莊宗顯 研究員

Dr. Tsung-Hsien Chuang                                                                            Profile updated: Oct. 17, 2018

Investigator                                                                                                     ResearcherID: F-9679-2010

Immunology Research Center, National Health Research Institutes


[Contact Information]

Phone    +886-37-206166 Ext. 37611 / 37617

Fax          +886-37-586642

Email       thchuang@nhri.edu.tw

Address  35 Keyan Road, Zhunan, Miaoli County 350, Taiwan (R.O.C.)


Educations and Positions

  • 1992             Ph.D. Iowa State University,
  • 1992-2008   Postdoctoral Research Associate through Associate Professor of Immunology, The Scripps Research Institute, USA
  • 2008-2010   Associate Professor, Sidney Kimmel Cancer Center, USA  / Associate Investigator, Sanford-Burnham Medical Research Institute, USA
  • 2010-2017     Associate Investigator, Immunology Research Center, National Health Research Institutes, Taiwan
  • 2017-present   Investigator, Immunology Research Center, National Health Research Institutes, Taiwan

Honors and Services

  • 1993-1996   Arthritis Postdoctoral Fellowship, Arthritis Foundation
  • 1996-1997   Postdoctoral Fellowship, American Heart Association, Western states Affiliate
  • 1997-2000   Arthritis Investigator Award, Arthritis Foundation
  • 1997-2000   Hulda Irene Duggan Arthritis Investigator, Arthritis Foundation
  • 1999-2001   Beginning Grant-in-Aid, American Heart Association, Western States Affiliate
  • 2008  Panel member, DOD Prostate Cancer Research Program, Immunological Science Study  Section.
  • 2009  Panel member, DOD Breast Cancer Research Program, Immunological Science Study Section.
  • 2010  Online Reviewer, DOD Prostate Cancer Research Program, PRE-IMM Study Section.
  • 2010  Panel member, DOD Breast Cancer Research Program, Immunological Science Study Section.

