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徐志文 博士
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    轉譯醫學研究室 副研究員 
    徐志文(Chih-Wen Shu)

    學術經歷:

    1. Associate research fellow in Kaohsiung Veterans General Hospital, Taiwan (2014-present)
    2. Associate professor, Ministry of Education, Taiwan.  (2015)
    3. Adjunct associate professor in Tajen University, Taiwan (2015)
    4. Adjunct assistant professor in Tajen University, Taiwan (2014)
    5. Senior assistant research fellow in Kaohsiung Veterans General Hospital, Taiwan (2011-2014)
    6. Research Fellow, The SASS Foundation for Medical Research, Inc., Roslyn, NY, USA. (2009-2011) 
    7. Postdoctoral Fellow, HTS Screening Center, Sanford-Burnham Medical Research Institute, USA (2007-2011)
    8. Visiting Researcher, Moores Cancer Center, University of California, San Diego, USA. (2005-2007)

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    學歷:

    Ph.D., Department of Life Science, National Tsing Hua University, Taiwan.  (2001-2007)

    1. Cancer biology
    2. Signal transduction
    3. Autophagy
    4. Assays and biomarkers development
    5. Functional genomics and chemical screening
    6. Drug discovery
    1. Excellent Paper Award, Kaohsiung Veterans General Hospital, Taiwan (2014, 2015)
    2. Editor, Journal of Biological Methods, USA (2014-present)
    3. Reviewer of many journals (2014-present)
    4. Outstanding Paper Award, Kaohsiung Veterans General Hospital, Taiwan (2014)
    5. Postdoctoral Fellowship awarded, The SASS Foundation for Medical Research, Inc., Roslyn, NY, USA. (2009-2011)
    6. Graduate student scholarship, National Science Council, Taiwan. (2007)

    My personal research interests are on I) functional genomics screening for  new biomarkers/drug targets in certain types of cancer, II) develop or screen suitable inhibitor for drug targets as I), III, a) Determine the role of autophagy in diseases, particular in cancer and infectious diseases, and b) high throughput screening for modulators of ATG4 (key protease in autophagy).

    Autophagy could be beneficial and detrimental in different diseases or treatments.  The role of autophagy in diseases remains unclear, particular in clinical setting.   We will develop autophagic sensors and examine protein levels of several autophagic markers to determine the role of autophagy in patients.  Moreover, we have kinome siRNA library (710 kinase related genes) in house, which allow us to address the regulation of kinase on ATG4 in cancer cells, screen suitable biomarkers/drug targets for cancer therapy.  By siRNA library screening, we would find new oncogenes that master the tumorigenesis pathways in cancer cells.  The expression of these oncogenes/drug targets and downstream effectors will be examined with tissue microarray (TMA).  Based on developed drug targets, we also have FDA approved drug library (640 drugs) to screen known drugs potentially inhibits the drug targets.  We will employee the inhibitors or modified antisense oligonucleotide or monoclonal antibody (for surfaced targets) to inhibit the oncotargets, which would be applicable in the clinical setting

     

    SELECTED (* corresponding author )

     

    1. Tsai KL; Hsu CJ; Tsai WL; Cheng JS; Chang HW; Shiau CW; Goan YG; Tseng HH; Wu CH; Reed JC; Yang LW; Shu CW*.  An ATG4 Inhibitor that Suppresses Autophagy and Sensitizes Cancer Cells to Chemotherapy. Theranostics. 2017 accepted. (IF: 8.76, SCI, 8/128, MEDICINE, RESEARCH & EXPERIMENTAL)

