YC, Tsai CN, Lee YS, and Pei JS* The association of -2 and -3 adrenergic receptor genes polymorphisms with adolescent obesity in Taiwan, pediatric international journal, 2012 Feb;54(1): 張伯宏 ( 林口長庚耳鼻喉科 ) Topic: Study regulation of DLEC1 in sinonasal inverted papilloma and squamous cell carcinomas Published paper: 1. Huang CC, Lee TJ*, Chang PH, Lee YS, Chuang CC, Jhang YJ, Chen YW, Chen CW, Tsai CN*. Desmoglein 3 is overexpressed in inverted papilloma and squamous cell carcinoma of sinonasal cavity, Laryngoscope, 2010, 120(1): Huang CC, Lee TJ, Chang PH, Lee YS, Chuang CC, Jhang YJ, Chen YW, Chen CW, Fu CH and Tsai CN* Expression of cathepsin S and its inhibitor stefin A in sinonasal inverted papilloma, Rhinology International Journal, 2010, 48(3): Wu CC, Lee TJ, Chang PH, Tsai CN, Lee YS, Fu CH and Huang CC. Similar cellular proliferation activities in nasal polyps and adjacent inferior turbinate, American Journal of Otolaryngology, 2012 Jan;33(1): Chang PH, Huang CC, Lee TJ, Jhang YJ, Lai YC, Lee YS, and Tsai CN*. Down-regulation of a functional tumor suppression gene, DLEC1, in sinonasal inverted papilloma and squamous cell carcinoma, 2012, Journal of Otolaryngology-Head & Neck Surgery, In press 四專業證照 ( 請填所有曾取得之專業證照, 其中起訖年月請以民國. 月份表示 ) 專業證照專業證照與教學之配合情形取得日期放射性物質可發生游離輻射設備操作職照可以操作非密封放射性物質及相關需操作放射性的基礎實驗 1996/05/09 五教授課程 ( 一 ) 任教課程 ( 請填所有可教授之課程 ) 開設於本所之課程基因調控, 基礎基因體學, 腫瘤生物學, 生物醫學技術, 現代生物技術, 微生物致病基制, 博碩士班專題討論第 4 頁, 共 8 頁

5 可支援其他系所之課程教師專長與教學科目配合度學術經驗與教學研究配合度 Yeast two-hybrid; Virology; Molecular biology, Cell biology, 儀器分析法及實驗, 專題討論本所學生都是在職的臨床醫師, 對於掌握基礎醫學的知識與技術較為陌生, 而且缺乏設計基礎實驗嘗試解決問題的能力而本人下學期開始負責微生物致病機轉, 基因調控特論, 及基礎基因體醫學, 課程內容以現行期刊為主, 同時在課堂中加入現行新的技術的應用, 讓這些臨床醫師了解到, 國外的研究學者如何結合臨床的發現及深入探討基礎醫學研究的方式! 藉此訓練培養其從事基礎研究的能力在本人在過去幾年中不只積極參與研究工作, 同時也學會如何引導學生思考, 因此過去的教學中學生反應良好, 本人將秉持著與學生互動的方式繼續教學同時將積極參與研究工作. 研究 ( 二 ) 近五年論文專書專文專利發表明細 ( 請務必註明 SCI, EI 等 ) 論文 :( 請依期刊 / 會議分列, 並註明屬 SCI/EI/ 等等, 受引用次數 ) 期刊論文 :(*corresponding author, #equal contribution) (2012) 1. Wu CC, Lee TJ, Chang PH, Tsai CN, Lee YS, Fu CH and Huang CC. Similar cellular proliferation activities in nasal polyps and adjacent inferior turbinate, American Journal of Otolaryngology, 2012 Jan;33(1): Chou YC, Tsai CN, Lee YS, and Pei JS* The association of -2 and -3 adrenergic receptor genes polymorphisms with adolescent obesity in Taiwan, Pediatric International, 2012 Feb;54(1): Chao A, Lin CY, Lee YS, Tsai CL, Wei PC, Hsueh S, Wu TI, Tsai CN, Wang CJ, Chao AS, Wang TH, Lai CH. Regulation of ovarian cancer progression by microrna-187 through targeting Disabled homolog-2. Oncogene. 