特聘研究員

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EDUCATION AND POSITIONS HELD:

• M.D., National Yang-Ming University, Taiwan, 1984
• D.Phil., University of Oxford, UK, 1992
• Postdoctoral fellow, Stanford University, USA, 1993
• Director, Institute of Clinical Medicine, National Yang-Ming University, Taiwan, 2010-2013
• Distinguished Professor, Department of Microbiology and Immunology, National Yang-Ming University, Taiwan, 2007-2013
• Professor, Department of Microbiology and Immunology, National Yang-Ming University, Taiwan, 2001-2013
• Director, Immunology Research Center, National Yang-Ming University, Taiwan, 2000-2013
• Director, Immunology Research Center, Taipei Veterans’ General Hospital, Taiwan, 2005-2013
• Adjunct Research Fellow, Academia Sinica, Taiwan, 2009-2013
• Director, IRB on Biomedical Science Research, Academia Sinica, Taiwan, 2018-2022
• Distinguished Professor, Academia Sinica, Taiwan, 2013-present
• Joint Appointment Professor, Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taiwan, 2013-present
• Adjunct Professor, National Taiwan University, Taiwan, 2014-present
• Members, IRB on Biomedical Science Research, Academia Sinica, Taiwan, 2022- present
• Joint Appointment Distinguished Investigator / Director, National Health Research Center, Taiwan, 2022-present

HONORS:

• 2021    Outstanding Research Fellow award from the Ministry of Science and Technology (科技部109年度傑出特約研究員)
• 2020    The 18^th Y. Z. Hsu Scientific Chair Professor (第十八屆有庠科技講座)
• 2013    The 8^th Session TienTe Lee Award (第八屆永信李天德卓越醫藥科技獎)
• 2012    The 16^th National Chair Professor Award, Ministry of Education (教育部第16屆國家講座)
• 2010    Outstanding Researcher Award from the National Science Council (國科會傑出獎)
• 2009    The 4^th Long-Term Award from Acer Foundation (第四屆宏碁基金會龍騰微笑得獎人)
• 2009    The 53^th Academic Achievement Award, Ministry of Education (教育部第53屆學術獎)
• 2009    Tsungming Tu Award, Taiwan Medical Society (台灣醫學會杜聰明獎)
• 2008    The 18^th Outstanding research Achievement to National Health, “Ming-Ning Wang Memorial Foundation” (第十八屆王民寧獎-傑出貢獻獎得獎人)
• 2004    The 1^st Outstanding Alumni, National Yang-Ming University (第一屆陽明大學 傑出校友)
• 2003    Outstanding Researcher Award from the National Science Council (國科會傑出獎)
• 1999    Outstanding Researcher Award from the National Science Council (國科會傑出獎)
• 1992    Irvington Medial Foundation post-doctoral fellowship ‘Robert Wood Johnson Fellow
• 1989    Oversea Research Scholarship (ORS) from the University of Oxford
• 1989    Oversea PhD studentship from the Ministry of Education, Taiwan

RESEARCH INTERESTS:

我的實驗室致力於研究微生物感染、癌症侵襲和自體免疫反應的關鍵受體，並生產抗體作為治療性藥物。由於纖維化是慢性炎症的後果，並會導致器官功能障礙，因此我們也生產免疫調節劑，將巨噬細胞分化成M2，以促進組織修復。

宿主與病原體的相互作用

1. CLEC5A和CLEC5A/TLR2複合體

我們確定CLEC5A是黃質病毒（登革熱病毒、日本腦炎病毒和茲卡病毒）的模式識別受體（PRR）。此外，CLEC5A也參與流感病毒的發炎反應。CLEC5A還與TLR2形成異構複合物來識別細菌，在“中性粒細胞外滲透網（NETs）”的形成和促炎性細胞激素的釋放中起關鍵作用。

2. CD33為B型肝炎病毒的免疫檢查點受體

我們發現CD33是乙型肝炎病毒（HBV）表面抗原上2,6唾液酸基的模式識別受體（PRR），並為慢性乙型肝炎病毒感染中的免疫檢查點受體。我們進一步生產阻斷性抗性單株抗體，用以抑制HBV誘導的免疫耐受，顯示阻斷CD33能夠增強免疫反應，以清除病毒感染和其他唾液酸引發的人類疾病。

3. CLEC2 為新冠病毒的先天免疫受體

我們發現血小板的CLEC2直接與SARS-CoV-2的刺突蛋白相互作用，並為SARS-CoV-2誘導的免疫血栓。此外，我們也生產基因重組蛋白CLEC2.Fc來抑制SARS-CoV-2誘導的肺部血栓炎症。由於肺部是主要產生血小板的器官之一，因此發展CLEC2抑制劑是未來改善血小板引發的發炎性疾病與凝血異常的新方向。