    2. Liu PF; Hsu CJ; Tsai WL; Cheng JS; Chen JJ; Huang IF; Tseng HH; Chang HW; Shu CW*. Ablation of ATG4B suppressed autophagy and activated AMPK for cell cycle arrest in cancer cells. Cell Physiol Biochem. 2017 44:728-740. (IF:5.1, SCI, 6/84, PHYSIOLOGY).
    3. Hu YC,  Kang BH, Tseng YK, Wu PC, Liang CC, Hou YY, Fu TY, Liou HH, Hsieh IC, Ger LP, Shu CW*. Expression levels of cleaved caspase-3 and caspase-3 in tumorigenesis and prognosis of oral tongue squamous cell carcinoma. PLoS One.2017 Jul 10;12(7):e0180620. (IF: 2.806, SCI, 11/63, MULTIDISCIPLINARY SCIENCES).
    4. Yen CY, Huang HW, Shu CW, Hou MF, Yuan SF, Wang HR, Chang YT, Farooqi AA, Tang JY, Chang HW. DNA methylation, histone acetylation and methylation of epigenetic modifications as a therapeutic approach for cancers. Cancer Lett. 2016 Jan 22. pii: S0304-3835(16)30006-4. (IF: 6.37, 24/211, ONCOLOGY)
    5. Sheu SJ, Chen JL, Bee YS, Chen YA, Lin SH, Shu CW*  Differential autophagic effects of vital dyes in retinal pigment epithelial ARPE-19 and photoreceptor 661W cells. PLoS One. 2017 Mar 30;12(3):e0174736. (IF:3.535, SCI, 11/63, MULTIDISCIPLINARY SCIENCES).
    6. Shu CW, Chang HT, Wu CS, Chen CH, Wu S, Chang HW, Kuo SY, Fu E, Liu PF, Hsieh YD. RelA-Mediated BECN1 Expression Is Required for Reactive Oxygen Species-Induced Autophagy in Oral Cancer Cells Exposed to Low-Power Laser Irradiation.. Plos One, 2016 11(9):e0160586. (IF:3.535, SCI, 11/63, MULTIDISCIPLINARY SCIENCES).

    7. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ.... Shu CW….et al., Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016 Jan 2;12(1):1-222. (IF: 11.753, 15/185, CELL BIOLOGY)

    8. Huang IF, Lin IC, Liu PF, Cheng MF, Liu YC, Hsieh YD, Chen JJ, Chen CL, Chang HW, Shu CW*. Lactobacillus acidophilus attenuates Salmonella-induced intestinalinflammation via TGF-β signaling. BMC Microbiol. 2015 Oct 7;15(1):203. doi:10.1186/s12866-015-0546-x. (IF: 3.251, 51/119, MICROBIOLOGY)

    9. Liang WZ, Liu PF, Fu E, Chung HS, Jan CR, Wu CH, Shu CW*, Hsieh YD. Selective cytotoxic effects of low-power laser irradiation on human oral cancer cells. Lasers Surg Med. 2015 Nov;47(9):756-64. doi: 10.1002/lsm.22419. (IF: 3.066, 49/198, SURGERY)

    10. Liu PF, Hsieh YD, Lin YC, Two A, Shu CW*, Huang CM. Propionibacterium acnes in the Pathogenesis and Immunotherapy of Acne Vulgaris. Curr Drug Metab. 2015;16(4):245-54. (IF: 2.976, 82/255, PHARMACOLOGY & PHARMACY)

    11. Liu PF, Cheng JS, Sy CL, Huang WC, Yang HC, Gallo RL, Huang CM, Shu CW*. IsaB Inhibits Autophagic Flux to Promote Host Transmission of Methicillin-Resistant Staphylococcus Aureus. J Invest Dermatol. 2015 Nov;135(11):2714-22. doi: 10.1038/jid.2015.254. (IF: 7.216, 1/62, DERMATOLOGY)

    12. Liu PF, Leung CM, Chang YS,Cheng JS, Chen JJ, Weng CJ, Tsai KW, Hsu CJ, Liu YC, Hsu PC, Pan HW, Shu CW*. ATG4B promotes colorectal cancer growth independent of autophagic flux. Autophagy. 2014 Aug;10(8):1454-65. doi: 10.4161/auto.29556. (IF: 11.753, 15/185, CELL BIOLOGY)

    13. Liu PF, Huang IF, Shu CW*, Huang CM. Halitosis vaccines targeting FomA, a biofilm-bridging protein of fusobacteria nucleatum. Curr Mol Med. 2013 Sep;13(8):1358-67. Review. PubMed PMID: 23865430. (IF: 4.197, 27/121, MEDICINE, RESEARCH & EXPERIMENTAL). 