2012, Feb 9;31(6): Yu MC, Kuo WL, Lee JF, Tsai CN, Chen TC, Chen MF* Imatinib Mesylate Improves Liver Regeneration and Attenuates Liver Fibrogenesis in CCL4-treated Mice, J Gastrointest Surg Feb;16(2): Epub 2011 Nov Tsai HC, Wei KC, Tsai CN, Huang YC, Chen PY, Chen SM, Lu YJ, Lee ST. Effect of valproic acid on the outcome of glioblastoma multiforme. British Journal of Neurosurgery, 2012 Jun;26(3): Epub 2011 Dec Lu YC, Wang HM, Tsai CY, Chen WH, Huang YC, Fan HK, Tsai CN, Huang SF, Kang CJ, Chang J and Cheng AJ*. Oncogenic function and early detection potential of mirna-10b in oral cancer as identified by microrna profiling, Cancer Prev Res. 2012, 5(4): Chang PH, Huang CC, Lee TJ, Lee YS and Tsai CN*. Down-regulation of DLEC1 in sinonasal inverted papilloma and squamous cell carcinoma. Journal of Otolaryngology -Head & Neck Surgery, 2012 Jan;33(1): Chan CK, Wu KH, Lee YS, Hwang SM, Laio SK, Cheng EH, See LC, Tsai CN, Kuo ML, and Huang JL. The Comparison of Interleukin-6 Associated Immunosuppressive Effects of Human ESCs, Fetal-Type MSCs, and Adult-Type MSCs. Transplantation, 2012, 94(2): Yu TH, Tsai CN, Lai MW, Chen CC, Chao HC, Chiu CH and Chen SY* Antigenemia and Cytokine Expression in Rotavirus Gastroenteritis in Children, Journal of Microbiology, Immunology and Infectious, 2012 Aug;45(4): Equb 2011 Dec 12. 第 5 頁, 共 8 頁

6 10. Chang CT#, Tsai CN#, Tang CY, Chen CH, Lian JH, Hu CY, Tsai CL, Chao A, Lai CH, Wang TH* and Lee YS*. Mixed Sequence Reader (MSR) for Analyzing DNA sequences with heterozygous base calling chromatography to detect genomic variations with a reference database. The Scientific World Journal, 2012;2012: Epub 2012 Jun Shei WL, Lin YK, Tsai CN, Wang TM, Chen TY, Pang JH. Indirubin, the acting component of indigo naturalis, inhibits EGFR activation and EGF-induced CDC25B gene expression in epidermal keratinocytes. Journal of Dermatological Science Aug;67(2): Equb 2012 Jun Tsai CL, Tsai CN, Lin CY, Chen HW, Lee YS, Chao A, Wang TH*, Wang HS, Lai CH. Secreted stress-induced phosphoprotein 1 activates the ALK2-SMAD signaling pathways and promotes cell proliferation of ovarian cancer cells. Cell Repots, 2012, Aug 30;2(2): Yu MC, Lee YS, Lin SE, Wu HY, Chen TC, Lee WC, Chen MF*, and Tsai CN* Recurrence and Poor Prognosis following Resection of Small Hepatitis B-Related Hepatocellular Carcinoma Lesions are Associated with Aberrant Tumor Expression Profiles of Glypican 3 and Osteopontin. Annals of surgical oncology, 2012 Jul;19 Suppl 3: (2011) 14. Yang SW*, Tsai CN, Lee YS, Chen TA. Treatment outcome of dysplastic oral leukoplakia with carbon dioxide laser - Emphasis on the factors affecting recurrence. Journal of Oral and Maxillofacial Surgery, 2011 Jun;69(6):e78-87 (2010) 15. Chan WH, Chang KP, Yang SW, Yao TC, Ko TY, Lee YS, Tsai CL and Tsai CN*. Transcriptional repression of DLEC1 associates with the depth of tumor invasion in oral squamous cell carcinoma. Oral oncology, 2010, 46: Yang SW*, Wu CJ, Lee YS, Chen TA and Tsai CN. Postoperative Recurrence as an Associated Factor of Malignant Transformation of Oral Dysplastic Leukoplakia, ORL J Otorhinolaryngol Relat Spec Aug 25;72(5): Chang KP; Kao HK; Liang Y; Cheng MC; Liu SC; Lin YC; Lee YS; Tsai CL; Hao SP; Tsai CN* Overexpression of activin A is associated with poor prognosis in patients with oral squamous cell carcinoma and promotes the