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曾炳輝

曾炳輝

  • 職稱: 副教授
  • 學歷: PhD, Pharmacy, Ohio State University, USA; Post-doc, Pharmacology, University of California San Diego, USA
  • 辦公室: 傳醫乙棟 七樓 R706室
  • 電話: 886-2-2826-7234
  • Email這個 E-mail 地址已經被防止灌水惡意程式保護,您需要啟用 Java Script 才能觀看
  • 個人網頁
研究領域--訊息傳遞及後轉譯修飾; Toll-like receptors和 TNF receptors的分子機制研究
  • The focus of our lab is to understand the molecular mechanisms of Toll-like receptors (TLRs) and TNF receptors (TNFR) pathways, which are involved in innate immunity and cancer immunology. We are interested in how posttranslational modifications, in particular ubiquitination, regulate differential activation of downstream signaling, such as NF-kappaB, MAPK, IRF and PI3K, and lead to distinct biological outcomes. Our current studies addressed the roles of ubiquitin E3 ligases and the modes of polyubiquitination in TNFRs and TLRs. We found that c-IAP1/2-mediated TRAF3 degradation is critical for cytosolic translocation of the receptor-assembled complex, which is essential for MAPK activation in CD40, a TNFR family member. Also, we demonstrated that differential ubiquitination (K48-linked or K63-linked) of TRAF3 controls the balance of proinflammatory cytokines and type I interferons in TLR4 signaling. Based on these finding, particular issues will be explored, including (1) the regulation of ubiquitination cascades involving TRAFs, IRAK, MAP3K, c-IAP and IKKgamma, and the their roles in complex recruitment and signal activation; (2) to identify ubiquitination sites and ubiquitination interaction motifs; (3) the balance between ubiquitination and deubiquitination, and differential regulation through K48- and K63-linked ubiquitination for cytokines production in TNFRs- or TLRs-related diseases, such as autoimmune disease and cancer progression; (4) The cross-talk of TLRs or TNFRs with other signal pathways, such as TGFbeta and PI3K/Akt.

研究著作
  • Su, J. C., Chang, J. H., Huang, J. W., Chen, P. P., Chen, K. F., Tseng, P. H.*, and Shiau, C. W.* (2015) Copper-obatoclax derivative complexes mediate DNA cleavage and exhibit anti-cancer effects in hepatocellular carcinoma. Chem Biol Interact 228, 108-113 (Co-corresponding Authors)

 

  • Chen, I. T., Hsu, P. H., Hsu, W. C., Chen, N. J., and Tseng, P. H.* (2015) Polyubiquitination of Transforming Growth Factor beta-activated Kinase 1 (TAK1) at Lysine 562 Residue Regulates TLR4-mediated JNK and p38 MAPK Activation. Sci Rep 5, 12300

 

  • Su, J. C., Tseng, P. H., Wu, S. H., Hsu, C. Y., Tai, W. T., Li, Y. S., Chen, I. T., Liu, C. Y., Chen, K. F., and Shiau, C. W. (2014) SC-2001 overcomes STAT3-mediated sorafenib resistance through RFX-1/SHP-1 activation in hepatocellular carcinoma. Neoplasia 16, 595-605

 

  • Su, J. C., Tseng, P. H., Hsu, C. Y., Tai, W. T., Huang, J. W., Ko, C. H., Lin, M. W., Liu, C. Y., Chen, K. F., and Shiau, C. W. (2014) RFX1-dependent activation of SHP-1 induces autophagy by a novel obatoclax derivative in hepatocellular carcinoma cells. Oncotarget 5, 4909-4919

 

  • Su, J. C., Chiang, H. C., Tseng, P. H., Tai, W. T., Hsu, C. Y., Li, Y. S., Huang, J. W., Ko, C. H., Lin, M. W., Chu, P. Y., Liu, C. Y., Chen, K. F., and Shiau, C. W. (2014) RFX-1-dependent activation of SHP-1 inhibits STAT3 signaling in hepatocellular carcinoma cells. Carcinogenesis 35, 2807-2814

 

  • Chuang, T. H., Lai, C. Y., Tseng, P. H., Yuan, C. J., and Hsu, L. C. (2014) Development of CpG-oligodeoxynucleotides for effective activation of rabbit TLR9 mediated immune responses. PLoS One 9, e108808

 

  • Chang, Y. L., Chen, T. H., Wu, Y. H., Chen, G. A., Weng, T. H., Tseng, P. H., Hsieh, S. L., Fu, S. L., Lin, C. H., Chen, C. J., Chu, C. L., Chio, II, Mak, T. W., and Chen, N. J. (2014) A novel TLR2-triggered signalling crosstalk synergistically intensifies TNF-mediated IL-6 induction. J Cell Mol Med 18, 1344-1357

 

  • Liu, J., Xu, C., Liu, Y. L., Matsuo, H., Hsieh, R. P., Lo, J. F., Tseng, P. H., Yuan, C. J., Luo, Y., Xiang, R., and Chuang, T. H. (2012) Activation of rabbit TLR9 by different CpG-ODN optimized for mouse and human TLR9. Comparative immunology, microbiology and infectious diseases 35, 443-451
  • Hacker, H., Tseng, P. H., and Karin, M. (2011) Expanding TRAF function: TRAF3 as a tri-faced immune regulator. Nat Rev Immunol 11, 457-468

 

  • Zhang, W., Kater, A. P., Widhopf, G. F., 2nd, Chuang, H. Y., Enzler, T., James, D. F., Poustovoitov, M., Tseng, P. H., Janz, S., Hoh, C., Herschman, H., Karin, M., and Kipps, T. J. (2010) B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 107, 18956-18960

 