癌細胞及自我抗原的先天免疫受體及免疫檢查點受體

類似乙型肝炎病毒，癌細胞也會誘導免疫耐受，使宿主無法清除癌細胞的入侵。由於抗-PD1/PDL-1單抗的療效僅約30％，我們正在尋找對癌細胞具有作用的受體，並生成對抗性單抗以激活宿主免疫系統對抗癌細胞入侵。同時，我們也在尋找參與內源性危險訊號誘導的無菌性炎症反應的先天免疫受體及免疫檢查點受體。

SELECTED PUBLICATIONS:

• Sung PS, Sun CP, Tao MH, Hsieh SL*, 2023, “Inhibition of SARS-CoV-2-mediated thromboinflammation by CLEC2.Fc”, EMBO MOLECULAR MEDICINE, e16351, 1-16. (SCIE)
• Wang HW, Li HH, Wu SC, Tang CK, Yu HY, Chang YC, Sung PS, Liu WL, Su MP, Yu GY, Huang LR, Chen CH*, Hsieh SL*, 2023, “CLEC5A mediates Zika virus‑induced testicular damage”, JOURNAL OF BIOMEDICAL SCIENCE, 30: 12, 1-16. (SCIE)
• Sung PS, Peng YC, Yang SP, Chiu CH, Hsieh SL*, 2022, “CLEC5A is critical in Pseudomonas aeruginosa-induced NET formation and acute lung injury”, JCI INSIGHT, 7(18), e156613. (SCIE)
• Sung PS, Yang SP, Perng YC, Sun CP, Tao MH, Hsieh SL*, 2022, “CLEC5A and TLR2 are critical in SARS-CoV-2-induced NET formation and lung inflammation”, JOURNAL OF BIOMEDICAL SCIENCE, 29(1), 52. (SCIE)
• Hsu YW, Huang H CH, Huang WC, Yeh YH, Hsiao CD, Chang WC**, Hsieh SL**, 2022, “Human rs75776403 Polymorphism Links Differential Phenotypic and Clinical Outcomes to a CLEC18A p.T151M-Driven Multiomics”, JOURNAL OF BIOMEDICAL SCIENCE, 29(1), 43. (SCIE)
• Sung PS, Hsieh SL*, 2021, “C-type lectins and extracellular vesicles in virus-induced NETosis”, JOURNAL OF BIOMEDICAL SCIENCE, 28(1), 46. (SCIE)
• Tsai TY, Huang MT, Sung PS, Peng CY, Tao MH, Yang HI, Chang WC, Yang AS, Yu CM, Lin YP, Ching-Yu Bau3, Huang CJ, Pan MH, Wu CY, Hsiao CD, Yeh YH, Shiteng Duan, James C Paulson, Hsieh SL*, 2021, “Siglec-3 (CD33) is the immune checkpoint receptor in HBV infection”, JOURNAL OF CLINICAL INVESTIGATION, 131(11), 141965. (SCIE)
• Pan YG, Huang MT, P. Sekar, Huang DY, Lin WW, Hsieh SL*, 2021, “Decoy Receptor 3 Inhibits Monosodium Urate-Induced NLRP3 Inflammasome Activation via Reduction of Reactive Oxygen Species Production and Lysosomal Rupture”, FRONTIERS IN IMMUNOLOGY, 12: 638676, 1-16. (SCIE)
• Huang YL , Huang MT, Sung PS, Chou TY, Yang RB, Yang AS, Yu CM, Hsu YW, Chang WC, Hsieh SL*, 2021, “Endosomal TLR3 co-receptor CLEC18A enhances host immune response to viral infection”, Communications biology, 4(1): 229, 1-13. (SCIE)
• Hsieh SL, 2020, Lectin in Host Defense Against Microbial Infections, Advances in Experimental Medicine and Biology, 230 pages, Singapore: Springer Nature Singapore Pte Ltd.
• Sung PS, Chang WC, Hsieh SL*, 2020, “CLEC5A: A Promiscuous Pattern Recognition Receptor to Microbes and Beyond”, editor(s): (Hsieh SL), Lectin in Host Defense Against Microbial Infections, Advances in Experimental Medicine and Biology, pp. 1204: 57-73, 新加坡: Springer Nature Singapore Pte Ltd.
• Sung PS, Hsieh SL*, 2019, “CLEC2 and CLEC5A: Pathogenic Host Factors in Acute Viral Infections”, FRONTIERS IN IMMUNOLOGY, 10: 2867, 1-9. (SCIE)
• Sung PS, Huang TF, Hsieh SL*, 2019, “Extracellular vesicles from CLEC2-activated platelets enhance dengue virus-induced lethality via CLEC5A/TLR2”, NATURE COMMUNICATIONS, 10(1): 2402, 1-13. (SCIE)