Publications

  1. Chuang TH, Xu X, Knaus UG, Hart MJ, and Bokoch GM. (1993) GDP dissociation inhibitor prevents intrinsic and GTPase activating protein-stimulated GTP hydrolysis by the Rac GTP-binding protein. J. Biol. Chem. 268: 775-778.
  2. Chuang TH,Bohl BJ, and Bokoch GM. (1993) Biologically active lipids are regulators of Rac.GDI complexation. J. Biol. Chem. 268: 26206-26211.
  3. Chuang TH,Xu X, Quilliam LA and Bokoch GM. (1994) SmgGDS stabilizes nucleotide-bound and -free forms of the Rac1 GTP-binding protein and stimulates GTP/GDP exchange through a substituted enzyme mechanism. Biochem. J. 303(3): 761-767.
  4. Bokoch GM, Bohl BP, and Chuang TH.(1994) Guanine nucleotide exchange regulates membrane translocation of Rac/Rho GTP-binding proteins. J. Biol. Chem. 269: 31674-31679.
  5. Chuang TH,Xu X, Kaartinen V, Heisterkamp N, Groffen J, and Bokoch GM. (1995) Abr and Bcr are multifunctional regulators of the Rho GTP binding protein family. Proc. Natl. Acad. Sci. USA. 92: 10282-10286.
  6. Chuang TH,Hamilton RT, and Nilsen-Hamilton M. (1995) Cloning of mink plasminogen activator inhibitor type 1 messenger RNA: a mRNA with a short life. Gene 162: 303-308.
  7. Danley DE, Chuang TH,and Bokoch GM. (1996) Defective Rho GTPase regulation by IL-1ß converting enzyme mediated cleavage of D4 GDP dissociation  inhibitor. J. of Immunol. 157:500-503.
  8. Martin SJ, Amarante-Mendes GP, Tewari M, Shi L, Chuang TH,Casciano  C, Fitzgerald P, Tan EM, Bokoch GM, Dixit VM, Greenberg AH, and Green DR. (1996) The cytotoxic cell protease granzyme B initiates apoptosis by  proteolytic processing and activation of the ICE/CED-3-family protesae, cpp32. EMBO J. 15: 775-779.
  9. Na S, Chuang TH,Cunningham A, Turi TG, Hanke JH, Bokoch GM, and Danley DE.  (1996) D4 GDI, a substrate of CPP32, is proteolyzed during Fas-induced  apoptosis. J. Biol. Chem. 271: 11209-11213.
  10. Lamaze C, Chuang TH,Terlecky LJ, Bokoch GM, and Schmid SL. (1996) Regulation of receptor-mediated endocytosis by Rho and Rac. Nature 382: 177-179.
  11. Chuang TH.Hahn KM. Lee JD, Danley DE, and Bokoch GM. (1997). The small GTPase Cdc42 initiates an apoptotic signaling pathway in Jurkat T lymphocytes.  Mol. Biol. Cell. 8, 1687-1698.
  12. Thomas R, Frank Z, Chuang TH,and Bokoch, GM. (1998) p21-activated kinase 2 (PAK2) induces apoptosis and is required for Fas-induced JNK activation  in Jurkat T cells. J. of Immunol. 160: 7-11.
  13. Subauste MC, Herrath MV, Benard V, Chamberlain C., Chuang TH,Chu K, Bokock GM, and Hahn KM. (2000) Rho family proteins modulate rapid apoptosis induced by cytotoxic T lymphocytes and Fas. J. Biol. Chem. 275: 9725-9733.
  14. Chuang TH,and Ulevitch RJ. (2000) Cloning and characterization of a sub-family of human Toll-like receptors: hTLR7, hTLR8 and hTLR9. Eur. Cytokine Network. 11: 372-378.
  15. Chuang TH, and Ulevitch RJ. (2000) Identification of hTLR10: A novel human Toll-like receptor preferentially expressed in immune cells. Biochem. Biophys. Acta. 1518: 157-161.
  16. Werts C, Tapping RI, Mathison JC, Chuang TH,Kravchenko V, Girons IS, Haake DA, Godowski PJ, Hayashi F, Ozinsky A, Underhill DM, Kirschning CJ, Wagner H, Aderem A, Tobias PS, and Ulevitch  RJ. (2001) Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism. Nat. Immunol. 2: 346-352.
  17. Golovanov AP*Chuang TH*,DerMardirossian C, Barsukov I, Haekins R, Badii R, Bokoch GM, Lian LY, and Roberts, G.C. (2001) Structure-activity relationships in flexible protein domains: regulation Rho GTPase by Rho GDI and D4 GDI. J. Mol. Biol. 305:  121-135.  (* equal contribution)