    14. Shu CW, Madiraju C, Zhai D, Welsh K, Diaz P, Sergienko E, Sano R, Reed JC. High-throughput fluorescence assay for small-molecule inhibitors of autophagins/Atg4. J Biomol Screen. 2011 Feb;16(2):174-82. doi: 10.1177/1087057110392996. (IF: 2.423, 37/76, CHEMISTRY, ANALYTICAL).

    15. Shu CW, Drag M, Bekes M, Zhai D, Salvesen GS, Reed JC. Synthetic substrates for measuring activity of autophagy proteases: autophagins (Atg4). Autophagy. 2010 Oct;6(7):936-47. doi: 10.4161/auto.6.7.13075. Epub 2010 Oct 19. (IF: 11.753, 12/185,CELL BIOLOGY).  

    16. Kim I, Shu CW, Xu W, Shiau CW, Grant D, Vasile S, Cosford ND, Reed JC. Chemical biology investigation of cell death pathways activated by endoplasmic reticulum stress reveals cytoprotective modulators of ASK1. J Biol Chem. 2009 Jan 16;284(3):1593-603. doi: 10.1074/jbc.M807308200. Epub 2008 Nov 12. (IF: 4.651, 62/290, BIOCHEMISTRY & MOLECULAR BIOLOGY ).  

    17. Shu CW, Sun FC, Cho JH, Lin CC, Liu PF, Chen PY, Chang MD, Fu HW, Lai YK. GRP78 and Raf-1 cooperatively confer resistance to endoplasmic reticulum stress-induced apoptosis. J Cell Physiol. 2008 Jun;215(3):627-35. PubMed PMID: 18064632. J. Cell. Physiol., 215(3):627-35. (IF: 4.218, 13/83,PHYSIOLOGY).

    18. Kim U, Shu CW, Dane KY, Daugherty PS, Wang JY, Soh HT. Selection of mammalian cells based on their cell-cycle phase using dielectrophoresis. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20708-12. Epub 2007 Dec 19(IF: 9.737, 4/56,MULTIDISCIPLINARY SCIENCES).

    19. Preyer M, Shu CW, Wang JY. Delayed activation of Bax by DNA damage in embryonic stem cells with knock-in mutations of the Abl nuclear localization signals. Cell Death Differ. 2007 Jun;14(6):1139-48. Epub 2007 Mar 16. (IF: 8.371, 26/290,BIOCHEMISTRY & MOLECULAR BIOLOGY).

    20. Shu CW, Cheng NL, Chang WM, Tseng TL, Lai YK. Transactivation of hsp70-1/2 in geldanamycin-treated human non-small cell lung cancer H460 cells: involvement of intracellular calcium and protein kinase C. J Cell Biochem. 2005 Apr 15;94(6):1199-209. (IF: 3.062, 125/290,BIOCHEMISTRY & MOLECULAR BIOLOGY).

    THE OTHERs ( * corresponding author )

