徐立中

徐立中 Ph.D. Li-Chung Hsu

專任副教授 Associate Professor

研究領域:
分子免疫與訊息傳導
Molecular Immunity and Signal Pathway

研 究 室:
臺大醫院東址2樓分子醫學所
Institute of Molecular Medicine, 2nd Floor, Main Building(NTUH East Campus)

Tel:886-2-23123456 #65700(office) #65703(laboratory)

Our lab is focused on understanding the regulation of the innate immune response against pathogenic infection and tissue damage. Innate immune system is the first line of host defense that prevents infection and eliminates the microbes. In addition, innate immunity plays a pivotal role in initiation and determination of the adaptive immune response. Innate immune cells, such as macrophages, use pattern-recognition receptors (PRRs) to detect conserved microbial molecules termed pathogen associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) released by injured cells to induce pro-inflammatory cytokines, chemokines, interferons and upregulate co-stimulatory molecules. Apart from the beneficial effects of pro-inflammatory cytokines in promoting inflammatory cell accumulation and stimulating the antimicrobial system, an imbalance between pro- and anti-inflammatory cytokines might contribute to the pathogenesis of chronic inflammatory and infectious disease. Thus, innate immune response must be tightly regulated to avoid uncontrolled inflammation.

We have been specifically interested in studying two types of PRRs: Toll-like receptors (TLRs) and the nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs). We utilize several approaches that include molecular and cellular studies, and mouse genetic model to address our research questions. Our current research interests are aimed at elucidating 1) the molecular mechanisms of TLR signaling pathways in activated macrophages, 2) the mechanism of the inflammasome activation and IL-1b production.
 

  • 1988 BS Department of Food Science, National Chung Hsing University, Taiwan
  • 1990 MS Department of Food Science, National Chung Hsing University, Taiwan
  • 2001 PhD Department of Molecular Genetics, University of Illinois at Chicago, Chicago, USA

  • 2014-present, Associate Professor, Graduate Institute of Molecular Medicine, National Taiwan University, Taiwan
  • 2007-2014, Assistant Professor, Graduate Institute of Molecular Medicine, National Taiwan University, Taiwan
  • 2005-2007, Assistant Research Scientist, Department of Pharmacology, University of California, San Diego, USA
  • 2002-2005, Postdoctoral Fellow, Department of Pharmacology, University of California, San Diego, USA
  • 1991-1995, Research Assistant, Institute of Molecular Biology, Academia Sinica, Taiwan
  • 1990-1991, Research Assistant, Cell Biology and Immunology Division, Development Center for Biotechnology, Taiwan
     

 

實驗室成員Lab Members
●博士後研究員Postdoctoral Researcher
  賴亭諭 周志璋 巫聖揚
●研究助理Assistant Researcher
  連佳儀
●博士生PhD student
  林佳靜 張詠淇 沈家興 林祐聖
●碩士生Master student
  簡懿姍 劉亭妤 盧麒安
●大學部Undergraduate student
  許哲恩 蘇致騏 林子淵

校友Alumni
(畢業年度/學期, 目前動態)
(Graduated year/Semester, Current status)