proliferation, motility and invasion of oral cancer cells, Annals of Surgical Oncology, 2010 Jul;17(7): Huang CC, Lee TJ, Chang PH, Lee YS, Chuang CC, Jhang YJ, Chen YW, Chen CW, Fu CH and Tsai CN* Expression of cathepsin S and its inhibitor stefin A in sinonasal inverted papilloma, 2010, Rhinology International Journal, 48(3): Huang CC, Lee TJ*, Chang PH, Lee YS, Chuang CC, Jhang YJ, Chen YW, Chen CW, Tsai CN* Desmoglein 3 is overexpressed in inverted papilloma and squamous cell carcinoma of sinonasal cavity, Laryngoscope, 2010 Jan;120(1): Shiue, HS, Lee YS, Tsai CN, Hsueh YM, Sheu JR, Chang HH * Gene expression profile of Phadiatop positive and negative Allergic Rhinitis Patients treated with Acupuncture, Journal of Alternative and Complementary Medicine 2010, Volume 16( 2): Chao A#, Tsai CL#, Wei PC, Hsueh S, Chao AS, Wang CJ, Tsai CN, Lee YS, Wang TH, Lai CH. Decreased expression of microrna-199b increases protein levels of SET (phosphatase 2A inhibitor) in human choriocarcinoma. Cancer letter, 2010, 291: (2009) 22. Chen SY#, Tsai CN#, Chao HC, Lai MW, Lin TY, Ko TY, and Chiu CH*. Acute Gastroenteritis Caused by Multiple Enteric Pathogens in Children in Northern Taiwan, Epidemiology and Infection, 2009 Jul;137(7): Yang SW, Lee YS, Chen TA, Wu CJ, and Tsai CN*. Human papillomavirus in oral 第 6 頁, 共 8 頁

7 leukoplakia is no prognostic indicator of malignant transformation. Cancer Epidemiology 2009, 33: Chao A #, Tsai CN #, Hsueh S, Chen TC, Huang SL, Lee LY, Chao FY and CH Lai*. Does Epstein-Barr virus play a role in lymphoepithelioma-like carcinoma of the uterine cervix? International Journal of Gynecological Pathology, 2009, 28(3): (# contributes equally) 25. Lee YS, Chen CH, Tsai CN, Tsai CL, Chao A*, and Wang TH*. Microarray Labeling Extension Values: Laboratory Signatures for Affymetrix GeneChips. Nucleic Acid Research, 2009 May;37(8):e Chen SY#, Tsai CN#, Lai MW, Chen TY, Lin TY and Chiu CH*. Norovirus is as a causative agent for Benign infantile convulsions, Clinical Infectious Diseases, 2009 Apr 1;48(7):849-55, (# contribute equally) (2008) 27. Shiue HS, Lee YS, Tsai CN, Hsueh YM, Sheu JR and Chang HH*. DNA Microarray Analysis of Inflammation Effect in Patients of Allergic Rhinitis Treated with Acupuncture, Journal of Alternative and Complementary Medicine, 2008, 14(6): Lee YS, Tsai CN, Tsai CL, ChangSD, Hsueh DW, Liu JT, Ma CT, Lin SH, Wang TH* and Wang HS. Comparison of whole genome amplification methods for further quantitative analysis with microarray-based comparative genomic hybridization. Taiwanese Journal of Obstetrics & Gynecology, 2008, 47(1): Chou A, Wang TH, Lee YS, Hong JH, Tsai CN, Chen CK, Chao AS, and Lai CH* Changes of gene expression profiles in the peripheral blood of patients with cervical cancer undergoing concurrent chemoradiation: A pilot study. Radiation Research, 2008, 169(1): Chang KP, Ho SP, Tsang NM, Chang YL, Cheng MH, Liu CT, Lee YS, Tsai CL, Lee TJ, Wang TH, and Tsai CN* Gene