    1. Huang JS, Yang CM, Wang JS, Liou HH, Hsieh IC, Li GC, Huang SJ, Shu CW, Fu TY, Lin YC, Ger LP, Liu PF. Caspase-3 expression in tumorigenesis and prognosis of buccal mucosa squamous cell carcinoma. Oncotarget. 2017 Aug 24;8(48):84237-84247.
    2. Farooqi AA, Shu CW, Huang HW, Wang HR, Chang YT, Fayyaz S, Yuan SF, Tang JY,Chang HW. TRAIL, Wnt, Sonic Hedgehog, TGFβ, and miRNA Signalings Are PotentialTargets for Oral Cancer Therapy. Int J Mol Sci. 2017 Jul 14;18(7). (IF:3.23, 52/148, CHEMISTRY, MULTIDISCIPLINARY).
    3. Hsu CW, Chen YC, Su HH, Huang GJ, Shu CW, Wu TT, Pan HW. Targeting TPX2 Suppresses the Tumorigenesis of Hepatocellular Carcinoma Cells Resulting in Arrested Mitotic Phase Progression and Increased Genomic Instability. J Cancer.2017 May 12;8(8):1378-1394. (IF:2.92, 113/217, ONCOLOGY).
    4. Liu PF, Kang BH, Wu YM, Sun JH, Yen LM, Fu TY, Lin YC, Liou HH, Lin YS, Sie HC, Hsieh IC, Tseng YK, Shu CW, Hsieh YD, Ger LP. Vimentin is a potential prognostic factor for tongue squamous cell carcinoma among five epithelial-mesenchymal transition-related proteins. PLoS One. 2017 Jun1;12(6):e0178581. (IF:2.806, 11/63, CHEMISTRY, MULTIDISCIPLINARY).
    5. Tsai WL*, Cheng JS, Shu CW, Lai KH, Chan HH, Wu CC, Wu JM, Hsu PI, Chung RT, Chang TH*. Asunaprevir evokes hepatocytes innate immunity to restrict the replication of hepatitis C and dengue virus.  Frontiers in Microbiology, 2017 Apr 20;8:668. (IF:4.165, SCI, 23/123, Microbiology).
    6. Wei-Chun Huang, Meng-Wei Ke, Chin-Chang Cheng, Shih-Hwa Chiou, Shue-Ren Wann, Shu CW, Kuan-Rau Chiou, Ching-Jiunn Tseng, Hung-Wei Pan, Guang-Yuan Mar, Chun-Peng Liu* Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-induced Pulmonary Arterial Hypertension Plos One 2016 (accepted, IF: 3.534, 8/55, CHEMISTRY, MULTIDISCIPLINARY).
    7. Fu TY, Wu CN, Sie HC, Cheng JT, Lin YS, Liou HH, Tseng YK, Shu CW, Tsai KW, Yen LM, Tseng HW, Tseng CJ, Ger LP, Liu PF. Subsite-specific association of DEAD box RNA helicase DDX60 with the development and prognosis of oral squamous cell carcinoma Oncotarget. 2016 Nov 8. doi: 10.18632/oncotarget.13197 (IF:5.415, SCI, 36/213, ONCOLOGY).
    8. Farooqi AA, Tang JY, Li RN, Ismail M, Chang YT, Shu CW, Yuan SS, Liu JR, Mansoor Q, Huang CJ, Chang HW. Epigenetic mechanisms in cancer: push and pull between kneaded erasers and fate writers. Int J Nanomedicine. 2015 Apr 24;10:3183-91. doi: 10.2147/IJN.S82527. eCollection 2015. Review. (IF: 4.383, 30/254, PHARMACOLOGY & PHARMACY)
    9. Yang Z, Wilkie-Grantham RP, Yanagi T, Shu CW, Matsuzawa SI, Reed JC. ATG4B (Autophagin-1) phosphorylation modulates autophagy. J Biol Chem. 2015 Oct30;290(44):26549-61. (IF: 4.693, 61/290, BIOCHEMISTRY & MOLECULAR BIOLOGY)
    10. Wang SL, Hwang TL, Chung MI, Sung PJ, Shu CW, Cheng MJ, Chen JJ. New Flavones, a 2-(2-Phenylethyl) -4H-chromen-4-one Derivative, and Anti-Inflammatory Constituents from the Stem Barks of Aquilaria sinensis. Molecules. 2015 Nov 24;20(11):20912-25. doi: 10.3390 /molecules201119736. (IF: 2.416, 22/58, CHEMISTRY, ORGANIC)
    11. Cho FN, Chang TH, Shu CW, Ko MC, Liao SK, Wu KH, Yu MS, Lin SJ, Hong YC, Chen CH, Hung CH, Chang YH. Enhanced cytotoxicity of natural killer cells following the acquisition of chimeric antigen receptors through trogocytosis. PLoS One. 2014 Oct 14;9(10):e109352. doi: 10.1371/journal.pone.0109352. eCollection 2014. (IF: 3.534, 8/55, CHEMISTRY, MULTIDISCIPLINARY).