●博士生PhD
  莊士億(102/1, 博士後研究員/長庚科技大學,Postdoctoral Researcher, Chang Gung University)
  賴亭諭(103/2, 博士後研究員/台灣大學, Postdoctoral Researcher, National Taiwan University)
  周志璋(104/2, 博士後研究員/台灣大學, Postdoctoral Researcher, National Taiwan University)
  李志元(105/1, 主治醫師/台大醫院外科部, Attending Physician, Department of Surgery, National Taiwan University Hospital)
●碩士生Master
  曾慈婷(98/1, 產品經理/中外製藥公司,Product Manager, Chugai Pharma Taiwan)
  楊邦彥(98/2, 技佐/台北市整府衛生局,Department of Health, Taipei City Goverment)
  何宜霖(99/2, 博士生/德州大學, PhD program, The University of Texas, MD Anderson Cancer Center, US)
  沈怡如(100/1, 博士生/慕尼黑大學,PhD program, University of Munich, Germany )
  許書維(100/2, 技術員/衛福部食品藥物管理署,Food and Drug Administration)
  陳俞靜(100/2, 研究員/德必碁生物科技, TBG Diagnostics)
  張綺芝(100/2, 博士後研究員/丹麥大學, Postdoctoral Reseacher, Aarhus University, Danmark)
  趙俊豪(101/2, 博士生/波士頓大學PhD program, University of Massachusetts Medical School, US)
  楊志祥(101/2, 博士生/弗萊堡大學PhD program, Max Planck Institute of Immunology and Epigenetics, Freiburg University, Germany)
  賴怡惠(102/2, 博士生/漢諾威萊布尼茲大學PhD program, Helmholtz Center for Infection Research, Leibniz University of Hanover, Germany)
  連佳儀(102/2, 研究助理/台灣大學Assistant Researcher, National Taiwan University)
  謝佑鑫(103/2, 博士生/夏綠特柏林醫學大學 PhD program, Center of Infection Biology and Immunity Graduate School, Charité Universitätsmedizin Berlin)
  蔡惠玫(103/2, 研究助理/台中榮總, Research Assistant, Taichung Veterans General Hospital)
  陳彥剴(104/2, 生物老師/桃園)
  何育信(104/2, 助理研究員/生控基因疫苗股份有限公司)
  吳苗嫻(104/2, 臨床法規專員/華鼎生技)
  楊昀芸(104/2, 學生/臺北醫學大學醫學系)
  王叔蓬(106/1, 碩士生/波士頓大學音樂學院Master Program, Boston University Master of Music/Piano    Performance)
  林鼎翔(107/2, 兵役)
  江蕙萱(107/2, 研究助理/中央研究院Assistant Researcher, Academia Sinica)
  郭湘怡(107/2, 副研究員/新鈺生技公司)
●研究助理Assistant Researcher
  葉姿汶(98-100)
  林晏如(106-107, 博士生/Paul-Ehrlich-Institut, Germany)
●大學部Undergraduate
  廖祥輝(100, Biology Teacher, ST. Peter High School)
  周沛丞(101, Department of Physical Therapy, National Taiwan University)
  許皓翔(103, Department of Medicine, National Taiwan University)
  田仲棠(106, Department of Medicine, National Taiwan University)
 

