經歷

榮譽

指導學生獲獎

研究方向

(1) 泛素化 (polyubiquitination) 對於TLRs和TNFRs訊息傳導的調控
泛素化是通過泛素共價鍵結目標蛋白的Lysine residue的轉譯後的修飾，而且可以形成多種泛素化模式而具有不同生物功能。 例如，標記有Lys48連接之polyubiquitination的蛋白會經由26S蛋白酶體而降解，而Lys63連接之polyubiquitination泛素化調節著內吞、轉錄、DNA修復及訊息傳遞。我們對於泛素化如何調控下游信號（如NF-κB、MAPK、IRF和PI3K）的差異活化並導致不同的生物結果感興趣。
(2) TLR4引發的發炎反應在肝癌中的角色
先天免疫和發炎反應是腫瘤進展和生長的關鍵危險因素。 在肝臟中，慢性感染活化了NF-κB路徑，並導致誘發肝細胞癌形成和發展的因子產生。另一方面，肝細胞的感染會導致細胞死亡，進而在存活的肝細胞觸發代償性的增殖。但是，尚不清楚先天免疫與肝癌之間聯繫的分子機制。進一步了解TLR4活化的分子機制以及鑑定肝細胞癌中激活TLR4的因子可能有助於開發新的治療方法。

(1) The regulation of polyubiquitination in TLRs and TNFRs signaling
Ubiquitination, a post-translational modification, is the process to modify the lysine residue of target protein with covalent conjugation of ubiquitin, and various modes of ubiquitnation with different biological functions can be formed. For instance, substrates marked with a Lys48-linked polyubiquitin chain are targeted to 26S proteasome-mediated degradation, whereas Lys63-linked polyubiquitination serve a regulatory function in endocytosis, transcription, DNA repair and signal transduction. We are interested in how polyubiquitination regulates differential activation of downstream signalings, such as NF-kappaB, MAPK, IRF and PI3K, and lead to distinct biological outcomes.
(2) The role of TLR4-mediated inflammation in liver cancer
Innate immunity and inflammation are critical risk factors for tumor progression and growth. In the liver, chronic infections activate NF-kappaB pathway, and lead to the production of factors that stimulate progression and development of hepatocellular carcinoma. On the other hand, infections in hepatocytes cause cell death and trigger the compensatory proliferation of surviving hepatocytes. However, molecular mechanisms underlying the connection between innate immunity and liver cancer remain unclear. Further understanding of molecular mechanism of TLR4 activation and identification of the factors that activate TLR4 in HCCs might help the development of novel therapeutic approaches.

研究著作

Yeh DW, Lai CY, Liu YL, Lu CH, Tseng PH, Yuh CH, Yu GY, Liu SJ, Leng CH, Chuang TH (2017, Dec). CpG-oligodeoxynucleotides developed for grouper toll-like receptor (TLR) 21s effectively activate mouse and human TLR9s mediated immune responses. Scientific Reports, 7(1):17297.

Cheng AC, Yang KY, Chen NJ, Hsu TL, Jou R, Hsieh SL, Tseng PH (2017, Oct). CLEC9A modulates macrophage-mediated neutrophil recruitment in response to heat-killed Mycobacterium tuberculosis H37Ra. PLoS One, 12(10):e0186780.

Chuang TY, Cheng AJ, Chen IT, Lan TY, Huang IH, Shiau CW, Hsu CL, Liu YW, Chang ZF, Tseng PH, Kuo JC. (2017, Jul). Suppression of LPS-induced inflammatory responses by the hydroxyl groups of dexamethasone. Oncotarget, 8(30):49735-49748.

Chen IT, Hsu PH, Hsu WC, Chen NJ, Tseng PH. (2015, Jul). Polyubiquitination of Transforming Growth Factor β-activated Kinase 1 (TAK1) at Lysine 562 Residue Regulates TLR4-mediated JNK and p38 MAPK Activation. Scientific Reports, 5:12300-14.

Su JC, Chang JH, Huang JW, Chen PP, Chen KF, Tseng PH, Shiau CW. (2015, Feb). Copper-obatoclax derivative complexes mediate DNA cleavage and exhibit anti-cancer effects in hepatocellular carcinoma. CHEMICO-BIOLOGICAL INTERACTIONS, 228:108-13.