    12. Chen LC, Lee TH, Sung PJ, Shu CW, Lim YP, Cheng MJ, Kuo WL, Chen JJ. New Thymol Derivatives and Cytotoxic Constituents from the Root of Eupatorium cannabinum ssp. asiaticum. Chem Biodivers. 2014 Sep;11(9):1374-80. (IF:1.795, 63/148, CHEMISTRY, MULTIDISCIPLINARY)
    13. Lee TH, Chen YC, Hwang TL, Shu CW, Sung PJ, Lim YP, Kuo WL, Chen JJ. New coumarins and anti-inflammatory constituents from the fruits of Cnidium monnieri. Int J Mol Sci. 2014 May 8;15(6):9566-78. doi: 10.3390/ijms15069566. (IF:2.339, 52/148, CHEMISTRY, MULTIDISCIPLINARY)
    14. Chen WS, Chen TW, Yang TH, Hu LY, Pan HW, Leung CM, Li SC, Ho MR, Shu CW, Liu PF, Yu SY, Tu YT, Lin WC, Wu TT, Tsai KW. Co-modulated behavior and effects of differentially expressed miRNA in colorectal cancer. BMC Genomics. 2013;14 Suppl 5:S12. doi: 10.1186/1471-2164-14-S5-S12. (IF: 4.397, 21/160, BIOTECHNOLOGY & APPLIED MICROBIOLOGY).
    15. Shu CW*, Liu PF, Huang CM. High throughput screening for drug discovery of autophagy modulators. Comb Chem High Throughput Screen. 2012 Nov;15(9):721-9. Review.  (IF: 1.925, 23/71, CHEMISTRY, APPLIED ).
    16. Kuang E, Okumura CY, Sheffy-Levin S, Varsano T, Shu CW, Qi J, Niesman IR, Yang HJ, Lopez-Otin C, Yang WY, Reed JC, Broday L, Nizet V, Ronai ZA (2012, Oct). Regulation of ATG4B Stability by RNF5 Limits Basal Levels of Autophagy and Influences Susceptibility to Bacterial Infection. PLoS Genet, 8: e1003007. (IF: 8.167, 14/165, GENETICS & HEREDITY ).
    17. Sano R, Hou YC, Hedvat M, Correa RG, Shu CW, Krajewska M, Diaz PW, Tamble CM, Quarato G, Gottlieb RA, Yamaguchi M, Nizet V, Dahl R, Thomas DD, Tait SW, Green DR, Fisher PB, Matsuzawa S, Reed JC. Endoplasmic reticulum protein BI-1 regulates Ca²⁺-mediated bioenergetics to promote autophagy. Genes Dev. 2012 May 15;26(10):1041-54. doi: 10.1101. (IF: 12.639, 7/165, GENETICS & HEREDITY). 
    18. Innocenzi A, Latella L, Messina G, Simonatto M, Marullo F, Berghella L, Poizat C, Shu CW, Wang JY, Puri PL, Cossu G. An evolutionarily acquired genotoxic response discriminates MyoD from Myf5, and differentially regulates hypaxial and epaxial myogenesis. EMBO Rep. 2011 Feb;12(2):164-71. doi: 10.1038/embor.2010.195. (IF: 7.189, 32/290 BIOCHEMISTRY & MOLECULAR BIOLOGY). 
    19. Chang KC, Lo CW, Fan TC, Chang MD, Shu CW, Chang CH, Chung CT, Fang SL, Chao CC, Tsai JJ, Lai YK. TNF-alpha mediates eosinophil cationic protein-induced apoptosis in BEAS-2B cells. BMC Cell Biol. 2010 Jan 20;11:6. doi: 10.1186/1471-2121-11-6. (IF: 2.808, 106/185, CELL BIOLOGY). 
    20. Hayashi, H., Cuddy, M., Shu CW., Yip, K.W., Madiraju, C., Diaz, P.,Vasile, S., Sergienko, E., and Reed, J.C. (2009, Oct). Versatile assays for high throughput screening for activators or inhibitors of intracellular protease and their cellular regulators. PLoS ONE, 4(10):e7655. (IF: 3.730, 7/56, MULTIDISCIPLINARY SCIENCES).
    21. Shu CW*, Huang CM. HSP70s: From Tumor Transformation to Cancer Therapy. Clin Med Oncol. 2008;2:335-45. Epub 2008 Apr 24. (IF: 1.317, 70/155, MEDICINE, GENERAL & INTERNAL).
    22. Lin CC, Hsu JT, Huang KL, Tang HK, Shu CW, Lai YK. Sf-Caspase-1-repressed stable cells: resistance to apoptosis and augmentation of recombinant protein production. Biotechnol Appl Biochem. 2007 Sep;48(Pt 1):11-9. (IF: 1.348, 112/160,BIOTECHNOLOGY & APPLIED MICROBIOLOGY)

