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Tseng, Ping-Hui
  • Education: PhD, Pharmacy, Ohio State University, USA; Post-doc, Pharmacology, University of California San Diego, USA
  • Office: R706, 7F, Tradition Medicine Building
  • Phone: 886-2-28267234
  • Email phtseng@ym.edu.tw This e-mail address is being protected from spambots. You need JavaScript enabled to view it
  • Personal Web Site
  • Research--Signal transduction and posttranslational modification; the molecular mechanisms of Toll-like receptors and TNF receptors.
  • 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.

  • Publications
      • 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, 585-91.

      • Lin, H., Lin, T.-N., Cheung, W.-M., Nian, G.-M., Tseng, P.-H., Chen, C.-F., Chen, J.-J., Shyue, S.-K., 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, 1962-9.

      • 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, 25872-8.

      • 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, 1444-51.

      • 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, 4309-18.

      • 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, 11701-8.

      • 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, 1671-80.

      • Tseng, P.-H., Lin, H.-P., Chen, K.-F., Byrd, J. C., Michael G., Druker, B. J., and Chen, C.-S. (2005) Synergistic interactions between imatinib and the novel phosphoinositide-dependent kinase-1 inhibitor OSU-03012 in overcoming imatinib resistance. Blood 105, 4021-27.

      • Chen, C.-S., Weng, S.-C., Tseng, P.-H., Lin, H.-P., Chen, C.-S. (2005) Nonepigenetic effects of histone deacetylase inhibitors on Akt through reshuffling protein phosphatase-1 complexes. J. Biol. Chem. 280, 38879-87.

      • 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/(PGI(2) synthase expression after cerebral ischemia-reperfusion. J. Cereb. Blood Flow & Metab. 26, 491-501.

      • Tseng, P.-H., Weng, S.-C., Weng, J.-R., Brueggemeier, R. W., Shapiro, C. L., Dunn, S. E., Pollak, M., and Chen. C.-S. (2006) Overcoming trastuzumab resistance in breast cancer cells by using a celecoxib-derived PDK-1 inhibitor. Mol. Phamacol. 70, 1534-41.

      • 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., 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, 7803-8.

      • Matsuzawa, A.*, Tseng, P.-H.*, Vallabhapurapu, S., Luo, J. L., Zhang, W., Wang, H., Vignal, D. A., Gallagher, E., Karin, M. (2008) Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. Science 321, 663-8. (* equal contribution)

      • Vallabhapurapu, S., Matsuzawa, A., Zhang, W., Tseng, P.-H., Keats, J. J., Wang, H, Vignal, D. A., Bergsagel, P. L., Karin, M. (2008) Nonredundant and complementary functions of adaptor proteins TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kB signaling. Nat. Immunol. 9, 1364-70.

      • Wang, H., Matsuzawa, A., Brown, S., Zhou, J., Guy, C., Tseng, P.-H., Forbes, K., Nicholson, T., Sheppard, P., Haecker, H., Karin, M., Vignali, D. A. (2008) Analysis of non-degradative protein ubiquitylation with a monoclonal antibody specific for lysine 63-linked polyubiquitin. Proc. Natl. Acad. Sci. U S A 105, 20197-202.

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