  1. Lai CY, Su YW, Lin KI, Hsu LC, and Chuang TH. (2017) Natural Modulators of Endosomal Toll-Like Receptor-Mediated Psoriatic Skin Inflammation. J Immunol Res. 2017:7807313.
  2. Chang TH, Huang JH, Lin HC, Chen WY, Lee YH, Hsu LC, Netea MG, Ting JP, and Wu-Hsieh BA. (2017) Dectin-2 is a primary receptor for NLRP3 inflammasome activation in dendritic cell response to Histoplasma capsulatum. PLoS Pathog. 13(7):e1006485.
  3. Lee CY, Lai TY, Tsai MK, Chang YC, Ho YH, Yu IS, Yeh TW, Chou CC, Lin YS, Lawrence T, and Hsu LC* (2017) The Ubiquitin Ligase ZNRF1 promotes caveolin-1 ubiquitination and degradation to modulate inflammation. Nat Commun. 8: 15502.
  4. Huang MT, Chen YL, Lien CI, Liu WL, Hsu LC, Yagita H, and Chiang BL. (2017) Notch Ligand DLL4 Alleviates Allergic Airway Inflammation via Induction of a Homeostatic Regulatory Pathway. Sci Rep. 7:43535
  5. 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
  6. Lee CY, Lai TY, Tsai MK, Ou-Yang P, Tsai CY, Wu SW, Hsu LC, Chen JS (2016) The influence of a caveolin-1 mutant on the function of P-glycoprotein. Sci Rep. 6:20486
  7. Daniel J. Klionsky and 1269 other authors including Hsu LC. (2016) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12(1):1-222
  8. 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
  9. Lee YL, Yen JJ, Hsu LC, Kuo NW, Su MW, Yang MF, Hsiao YP, Wang IJ, Liu FT (2015) Association of STAT6 genetic variants with childhood atopic dermatitis in Taiwanese population. J Dermatol Sci. 79(3):222-8
  10. 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.
  11. Chuang, S.-Y., Yang, C.-H., Chou, C.-C., Chiang, Y.-P., Chuang, T.-H., Hsu, L.-C.* (2013) TLR-induced PAI-2 expression suppresses IL-1β processing via increasing autophagy and NLRP3 degradation.  Proc Natl Acad Sci USA 110(40):16079-16084 (*correspondence)
  12. Lai, T.-Y., Wu, S.-D., Tsai, M.-H., Chuang, E.Y., Chuang, L.-L., Hsu, L.-C.*, Lai, L.-C.* (2013) Transcription of Tnfaip3 Is Regulated by NF-κB and p38 via C/EBPβ in Activated Macrophages. PLoS One. 8(9):e73153. (*correspondence)
  13. Bebien M, Hensler ME, Davanture S, Hsu, L.-C., Karin M, Park JM, Alexopoulou L, Liu GY, Nizet V, Lawrence T. (2012) The Pore-Forming Toxin β hemolysin/cytolysin Triggers p38 MAPK-Dependent IL-10 Production in Macrophages and Inhibits Innate Immunity. PLoS Pathog. 8(7):e1002812.
  14. Hsu, L.-C.*, Enzler, T., Seita, J., Timmer, A.M., Lee, C.-Y., Lai, T.-Y., Yu, G.-Y., Lai, L.-C., Temkin, V., Sinzig, U., Aung, T., Nizet, V., Weissman, I.L., and Karin, M.* (2011) Interleukin 1β-driven neutrophilia preserves preserve anti-bacterial defense in absence of IKKβ. Nature Immunology 12(2):144-50 (*correspondence)
  15. Xu, C., Liu, J., Hsu, L.-C., Luo, Y., Xiang, R., and Chuang, T.-H. (2011) Functional interaction of Hsp90 and Beclin 1 modulates Toll-like receptor mediated autophagy. FASEB Journal 25(8):2700-10
  16. Lee, C.-Y., Lai, T.-Y., Wu, Y.-M., Hu, R.-H., Lee, P.-H., Hsu, L.-C., and Tsai, M.-K. (2010) Gene expression of P-glycoprotein and cytochrome P450 3A4 in peripheral blood mononuclear cells and correlation with expression in liver. Transplant Proc. 42(3):834-6 
  17. Liu, J., Xu, C., Hsu, L.-C., Luo, Y., Xiang, R., and Chuang, T.-H. (2010) A five-amino-acid motif in the undefined region of the TLR8 ectodomain is required for species-specific ligand recognition. Molecular Immunology 47(5):1083-90
  18. Timmer, A.M., Timmer, J.C., Pence, M.A., Hsu, L.-C., Ghochani, M., Frey, T.G., Karin, M., Salvesen, G.S., and Nizet, V. (2009) Streptolysin O promotes group A Streptococcus immune evasion by accelerated macrophage apoptosis. J Biol Chem 284(2):862-71