    Oral presentation:

    1. Shu C. W.  High-Throughput Screening for Small Molecule Inhibitors of Autophagins/Atg4. 2011. Autophagy keystone symposia, Whistler, Canada.
    2. Shu C. W.  High-Throughput Screening for Autophagins/Atg4 antagonist for cancer therapy. 2010. Cell Death/Survival meeting, San Diego, CA, U.S.A.

    Poster presentation:

    1. Liu PF, Cheng JS, Sy CL, Huang WC, Yang HC, Gallo RL, Huang CM, Shu CW*. IsaB promotes host transmission of methicillin-resistant Staphylococcus aureus by inhibiting autophagy. 2015 Autophagy keystone symposium. HuangShan.  China.

    2. Liu PF, Leung CM, Chang YS, Cheng JS, Chen JJ, Weng CJ, Tsai KW, Hsu CJ, Liu YC, Hsu PC, Pan HW, Shu CW* ATG4B promotes colorectal cancer growth independent of autophagic flux. 2014 Autophagy keystone symposium. TX, USA.

    3. Liu P.F., Reed, J.C., Shu C. W.  High throughput screening kinase activators of Atg4B for cancer therapy. 2013. American Association Cancer Research.  U.S.A.

    4. Shu C.W., Godoi P., Welsh K., Madiraju C., Zhai D., Diaz P., Drag M., Salvesen G., Sano R., and Reed J. C. High-Throughput Screening for Small Molecule Inhibitors of Autophagins/Atg4 for Cancer Therapy. 2010.  Sass foundation annual meeting. NY, U.S.A.

    5. Shu C.W., Drag M., Salvesen G., Godoi P., Diaz P., and Reed J.C.  Chemical inhibitors of Autophagins for cancer therapy.  2009.  Sass foundation annual meeting. NY, U.S.A.

    6. Shu C.W., Lin C.C., Chang J.L., Hsu H.C., Chang K.C., and Lai Y.K. Raf-1 is required for GRP78 to suppress endoplasmic reticulum stress-induced apoptosis. 2007. 4th poster competition of National Tsing Hua University, Hsinchu, Taiwan. 

    7. Shu C.W., Sun F.C., Lai Y.K. Cooperation of GRP78 and Raf-1 to Inhibit Apoptosis in Human Non-Small Cell Lung Cancer H460 Cells Under Endoplasmic Reticulum Stress. 2006. 46th Annual Meeting of the American Society of Cell Biology. San Diego, CA, U.S.A.

    8. Shu C.-W., N.-L. Cheng, W.-M. Chang, and Y.-K. Lai. Transactivation of hsp70-1/2 in geldanamycin-treated human non-small cell lung cancer H460 cells: involvement of intracellular calcium and protein kinase C. 2004. 10th Society of Chinese Bioscientists in America, Beijing, China

    Professional memberships:

    1. 台灣生物化學及分子生物學會(2016-present)
    2. 中華民國細胞及分子生物學會(2012-present)
    3. American Association Cancer Research, USA. (2012-present)
    4. Autophagy keystone symposia, USA. (2010-present)
    5. Protein Society. USA. (2007-2008)  
    6. American Society for Cell Biology. USA. (2006-2008)  
    7. Society of Chinese Bioscientists in America. USA. (2004-2006)

    實驗室成員 吳芷瑄,楊琇真,曾和馨,李政昕

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