Expression and Promoter Polymorphisms of DNMT3B in Nasopharyngeal Carcinomas in Taiwanese people: A Case-Control Study. Oncology reports 2008, 19: (2007) 31. Chen SY, Chang YC, Lee YS, Chao HC, Lin TY, Ko TY, Tsai CN* and Chiu CH* Etiology and Clinical Features of Acute Viral Gastroenteritis of Children in Taiwan, 2004~ Journal of Clinical Microbiology 2007, 45: Chang KP, Ho SP, Liu CT, Cheng MH, Chang YL, Lee YS, Wang TH, and Tsai CN* DNMT3B polymorphisms in risk of Head and Neck Squamous Cell Carcinoma (HNSCC) in Taiwan: a case-control study. Oral Oncology 2007, 43(4): (2006) 33. Wu CC, Tsai CN., Kuo TT, Wong WR, Hong HS and Chuang YH*. Early congenital syphilis presenting as erythema multiforme-like targetoid lesions in a one-day-old male newborn and detection of Treponema pallidum genomic DNA using nested polymerase chain reaction. Journal of the American Academy of Dermatology, 2006, Aug;55(2 Suppl):S11-5. (Before 2002) 34. Tsai CN, Tsai CL, Tse KP, Chang HY, and Chang YS*. The Epstein-Barr virus oncogene product, Latent Membrane Protein 1, induces the down-regulation of E-cadherin gene expression via activation of DNA methyltransferases Proc Natl Acad Sci, USA 99: Liang CL, Tsai CN, Chung PJ, Chen JL, Sun CM, Chen RH, Hong JH, Chang YS*. Transcription of Epstein-Barr virus-encoded nuclear antigen 1 promoter Qp is 第 7 頁, 共 8 頁

8 repressed by transforming growth factor-beta via Smad4 binding element in human BL cells. Virology 2000 Nov 10;277(1): Tsai CN, Lee CM, Chien CK, Kuo SC, Chang YS*. Additive effect of Sp1 and Sp3 in regulation of the ED-L1E promoter of the EBV LMP 1 gene in human epithelial cells. Virology 1999 Sep 1;261(2): Tsai CN, Liu ST, Chang YS*. Identification of a novel promoter located within the Bam HI Q region of the Epstein-Barr virus genome for the EBNA 1 gene. DNA Cell Biol 1995 Sep;14(9): Chang YS, Lin YJ, Tsai CN, Shu CH, Tsai MS, Choo KB, Liu ST. Detection of mutations in the p53 gene in human head and neck carcinomas by single strand conformation polymorphism analysis. Eds T. Tursz, JS Pagano, DV Ablashi, G. de The G. Lenoir, GR Person. The Epstein-Barr virus and Association Diseases. Colloque INSERM/John Libbery Eurotext Ltd. 1993, Vol:225, pp Chang YS, Lin YJ, Tsai CN, Shu CH, Tsai MS, Choo KB, Liu ST. Detection of mutations in the p53 gene in human head and neck carcinomas by single strand conformation polymorphism analysis. Cancer Lett 1992 Dec 24;67(2-3): Chen ML, Tsai CN, Liang CL, Shu CH, Huang CR, Sulitzeanu D, Liu ST, Chang YS. Cloning and characterization of the latent membrane protein (LMP) of a specific Epstein-Barr virus variant derived from the nasopharyngeal carcinoma in the Taiwanese population. Oncogene 1992 Nov;7(11): 第 8 頁, 共 8 頁

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<4D6963726F736F667420576F7264202D20ECFAD0C0D0C0C2DBCEC4CCE1BDBB6F7665722E646F63> 硕士专业学位论文论文题目鲍温病临床病理特征和几种治疗方法比较的分析研究研究生姓名指导教师姓名禚欣欣康定华专业名称皮肤性病学研究方向皮肤肿瘤与皮肤病理论文提交日期 2013 年 4 月 I 鲍温病临床病理特征和几种治疗