  18. Chuang TH*,Lee J, Kline L, Mathison JC, and Ulevitch RJ (2002) Toll-like receptor 9 mediates CpG-DNA signaling  and distinguishes different CpG motifs and  backbones. J. Leuko. Biol. 71, 538-554. (* corresponding author)
  19. Lee J, Chuang TH,Redecke V, She L, Pitha PM, Carson DA, Raz E, and Cottom HB. (2003) Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of Toll-like Receptor 7. Proc. Natl. Acad. Sci. USA. 100(11): 6646-51.
  20. Chuang TH,and Ulevitch RJ. (2004) Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors. Nat. Immunol. 5(5):495-502.
  21. Zhang P, Chan J, Dragoi AM, Gong X, Ivanov S, Li ZW, Chuang TH, Tuhill C, Wan Y, Karin M, and Chu WM. (2005) Activation of IKK by thymosin alpha1 requires the TRAF6 signalling pathway. EMBO Rep. 6(6): 531-7.
  22. Wang T*, Chuang TH*, Ronni T*, Gu S, Du YC, Cai H, Sun HQ, Yin HL, and Chen X.(2006) Flightless I homolog negatively modulates the TLR pathway. J. Immunol.176(3):1355-62. (equal contribution)
  23. Lee J, Wu CC, Lee KJ, Chuang TH, Katakura K, Liu YT, Chan M, Tawatao R, Chung M, Shen C, Cottom HB, Lai MM, Raz E, and Carson DA. (2006) Activation of anti-hepatitis C virus responses via Toll-like receptor 7. Proc. Natl. Acad. Sci. USA. 103(6):1828-33.
  24. Fearns C, Pan Q, MathisonJC, and Chuang TH. (2006) Triad3A regulates ubiquitination and proteasomal degradation of RIP1 following disruption of Hsp90 binding. J Biol Chem. 281(45): 34592-600.
  25. Lee J, Hayashi M, Lo JF, Fearns C, Chu WM, Xiang R, and Chuang TH.(2009) NF-kB activation primes cells to a pro-inflammatory polarized response to a TLR7 agonist. Biochem. J. 421(2):301-10.
  26. Nakhaei P,  Mesplede T, Solis M, Sun Q, Zhao T,  Yang L, Chuang TH,  Ware CF, Lin R, and Hiscott J. (2009) The E3 ubiquitin ligase Triad3Anegatively regulates the RIG-I/MAVS signaling pathway by targeting TRAF3 for degradartion. PLoS Pathog. 5(11):e1000650.
  27. Luo Y, ZhouH, Krueger J, Kaplan C, Liao D, Markowitz D, Liu C, Chen T, Chuang TH, Xiang R, and Reisfeld RA (2010) The role of proto-oncogene Fra-1 in remodeling the tumor microenvironment in support of breast tumor cell invasion and progression. Oncogene. 4;29(5):662-73.
  28. Liu J, Xu C, Hsu LC,  Luo Y, Xiang R, and Chuang TH. (2010) A five amino acids motif at  the undefined region of TLR8 ectodomain is required for species-specific recognition of agonists. Mol Immunol. 47(5):1083-1090.
  29. Xiang R, Liao D, Cheng T, Zhou H, Shi Q, Chuang TH, Markowitz D, Reisfeld RA, Luo Y. (2011) Downregulation of transcription factor SOX2 in cancer stem cells suppresses growth and metastasis  of lung cancer. Br J Cancer. 104(9):1410-7.
  30. Xu C, Liu J, Hsu LC, Luo Y, Xiang R, and Chuang TH.(2011) Functional interaction of Hsp90 and Beclin1 Modulates Toll-like receptors mediated autophagy. FASEB J. 25(8):2700-10.
  31. Chen YS, Wu MJ, Huang CY, Lin SC, Chuang TH,Yu CC, and Lo JF. (2011) CD133/Src Axis Mediates Tumor Initiating Property and Epithelial-Mesenchymal Transition of Head and Neck Cancer. PLoS One. 2011;6(11):e28053.
  32. Liu J, Xu C, Liu YL , Matsuo H, Hsieh RP, Lo JF, Tseng PH, Yuan CJ, Luo Y, Xiang R, and Chuang TH. (2012) Activation of rabbit TLR9 by different CpG-ODN optimized for mouse and human TLR9.Comp Immunol Microbiol Infect Dis. 35(5):443-51.
  33. 33.Daniel J. Klionsky and 1269 other authors including Chuang TH. (2012) Guidelines for the use and interpretation of assays for monitoring autophagy (2nd  Ed). Autophagy. 8(4):445-544.. (Review)