• Tsai TY, Peng CY, Yang HI, Huang YL, Tao MH, Yuan SS, Lai HC, Hsieh SL*, 2018, “The human C-type lectin 18 is a potential biomarker in patients with chronic hepatitis B virus infection”, JOURNAL OF BIOMEDICAL SCIENCE, 25(1): 59, 1-10. (SCIE)
• Tsai HW, Huang MT, Wang PH, Huang BS, Chen YJ, Hsieh SL*., 2018, “Decoy receptor 3 promotes cell adhesion and enhances endometriosis development”, JOURNAL OF PATHOLOGY, 244(2), 189-202. (SCIE)
• Chen ST, Chen JW, Wu WC, Chou TY, Yang CY, Hsieh SL*, 2017, “CLEC5A is a critical receptor in innate immunity against Listeria infection”, NATURE COMMUNICATIONS, 8(1): 299, 1-13. (SCIE)
• Chiu CW, Cheng H, Hsieh SL*, 2017, “Contusion spinal cord injury rat model”, Bio-protocol, 7(12), e2337.
• Lai JH, Lin YL, Hsieh SL* , 2017, “Pharmacological intervention for dengue virus infection”, BIOCHEMICAL PHARMACOLOGY, 129, 14-25. (SCIE)
• Teng, O, Chen, ST, Hsu TL, Sia SF, Cole S, Valkenburg SA, Hsu TY, Zheng JT, Tu W, Bruzzone R, Peiris JSM, Hsieh SL*, Yen HL*, 2017, “CLEC5A-mediated enhancement of the inflammatory response in myeloid cells contributes to influenza pathogenicity in vivo”, JOURNAL OF VIROLOGY, 91(1), e01813-e01816. (SCIE)
• Tung YL, Wu MF, Wang GJ*, Hsieh SL*, 2014, “Nanostructured electrochemical biosensor for the detection of the weak binding between the dengue virus and the CLEC5A receptor”, NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 10(6), 1335-1341. (SCIE)
• Chen DY, Yao L, Chen YM, Lin CC, Huang KC, Chen ST, Lan JL*, Hsieh SL*, 2014, “A Potential Role of Myeloid DAP12-Associating Lectin (MDL)-1 in the Regulation of Inflammation in Rheumatoid Arthritis Patients”, PLoS One, 9(1): e86105, 1-11. (SCIE)
• Yang CY, Chen JB, Tsai TF, Tsai YC, Tsai CY, Liang PH, Hsu TL, Wu CY, Netea MG, Wong CH, Hsieh SL*, 2013, “CLEC4F is an inducible C-type lectin in F4/80-positive cells and is involved in alpha-galactosylceramide presentation in liver”, PLoS One, 8(6): e65070, 1-14. (SCIE)
• Wu MF, Chen ST, Hsieh SL*, 2013, “Distinct regulation of dengue virus-induced inflammasome activation in human macrophage subsets”, JOURNAL OF BIOMEDICAL SCIENCE, 20(1): 36, 1-9. (SCIE)
• Wu MF, Chen ST, Yang AH, Lin WW, Lin YL, Chen NJ, Tsai IS, Li L, Hsieh SL*, 2013, “CLEC5A is critical for dengue virus-induced inflammasome activation in human macrophages”, BLOOD, 121(1), 95-106. (SCIE)
• Chen ST, Liu RS, Wu MF, Lin YL, Chen SY, Tan DT, Chou TY, Tsai IS, Li L, Hsieh SL*, 2012, “CLEC5A regulates Japanese encephalitis virus-induced neuroinflammation and lethality”, PLOS PATHOGENS, 8(4): e1002655, 1-18. (SCIE)
• Tai SK, Chang HC, Lan KL, Lee CT, Yang CY, Chen NJ, Chou TY, Tarng DC, Hsieh SL*, 2012, “Decoy receptor 3 enhances tumor progression via induction of tumor-associated macrophages”, JOURNAL OF IMMUNOLOGY, 188(5), 2464-2471. (SCIE)
• Chen ST , Lin YL , Huang MT , Wu MF , Hsieh SL*, 2011, “Targeting C-type lectin for the treatment of flaviviral infections.”, editor(s): Albert M. Wu, The Molecular Immunology of Complex Carbohydrates-3, pp. 769-776, USA: Springer.
• Lin WW, Hsieh SL*, 2011, “Decoy receptor 3: a pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases and cancer”, BIOCHEMICAL PHARMACOLOGY, 81(7), 838-847. (SCIE)
