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姓名:吳漢忠

職稱:研究員 兼代理所長

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專長:Molecular Biology,
Cell Biology

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研究人員 / 簡介

2010-01-, Research Fellow, Institute of Cellular and Organismic Biology, Academia Sinica
2010-02-, Professor, Institute of Pathology and Graduate Institute of Oral Biology, National Taiwan University
2010-01-, Joint Appointment Research Fellow, Genomics Research Center, Academia Sinica
2005-2009, Associate Research Fellow, Institute of Cellular and Organismic Biology, Academia Sinica
2001-2005, Assistant & Associate Professor, Institute of Pathology, National Taiwan University
2001-2005, Assistant & Associate Professor, Graduate Institute of Oral Biology, National Taiwan University
1996-2001, Assistant & Associate Research Fellow, Institute of Preventive Medicine, National Defense Medical Center
1993, Ph.D. Institute of Pathology, National Taiwan University, Taiwan

吳漢忠 老師 實驗室

  • 癌症之標的蛋白及標的治療研究與影像研究      

    癌症是人類最常見的死因之一,全世界每年的死亡人數已經超過八百萬人。而化學療法易產生抗藥性,是治療癌症失敗的主因。化學療法為了避免抗癌藥物造成正常組織毒性而產生的副作用,常常只能給予次適當濃度的抗癌藥物劑量,因此伴隨著抗藥性以及癌細胞轉移的發生,終究造成治療的失敗。因此,標靶藥物傳輸系統能夠減低藥物的副作用,增加抗癌療效,有希望發展成為新的癌症療法。近年來,本實驗室為了解決此問題,發展出一套噬菌體顯現法(Phage display)來尋找癌細胞、腫瘤幹細胞或腫瘤血管上的特殊表現受體。我們已經利用噬菌體顯現法技術,成功建構人類天然(naïve)抗體庫,包含六百億株以上的人類抗體(6 ´ 1010),搭配多種親和力淘選方法,進行專一性抗體篩選,可作為快速與精準找到癌症抗體新藥的平台。

       利用噬菌體顯現法胜肽庫與抗體庫的方法,我們已經尋獲許多能導向癌細胞、腫瘤血管、醣抗原與特殊受體之標的胜肽與人類抗體。為了進一步發展標的治療,我們將標的配體接合微脂體抗癌藥物,用以治療移殖人類腫瘤的免疫不全鼠。具有標的配體功能的帶藥微脂體能更有效的抑制腫瘤生長,顯示較佳的治療效果,以及無明顯副作用等優點,未來具有臨床潛力運用在癌症的標的治療、以及設計標的基因轉換載體等。 並且,我們將標的胜肽或抗體接合至量子點或超順磁氧化鐵奈米粒子,進行活體腫瘤造影分析。運用螢光或MRI系統分析,我們發現標的胜肽可更為精準、有效率的將顯影試劑運送至腫瘤組織而加強成像,在未來可幫助癌症的診斷與早期偵測。

       進一步我們可將篩選出的抗體片段,運用蛋白質工程的技術改造成全人類抗體,研究其功能。若有需要,可利用親和力成熟化技術提升抗體結合強度,將更有助治療性抗體之開發。此一系列創新的研究成果已陸續獲得16項國內外專利,其中10項專利已授權給生技公司,進行藥物或診斷試劑之研發。