Su JC, Chiang HC, Tseng PH, Tai WT, Hsu CY, Li YS, Huang JW, Ko CH, Lin MW, Chu PY, Liu CY, Chen KF, and Shiau CW (2014, Dec). RFX-1-dependent activation of SHP-1 inhibits STAT3 signaling in hepatocellular carcinoma cells. CARCINOGENESIS, 35(12):2807-14.

Chuang TH, Lai CY, Tseng PH, Yuan CJ, Hsu LC (2014, Sep). Development of CpG-oligodeoxynucleotides for effective activation of rabbit TLR9 mediated immune responses. PLoS One, 9(9):e108808.

Chang YL, Chen TH, Wu YH, Chen GA, Weng TH, Tseng PH, Hsieh SL, Fu SL, Lin CH, Chen CJ, Chu CL, Chio II, Mak TW, Chen NJ. (2014, Jul). A novel TLR2-triggered signalling crosstalk synergistically intensifies TNF-mediated IL-6 induction. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 18(7):1344-57.

Su JC, Tseng PH, Hsu CY, Tai WT, Huang JW, Ko CH, Lin MW, Liu CY, Chen KF, Shiau CW (2014, Jul). RFX1-dependent activation of SHP-1 induces autophagy by a novel obatoclax derivative in hepatocellular carcinoma cells. ONCOTARGET, 5(13):4909-19.

Su JC, Tseng PH, Wu SH, Hsu CY, Tai WT, Li YS, Chen IT, Liu CY, Chen KF, Shiau CW (2014, Jul). SC-2001 Overcomes STAT3-mediated Sorafenib Resistance through RFX-1/SHP-1 Activation in Hepatocellular Carcinoma. NEOPLASIA, 16(7):595-605.

Liu J, Xu C, Liu YL, Matsuo H, Hsieh RP, Lo JF, Tseng PH, Yuan CJ, Luo Y, Xiang R, Chuang TH. (2012, Sep). Activation of rabbit TLR9 by different CpG-ODN optimized for mouse and human TLR9. COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES, 35(5):443-51.

Häcker H, Tseng PH, Karin M. (2011, Jun). Expanding TRAF function: TRAF3 as a tri-faced immune regulator. NATURE REVIEWS IMMUNOLOGY, 11(7):457-68.

Zhang W, Kater AP, Widhopf GF 2nd, Chuang HY, Enzler T, James DF, Poustovoitov M, Tseng PH, Janz S, Hoh C, Herschman H, Karin M, Kipps TJ. (2010, Nov). B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemia. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.

Tseng PH*, Matsuzawa A*, Zhang W, Mino T, Vignali DA, Karin M. (2010, Jan). Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines. NATURE IMMUNOLOGY, 11: 70-5. *Equal contribution

Vallabhapurapu S, Matsuzawa A, Zhang W, Tseng PH, Keats JJ, Wang H, Vignali DA, Bergsagel PL, Karin M. (2008, Dec). Nonredundant and complementary functions of adaptor proteins TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling. NATURE IMMUNOLOGY, 9: 1364-70.

Wang H, Matsuzawa A, Brown SA, Zhou J, Guy CS, Tseng PH, Forbes K, Nicholson TP, Sheppard PW, Häcker H, Karin M, Vignali DA. (2008, Dec). Analysis of non-degradative protein ubiquitylation with a monoclonal antibody specific for lysine 63-linked polyubiquitin. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 105:20197-202.

Matsuzawa A*, Tseng PH*, Vallabhapurapu S, Luo JL, Zhang W, Wang H, Vignali DA, Gallagher E, Karin M. (2008, Aug). Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. SCIENCE, 321: 663-8. *Equal contribution

Hsu LC, Ali SR, McGillivray S, Tseng PH, Mariathasan S, Humke EW, Eckmann L, Powell JJ, Nizet V, Dixit VM, Karin M. (2008, Jun). A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptide. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 105:7803-8.

Tseng PH, Wang YC, Weng SC, Weng JR, Chen CS, Brueggemeier RW, Shapiro CL, Chen CY, Dunn SE, Pollak M, Chen CS. (2006, Nov). Overcoming trastuzumab resistance in breast cancer cells by using a celecoxib-derived PDK-1 inhibitor. MOLECULAR PHARMACOLOGY, 70: 1534-41.