• Lee RT, Hsu TL, Huang SK, Hsieh SL, Wong CH, Lee YC*, 2011, “Survey of immune-related, mannose/fucose-binding C-type lectin receptors reveals widely divergent sugar-binding specificities”, GLYCOBIOLOGY, 21(4), 512-520. (SCIE)
• Hsu TL, Cheng SC, Yang WB, Chin SW, Chen BH, Huang MT, Hsieh SL*, Wong CH*, 2009, “Profiling carbohydrate-receptor interaction with recombinant innate immunity receptor-Fc fusion proteins”, JOURNAL OF BIOLOGICAL CHEMISTRY, 284(50), 34479-34489. (SCIE)
• Chen CY, Yang KY, Chen MY, Chen HY, Lin MT, Lee YC, Perng RP, Hsieh SL, Yang PC, Chou TY*, 2009, “Decoy receptor 3 levels in peripheral blood predict outcomes of acute respiratory distress syndrome”, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 180(8), 751-760. (SCIE)
• Wu MF, Yang CY, Lin TL, Wang JT, Yang FL, Wu SH, Hu BS, Chou TY, Tsai MD, Lin CH, Hsieh SL*, 2009, “Humoral immunity against capsule polysaccharide protects the host from magA+ Klebsiella pneumoniae-induced lethal disease by evading Toll-like receptor 4 signaling”, INFECTION AND IMMUNITY, 77(2), 615-621. (SCIE)
• Tsai CM, Chiu YK, Hsu TL, Lin IY, Hsieh SL, Lin KI*, 2008, “Galectin-1 promotes immunoglobulin production during plasma cell differentiation”, JOURNAL OF IMMUNOLOGY, 181(7), 4570-4579. (SCIE)
• Chang PM, Chen PM, Hsieh SL, Tzeng CH, Liu JH, Chiou TJ, Wang WS, Yen CC, Gau JP, Yang MH*, 2008, “Expression of a soluble decoy receptor 3 in patients with diffuse large B-cell lymphoma predicts clinical outcome”, INTERNATIONAL JOURNAL OF ONCOLOGY, 33(3), 549-554. (SCIE)
• Hsieh SL*, 2008, “Decoy Receptor 3 (DcR3): A Pleiotropic Immunomodulator”, BLOOD, 112(3), 916-917. (SCIE)
• Chang YC, Chen TC, Lee CT, Yang CY, Wang HW, Wang CC, Hsieh SL*, 2008, “Epigenetic control of MHC class II expression in tumor-associated macrophages by decoy receptor 3”, BLOOD, 111(10), 5054-5063. (SCIE)
• Lee CS, Hu CY, Tsai HF, Wu CS, Hsieh SL, Liu LC, Hsu PN*, 2008, “Elevated serum decoy receptor 3 with enhanced T cell activation in systemic lupus erythematosus”, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 151(3), 383-390. (SCIE)
• Wang SK, Liang PH, Astronomo RD, Hsu TL, Hsieh SL, Burton DR, Wong CH*, 2008, “Targeting the carbohydrates on HIV-1: Interaction of oligomannose dendrons with human monoclonal antibody 2G12 and DC-SIGN”, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 105(10), 3690-3695. (SCIE)
• You RI, Chang YC, Chen PM, Wang WS, Hsu TL, Yang CY, Lee CT, Hsieh SL*, 2008, “Apoptosis of dendritic cells induced by decoy receptor 3 (DcR3)”, BLOOD, 111(3), 1480-1488. (SCIE)

BOOK:

• Shie-Liang Hsieh*: Lectins in Host-Pathogen Interaction (Editor, Springer Publisher, to be completed in 2018)

BOOK CHAPTER:

• Shie-Liang Hsieh* "C-Type Lectin Receptors in Immunity" Chapter 3: C-type lectin member 5A. 2016 (editor: Sho Yamasaki) Springer Publisher Ltd. ISBN 978-4-431-56015-9
• Szu-Ting Chen, Yi-Ling Lin, Ming-Ting Huang, Ming-Fang Wu, Shie-Liang Hsieh*(2011). "The Molecular Immunology of Complex Carbohydrates-3" Chapter 40: Targeting C-Type Lectin for the Treatment of Flavivirus Infections. Springer Publisher Ltd. ISBN 978-1-4419-7877-6