       另一方面,我們鑑定這些胜肽及抗體所結合之標的蛋白,探討這些蛋白的功能及研究其在細胞內的訊號傳遞機制。

     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
     
    登革病毒研究
       登革病毒感染,會引起登革熱,嚴重則引起登革出血性熱以及登革休克症候群。每年約有三億九千萬到的登革熱病例
    產生,其中有二十五至五十萬人會引起出血性登革熱。約有40%地球的人口生活在可能被感染的危險區域。目前尚無抗原(蛋白或胜肽)可以專一性分辨四型登革病毒的感染,也無有效且安全的疫苗及專一性治療性抗體。對於登革出血熱的致病機轉,是經由不同型登革病毒交叉感染,或是病毒及宿主間一次感染的交互作用,還是病毒感染後所產生的免疫病理反應,至今仍尚未定論。為了要解決這些問題,本實驗室已建立了許多對抗四型登革病毒之單株抗體,藉由研究這些抗體的B細胞抗原決定位(epitopes),來了解登革病毒(1)專一性及中和性的抗原決定位(JGV 2003; Clin Vaccine Immunol 2007; PLoS NTD 2012; Adv Health Mat 2014),(2)保護性及致病性抗原決定位之位置(JV 2008; JBC 2011; PLoS NTD; 2015; PLoS One 2015),進一步釐清登革出血熱之致病機轉,用以研發有效且安全之登革疫苗(PLoS NTD, 2015)、治療性抗體(包括擬人化抗體及全人類抗體)及偵檢試劑。
     