  • Tseng, P. H.#, Matsuzawa, A.#, Zhang, W., Mino, T., Vignali, D. A., and Karin, M. (2010) Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines. Nat Immunol 11, 70-75 (# equal contribution)

 

  • Wang, H., Matsuzawa, A., Brown, S. A., Zhou, J., Guy, C. S., Tseng, P. H., Forbes, K., Nicholson, T. P., Sheppard, P. W., Hacker, H., Karin, M., and Vignali, D. A. (2008) Analysis of nondegradative protein ubiquitylation with a monoclonal antibody specific for lysine-63-linked polyubiquitin. Proc Natl Acad Sci U S A 105, 20197-20202

 

  • Vallabhapurapu, S., Matsuzawa, A., Zhang, W., Tseng, P. H., Keats, J. J., Wang, H., Vignali, D. A., Bergsagel, P. L., and Karin, M. (2008) Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling. Nat Immunol 9, 1364-1370

 

  • Matsuzawa, A.#, Tseng, P. H.#, Vallabhapurapu, S., Luo, J. L., Zhang, W., Wang, H., Vignali, D. A., Gallagher, E., and Karin, M. (2008) Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. Science 321, 663-668 (# equal contribution)

 

  • Hsu, L. C., Ali, S. R., McGillivray, S., Tseng, P. H., Mariathasan, S., Humke, E. W., Eckmann, L., Powell, J. J., Nizet, V., Dixit, V. M., and Karin, M. (2008) A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci U S A 105, 7803-7808

 

  • Tseng, P. H., Wang, Y. C., Weng, S. C., Weng, J. R., Chen, C. S., Brueggemeier, R. W., Shapiro, C. L., Chen, C. Y., Dunn, S. E., Pollak, M., and Chen, C. S. (2006) Overcoming trastuzumab resistance in HER2-overexpressing breast cancer cells by using a novel celecoxib-derived phosphoinositide-dependent kinase-1 inhibitor. Mol Pharmacol 70, 1534-1541

 

  • Fang, Y. C., Wu, J. S., Chen, J. J., Cheung, W. M., Tseng, P. H., Tam, K. B., Shyue, S. K., Chen, J. J., and Lin, T. N. (2006) Induction of prostacyclin/PGI2 synthase expression after cerebral ischemia-reperfusion. J Cereb Blood Flow Metab 26, 491-501

 

  • Tseng, P. H., Lin, H. P., Zhu, J., Chen, K. F., Hade, E. M., Young, D. C., Byrd, J. C., Grever, M., Johnson, K., Druker, B. J., and Chen, C. S. (2005) Synergistic interactions between imatinib mesylate and the novel phosphoinositide-dependent kinase-1 inhibitor OSU-03012 in overcoming imatinib mesylate resistance. Blood 105, 4021-4027

 

  • Chen, C. S., Weng, S. C., Tseng, P. H., Lin, H. P., and Chen, C. S. (2005) Histone acetylation-independent effect of histone deacetylase inhibitors on Akt through the reshuffling of protein phosphatase 1 complexes. J Biol Chem 280, 38879-38887

 

  • Zhu, J., Huang, J. W., Tseng, P. H., Yang, Y. T., Fowble, J., Shiau, C. W., Shaw, Y. J., Kulp, S. K., and Chen, C. S. (2004) From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. Cancer Res 64, 4309-4318

 

  • Tseng, P. H., Lin, H. P., Hu, H., Wang, C., Zhu, M. X., and Chen, C. S. (2004) The canonical transient receptor potential 6 channel as a putative phosphatidylinositol 3,4,5-trisphosphate-sensitive calcium entry system. Biochemistry 43, 11701-11708

 

  • Lin, H. P., Kulp, S. K., Tseng, P. H., Yang, Y. T., Yang, C. C., Chen, C. S., and Chen, C. S. (2004) Growth inhibitory effects of celecoxib in human umbilical vein endothelial cells are mediated through G1 arrest via multiple signaling mechanisms. Mol Cancer Ther 3, 1671-1680

 

  • Kulp, S. K., Yang, Y. T., Hung, C. C., Chen, K. F., Lai, J. P., Tseng, P. H., Fowble, J. W., Ward, P. J., and Chen, C. S. (2004) 3-phosphoinositide-dependent protein kinase-1/Akt signaling represents a major cyclooxygenase-2-independent target for celecoxib in prostate cancer cells. Cancer Res 64, 1444-1451

 

  • Yang, C. C., Lin, H. P., Chen, C. S., Yang, Y. T., Tseng, P. H., Rangnekar, V. M., and Chen, C. S. (2003) Bcl-xL mediates a survival mechanism independent of the phosphoinositide 3-kinase/Akt pathway in prostate cancer cells. J Biol Chem 278, 25872-25878

 

  • Song, X., Lin, H. P., Johnson, A. J., Tseng, P. H., Yang, Y. T., Kulp, S. K., and Chen, C. S. (2002) Cyclooxygenase-2, player or spectator in cyclooxygenase-2 inhibitor-induced apoptosis in prostate cancer cells. J Natl Cancer Inst 94, 585-591

 

  • Lin, H., Lin, T. N., Cheung, W. M., Nian, G. M., Tseng, P. H., Chen, S. F., Chen, J. J., Shyue, S. K., Liou, J. Y., Wu, C. W., and Wu, K. K. (2002) Cyclooxygenase-1 and bicistronic cyclooxygenase-1/prostacyclin synthase gene transfer protect against ischemic cerebral infarction. Circulation 105, 1962-1969

 

  • Tseng, P. H., Jiaang, W. T., Chang, M. Y., and Chen, S. T. (2001) Facile solid-phase synthesis of an antifreeze glycoprotein. Chemistry 7, 585-590

 

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