Fang YC, Wu JS, Chen JJ, Cheung WM, Tseng PH, Tam KB, Shyue SK, Chen JJ, Lin TN. (2006, Apr). Induction of prostacyclin/(PGI(2) synthase expression after cerebral ischemia-reperfusion. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 26: 491-501.

Chen CS, Weng SC, Tseng PH, Lin HP, Chen CS. (2005, Nov). Nonepigenetic effects of histone deacetylase inhibitors on Akt through reshuffling protein phosphatase-1 complexes. JOURNAL OF BIOLOGICAL CHEMISTRY, 280: 38879-87.

Tseng PH, Lin HP, Zhu J, Chen KF, Hade EM, Young DC, Byrd JC, Grever M, Johnson K, Druker BJ, Chen CS. (2005, May). Synergistic interactions between imatinib and the novel phosphoinositide-dependent kinase-1 inhibitor OSU-03012 in overcoming imatinib resistance. BLOOD, 105: 4021-27.

Lin HP, Kulp SK, Tseng PH, Yang YT, Yang CC, Chen CS, Chen CS. (2004, Dec). Growth inhibitory effects of celecoxib in human umbilical vein endothelial cells are mediated through G1 arrest via multiple signaling mechanisms. MOLECULAR CANCER THERAPEUTICS, 3: 1671-80.

Tseng PH, Lin HP, Hu H, Wang C, Zhu MX, Chen CS. (2004, Sep). The canonical transient receptor potential 6 channel as a putative phosphatidylinositol 3,4,5-trisphosphate-sensitive calcium entry system. BIOCHEMISTRY, 43: 11701-8.

Zhu J, Huang JW, Tseng PH, Yang YT, Fowble J, Shiau CW, Shaw YJ, Kulp SK, Chen CS. (2004, Jun). From the cyclooxygenase-2 inhibitor celecoxib to a novel class of 3-phosphoinositide-dependent protein kinase-1 inhibitors. CANCER RESEARCH, 64: 4309-18.

Kulp SK, Yang YT, Hung CC, Chen KF, Lai JP, Tseng PH, Fowble JW, Ward PJ, Chen CS. (2004, Feb). 3-phosphoinositide-dependent protein kinase-1/Akt signaling represents a major cyclooxygenase-2-independent target for celecoxib in prostate cancer cells. CANCER RESEARCH, 64: 1444-51.

Yang CC, Lin HP, Chen CS, Yang YT, Tseng PH, Rangnekar VM, Chen CS. (2003, Jul). Bcl-xL mediates a survival mechanism independent of the phosphoinositide 3-kinase/Akt pathway in prostate cancer cells. JOURNAL OF BIOLOGICAL CHEMISTRY, 278(28):25872-8.

Lin H, Lin TN, Cheung WM, Nian GM, Tseng PH, Chen SF, Chen JJ, Shyue SK, Liou JY, Wu CW, Wu KK. (2002, Apr). Cyclooxygenase-1 and bicistronic cyclooxygenase-1/prostacyclin synthase gene transfer protect against ischemic cerebral infarction. CIRCULATION, 105(16):1962-9.

Song X, Lin HP, Johnson AJ, Tseng PH, Yang YT, Kulp SK, Chen CS. (2002, Apr). Cyclooxygenase-2, player or spectator in cyclooxygenase-2 inhibitor-induced apoptosis in prostate cancer cells. JOURNAL OF THE NATIONAL CANCER INSTITUTE, 94(8):585-91.

Tseng PH, Jiaang WT, Chang MY, Chen ST. (2001, Feb) Facile solid phase synthesis of an antifreeze glycoprotein. Chemistry: A European Journal, 7: 585-90.

Jiaang WT, Tseng PH, Chen ST, Wang KT. (2000, Jun) Facile solid phase synthesis of YEE(GalNAcAH)3, a ligand with known high affinity for asialoglycoprotein receptors. S ynlett: 797-800.

Jiaang WT, Chang MY, Tseng PH, Chen ST. (2000, Apr) A concise synthesis of O-glycosylated amino acid building block: Using phenyl selenoglycoside as glycosyl donor. Tetrahedron Lettes, 41: 3127-30.

Chen ST, Tseng PH, Yu HM, Wu CY, Hsiao KF, Wu SH, Wang KT. (1997) The studies of microwave effects on the chemical reactions. Journal of Chinese Chemical Society, 44: 169-82.