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    吳漢忠研究員
  • 著作目錄

    1.  Lin, C.W., Liao, M.Y., Lin, W.W., Wang, Y.P., Lu, T.Y., and Wu, H. C.* (2012). Epithelial Cell Adhesion Molecule Regulates Tumor Initiation and Tumorigenesis via Activating Reprogramming Factors and Epithelial-Mesenchymal Transition Genes Expression in Colon Cancer. Journal of Biological Chemistry 287, 39449-39459.
    2.  Li, P.C., Liao, M.Y., Cheng, P.C., Liang, J.J., Liu, I.J., Chiu, C.Y., Lin, Y.L., Chang, G.J. J., and Wu, H.C.* (2012). Development of a Humanized Antibody with High Therapeutic Potential against Dengue Virus Type 2. PLoS Negl Trop Dis, 6, e1636.
    3.  Tung, K.H., Lin, C.W., Kuo, C.C., Li, L.T., Kuo, Y.H., Lin, C.W., and Wu, H. C.* (2013). CHC promotes tumor growth and angiogenesis through regulation of HIF-1a and VEGF signaling. Cancer Letters 331, 58-67.
    4.  Lu, R. M., Chen, M. S., Chang, D. K., Chiu C. Y., Lin, W. C., Yan, S. L., Wang, Y. P., Kuo, Y. S., Lo, A., and Wu, H. C.* (2013). Targeted drug delivery systems mediated by a novel peptide in breast cancer therapy and imaging. PLoS ONE 8, e66128.
    5. Wu, J. C., Tseng, P. Y., Tsai, W. S., Liao, M. Y., Lu, S. H., Frank, C. W., Chen, J. S. Wu, H. C.*, and Chang, Y. C.* (2013). Antibody Conjugated Supported Lipid Bilayer for Capturing and Purification of Viable Tumor Cells in Blood for Subsequent Cell Culture. Biomaterials 34, 5191-5199.
    6. Wang, Y. P., Liu, I. J., Chiang, C. P., and Wu, H. C.* (2013). Astrocyte elevated gene-1 is associated with metastasis in head and neck squamous cell carcinoma through p65 phosphorylation and upregulation of MMP1. Molecular Cancer 12, 109.
    7. Chang, D. K., Li, P. C., Lu, R. M., Jane, W. N., and Wu, H. C.* (2013). Peptide-mediated liposomal doxorubicin enhances drug delivery efficiency and therapeutic efficacy in animal models. PLOS ONE 8, e83239.
    8. Lin, C. W., Sun, M. S. and Wu, H. C.* (2014). Podocalyxin-like 1 is associated with tumor aggressiveness and metastatic gene expression in human oral squamous cell carcinoma. International Journal of Oncology 45, 710-718.
    9. Lin, C. W., Sun, M. S., Liao, M. Y., Chung, C. H., Chi, Y. H., Chiou, L. T., Yu, J., Lou, K. L., and Wu, H. C.* (2014). Podocalyxin-like 1 promotes invadopodia formation and metastasis through activation of Rac1/Cdc42/Cortactin signaling in breast cancer cells. Carcinogenesis 35, 2425-2435.
    10. Liao, M. Y., Kuo, M. Y. P., Lu, T. Y., Wang, Y. P., Wu, H. C.* (2015). Generation of an anti-EpCAM antibody and epigenetic regulation of EpCAM in colorectal cancer. International Journal of Oncology 46, 1788-1800.
    11. Shen, Y. A., Liu, C. S., Chang, Y. H., Chen, P. H., He, C. L., Wu, H. C.* and Chuang, C. M.* (2015). Subtype-specific binding peptides enhance therapeutic efficacy of nanomedicine in the treatment of ovarian cancer. Cancer Letters 360, 39-47.
    12. Hsiao, J. K., Wu, H. C.*, Liau, H. M., A. Yu, Lin, C. T.* (2015). A multifunctional peptide for targeted imaging and chemotherapy for nasopharyngeal and breast cancers. Nanomedicine: NBM 11, 1425–1434.
    13. Tang, C. T., Liao, M. Y., Chiu, C. Y., Shen, W. F., Chiu, C. Y., Cheng, P. C., Chang, G. J. J., Wu, H. C.* (2015). Generation of monoclonal antibodies against dengue virus type 4 and identification of enhancing epitopes on envelope protein. PLoS ONE 10(8): e0136328.
    14. Tang, C. T., Li, P. C., Liu, I. J., Liao, M. Y., Chiu, C. Y., Chao, D. Y., Wu, H. C.* (2015). An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2. PLoS Negl Trop Dis 9(7): e0003903.
    15. Tang, Y. L., Chiu, C. Y., Lin, C. Y., Huang, C. H., Chen, Y. H., Destura, R. V., Chao, D. Y., Wu, H. C.* (2015). Establishment and comparison of two different diagnostic platforms for detection of DENV1 NS1 protein. International Journal of Molecular Sciences. 16, 27850-27864,
    16. Liao, M. Y., Lai, J. K., Kuo, M. Y. P., Lu, R., Lin, C. W., Cheng, P. C., Liang, K. H., Wu, H. C.* (2015). An anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer. Oncotarget 6, 24947-24968.
    17. Wu, C. H., Kuo, Y. H., Hong, R. L., Wu, H. C.* (2015). α-Enolase-Binding Peptide Enhances Drug Delivery Efficiency and Therapeutic Efficacy Against Colorectal Cancer. Science Translational Medicine 7, 290ra91, 1-14.
    18. Wu, C. H., Liu, I. J., Lu, R. M., Wu, H. C. * (2016). Advancement and applications of peptide phage display technology in biomedical science. Journal of Biomedical Science. 23, 8. (Invited review article)
    19. Yeh, C. Y., Hsiao, J. K., Wang, Y. P., Lan, C. H. and Wu, H. C.* (2016). Peptide-conjugated nanoparticles for targeted imaging and therapy of prostate cancer. Biomaterials 99, 1-15.
    20. Kuan, I. I., Liang, K. H., Wang, Y. P., Kuo, T. W., Meir, Y. J. J., Wu, S. C. Y., Lu, J., and Wu, H. C.* (2017). EpEX/EpCAM and Oct4 or KLF4 alone are sufficient to generate induced pluripotent stem cells through STAT3 and HIF2a. Scientific Reports 7: 41852.
    21. Chi, Y. H., Hsiao, J. K., Lin, M. H., Chang, C., Lan, C. H. and Wu, H. C.* (2017). Lung cancer-targeting peptides with multi-subtype indication for combinatorial drug delivery and molecular imaging. Theranostics 7, 1612-1632.
     

    *Corresponding author

     

     

     

     

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    115台北市南港區研究院路二段128號
    Tel: 02-27899515
    Fax: 02-27858059
    icob@gate.sinica.edu.tw
    Copyright © ICOB 2013. All rights reserved. 最佳瀏覽網頁方式請用最新版IE11或其他瀏覽器 /瀏覽人數:969117--
     瀏覽人數:969117