  34. Yang J, Liao D, Chen C, Liu Y, Chuang TH, Xiang R, Markowitz D, Reisfeld RA, and Luo Y.(2012) Tumor associated macrophages regulate murine breast cancer stem cells through a novel paracrine EGFR/Stat3/Sox-2 signaling pathway. Stem Cells. 31(2):248-58.
  35. Ho CC, Luo YH, Chuang TH, Yang CS, Ling YC, and Lin P. (2013) Quantum dots induced monocyte chemotactic protein-1 expression via MyD88-dependent Toll-like receptor signaling pathways in macrophages. Toxicology. 308C:1-9.
  36. Chuang SY, Yang CH, Chou CC, Chiang YP, Chuang TH, Hsu LC. (2013) TLR-induced PAI-2 expression suppresses IL-1β processing via increasing autophagy and NLRP3 degradation. Proc Natl  Acad Sci U S A. 110(40):16079-84.
  37. Yeh DH, Liu YL, LoYC, Yuh CH, Yu GY, Lo JF, Luo Y, Xiang R, and Chuang TH (2013) Toll-like receptor 9 and 21 have different ligand recognition profiles and cooperatively mediate activity of CpG-oligodeoxynucleotides in zebrafish. Proc Natl  Acad Sci U S A. 110(51):20711-6.
  38. 38.Yang J, Zhang Z, Chen C, Liu Y, Si Q, Chuang TH, Li N, Gomez-Cabrero A, Reisfeld RA, Xiang R, Luo Y. (2014) MicroRNA-19a-3p inhibits breast cancer progression and metastasis by inducing macrophage polarization through downregulated expression of Fra-1 proto-oncogene. Oncogene. 33(23):3014-23.
  39. Hsieh MY, Chang MY, Chen YJ, Li YK, Chuang TH, Yu GY, Cheung CH, Chen HC, Maa MC, Leu TH.(2014) The iNOS/Src Axis Mediates Toll-Like Receptor 3 Tyrosine 759 phosphorylation and Enhances Its Signal Transduction Leading to Interferon-β Synthesis in Macrophages. J Biol Chem.289(13):9208-20.
  40. Chuang TH, Lai CY, Tseng PH, Yuan CJ, Hsu LC. (2014) Development of CpG-oligodeoxynucleotides for effective activation of rabbit TLR9 mediated immune responses.PLoS One. 9(9):e108808.
  41. Lai CY, Liu YL, Yu GY, Maa MC, Leu TH, Xu C, Luo Y, Xiang R, Chuang TH. (2014) TLR7/8 agonists activate a mild immune response in rabbits through TLR8 but not TLR7. Vaccine. 32(43):5593-9.
  42. Xu C, Feng K, Zhao X, Huang S, Cheng Y, Qian L, Wang Y, Sun H, Jin M, Chuang TH, Zhang Y. (2014) Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination. Autophagy. 10(12):2239-50.
  43. Kuo YL, Chen CH, Chuang TH, Hua WK, Lin WJ, Hsu WH, Chang PM, Hsu SL, Huang TH, Kao CY, Huang CY. (2015) Gene Expression Profiling and Pathway Network Analysis Predicts a Novel Antitumor Function for a Botanical-Derived Drug, PG2. Evid Based Complement Alternat Med. 2015:917345.
  44. Chen C, Cao F, Bai L, Liu Y, Xie J, Wang W, Si Q, Yang J, Chang A, Liu D, Liu D, Chuang TH, Xiang R, Luo Y.(2015) IKKβ Enforces a LIN28B/TCF7L2 Positive Feedback Loop That Promotes Cancer Cell Stemness and Metastasis. Cancer Res. 75(8):1725-35.
  45. Chang A, Chen Y, Shen W, Gao R, Zhou W, Yang S, Liu Y, Luo Y, Chuang TH, Sun P, Liu C, Xiang R. (2015) Ifit1 Protects Against Lipopolysaccharide and D-galactosamine-Induced Fatal Hepatitis by Inhibiting Activation of the JNK Pathway. J Infect Dis.;212(9):1509-20.
  46. Lai CY, Yeh DW, Lu CH, Liu YL, Huang LR, Kao CY, Chen HY, Huang CY, Chang CH, Luo Y, Xiang R, Chuang TH. (2015) Identification of Thiostrepton as a Novel Inhibitor for Psoriasis-like Inflammation Induced by TLR7-9. J Immunol. 195(8):3912-21.
  47. Yeh DW, Chen YS, Lai CY, Liu YL, Lu CH, Lo JF, Chen L, Hsu LC, Luo Y, Xiang R, Chuang TH. (2016) Downregulation of COMMD1 by miR-205 promotes a positive feedback loop for amplifying inflammatory- and stemness-associated properties of cancer cells..Cell Death Differ. 23(5):841-52.
  48. Daniel J. Klionsky et. al. including Chuang TH.(2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3 rd  edition). Autophagy. 12(1):1-222.
  49. Tsai MH, Chang CH, Tsai RK, Hong YR, Chuang TH, Fan KT, Peng CW, Hsu WL, Wang LS, Chen LK,Wu CY, Yu HS (2016) Crossregulation of Proinflammatory Cytokines by Interleukin10 and MiR155 in Orientia tsutsugamushiinfected Human Macrophages Prevents Cytokine Storm.J Invest Dermatol. 136(7):1398-407.
  50. Ho CC, Luo YH, Chuang TH, Lin P. (2016) Quantum dots induced interferon beta expression via TRIF-dependent signaling pathways by promoting endocytosis of TLR4. Toxicology.17;344-346:61-70.Lin KH, Chang LS, Tian CY, Yeh YC, Chen YJ, Chuang TH, Liu SJ, Leng CH.(2016) Carboxyl-terminal fusion of E7 into Flagellin shifts TLR5 activation to NLRC4/NAIP5 activation and induces TLR5-independent anti-tumor immunity.Sci Rep. 6:24199.
  51. Tsai WT, Lo YC, Wu MS, Li CY, Kuo YP, Lai YH, Tsai Y, Chen KC, Chuang TH, Yao CH, Lee JC, Hsu LC, Hsu JT, Yu GY. (2016) Mycotoxin patulin suppresses innate immune responses by mitochondrial dysfunction and p62/sequestosome-1-dependent mitophagy. J Biol Chem. 291(37):19299-311.
  52. Yeh DW, Huang LR, Chen YW,  Huang CY andChuang TH(2016) Interplay between inflammation and stemness in cancer cells: The role of Toll-like receptor signaling. J of Imm Res. Article ID 4368101.
  53. Yang JX, Hsieh KC, Chen YL, Lee CK, Conti M, Chuang TH, Wu CP, Jin SC. (2017)Phosphodiesterase 4B negatively regulates endotoxin-activated interleukin-1 receptor antagonist responses in macrophages.Sci Rep. 6;7:46165. doi: 10.1038/srep46165.
  54. Jian SL, Chen WW, Su YC, Su YW, Chuang TH, Hsu SC, Huang LR. (2017) Glycolysis regulates the expansion of myeloid-derived suppressor cells in tumor-bearing hosts throughprevention of ROS-mediated apoptosis. Cell Death Dis. 2017 May 11;8(5):e2779.
  55. Lai CY, Su YW, Lin KI, Hsu LC, Chuang TH. (2017) Natural Modulators of Endosomal Toll-Like Receptor-Mediated Psoriatic Skin Inflammation. J Immunol Res. 2017:7807313.
  56. Yeh DW, Lai CY, Liu YL, Lu CH, Tseng PH, Yuh CH, Yu GY, Liu SJ, Leng CH, Chuang TH. (2017) CpG-oligodeoxynucleotides developed for grouper toll-like receptor (TLR) 21s effectively activate mouse and human TLR9s mediated immune responses. Sci Rep. 2017 Dec 11;7(1):17297. (IF=4.259; Journal ranking :10/64, Multidisciplinary sciences)
  57. Kuo YP, Tsai KN, Luo YC, Chung PJ, Su YW, Teng Y, Wu MS, Lin YF, Lai CY, Chuang TH, Dai SS, Tseng FC, Hsieh CH, Tsai DJ, Tsai WT, Chen CH, Yu GY. (2018) Establishment of a mouse model for the complete mosquito-mediated transmission cycle of Zika virus. PLoS Negl Trop Dis. 12(4):e0006417. (IF=3.834; Journal ranking :1/19, Tropical Medicine)
  58. Lu CH, Yeh DW, Lai CY, Liu YL, Huang LR, Lee AY, Jin SC, Chuang TH.(2018) USP17 mediates macrophage-promoted inflammation and stemness in lung cancer cells by regulating TRAF2/TRAF3 complex formation. Oncogene. 2018 Jul 23. doi: 10.1038/s41388-018-0411-0.
  59. Ko YA, Chan YH, Liu CH, Liang JJ, Chuang TH, Hsueh YP, Lin YL, Lin KI. (2018) Blimp-1-Mediated Pathway Promotes Type I IFN Production in Plasmacytoid Dendritic Cells by Targeting to Interleukin-1 Receptor-Associated Kinase M. Front Immunol.;9:1828. doi: 10.3389/fimmu.2018.01828. eCollection 2018.
  60. Chen MY, Hsu WC, Hsu SC, Yang YS, Chuang TH, Lin WJ, Tan TH, Su YW (2018) PP4 deficiency leads to DNA replication stress that impairs immunoglobulin class switch efficiency. Cell Death and Differ. doi: 10.1038/s41418-018-0199-z. [Epub ahead of print].

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