  19. 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-1b secretion in response to Bacillus anthracis infection and muramyl dipeptide. Proc Natl Acad Sci USA 105(22):7803–7808 (*correspondence)
  20. Greten, F. G., Arkan, M.C., Bollrath, J., Hsu, L.-C., Goode, J., Miething, C., Göktuna, S.I., Neuenhahn, M., Fierer, J., Paxian, S., Rooijen, N.V., Xu, Y., O’ Cain, T., Jaffee, B.B., Busch, D.H., Duyster, J., Schmid, R.M., Eckmann, L., and Karin, M. (2007) NF-kB is a negative regulator of IL-1b secretion as revealed by genetic and pharmacological inhibition of IKKb. Cell 130(5):918-31
  21. Gerbod-Giannone, M.C., Li, Y., Holleboom, A., Han, S., Hsu, L.-C., Tabas, I., and Tall, A.R. (2006) TNFa induces ABCA1 through NF-kB in macrophages and in phagocytes ingesting apoptotic cells. Proc Natl Acad Sci USA 103(9):3112-7
  22. Häcker, H., Redecke, V., Blagoev, B., Kratchmarova, I., Hsu, L.-C., Wang, G.G., Kamps, M.P., Raz, E., Wagner, H., Häcker, G., Mann, M., and Karin, M. (2006) Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature 439(7073):204-7
  23. Ruocco, M.G., Maeda, S., Park, J.M., Lawrence, T., Hsu, L.-C., Schett, G., Wagner, E.F. and Karin, M. (2005) IkB kinase b(IKKb), but not IKKa, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss. J Exp Med 201(10):1677-87
  24. Maeda, S., Hsu, L.-C., Liu, H., Bankston, L.A., Iimura, M., Kagnoff, M.F., Eckmann, L. and Karin, M. (2005) A Nod2 mutation linked to Crohn’s disease potentiates NF-kB activation and IL-1b processing. Science 307(5710):734-8
  25. Valledor, A.V., Hsu, L.-C., Ogawa, S., Sawka-Verhelle, D., Karin, M. and Glass, C.K. (2004) Liver X Receptors inhibit macrophage proliferation and prevent bacterial-induced apoptosis. Proc Natl Acad Sci USA 101(51):17813-8 
  26. Luo, J.-L., Maeda, S., Hsu, L.-C., Yagita, H., Karin, K. (2004) Inhibition of NF-kB in cancer cells converts inflammation-induced tumor growth mediated by TNFa to TRAIL-mediated tumor regression. Cancer Cell 6(3):297-305
  27. Hsu, L.-C., Park, J.M., Zhang, K., Luo, J.-L., Maeda, S., Kaufman, R.J., Eckmann, L., Guiney, D.G., and Karin, M. (2004) The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 428(6980):341-345
  28. Hsu, L.-C., Liu, S., Abedinpour, F., Beech, R.D., Lahti, J.M., Kidd, V.J., Greenspan, J.A., and Yeung, C.-Y. (2003) The Murine G+C-rich Promoter Binding Protein mGPBP is required for promoter-specific transcription. Mol Cell Biol. 23(23):8773-85
  29. Trembley, J.H., Hu, D., Hsu, L.-C., Yeung, C.-Y., Slaughter, C., Lahti, J.M., and Kidd, V.J. (2002). PITSLRE p110 protein kinases associate with transcription complexes and affect their activity. J Biol Chem. 277(4):2589-96
  30. Yeh, J.-R., Hsu, L.-C., Chung, B.-c. (2000) Sp1-like proteins function in the transcription of human ferredoxin genes. J Biomed Sci. 7(2):144-51
  31. Hsu, N.-C., Guzov, V.M., Hsu, L.-C., Chung, B.-c. (1999) Characterization of the consequence of a novel Glu-380 to Asp mutation by expression of functional P450c21 in Escherichia coli. Biochim Biophys Acta 1430(1):95-102
  32. Hsu, L.-C., Hsu, N.-C., Guzova, J., Guzov, V., Chang, S.-F., and Chung, B.-c. (1996) The Common I172N Mutation Causes Conformational Change of Cytochrome P450c21 Revealed by Systematic Mutation, Kinetic, and structural studies. J Biol Chem. 271(6):3306-3310
  33. Hu, M.-C., Hsu, L.-C., Hsu, N.-C., and Chung, B.-c. (1996) Function and Membrane topology of wild-type and mutated cytochrome P-450c21. Biochem J. 316:325-329
  34. Hsu, L.-C., Hu, M.-C., Cheng, H.-C., Lu, J.-C., and Chung, B.-c. (1993) The N- terminal Hydrophobic Domain of P450c21 is required for Membrane Insertion and Enzyme Stability. J Biol Chem. 268(20):14682-14686

 

  1. Hsu, L.-C., and Karin, M. (2010) Methods And Compositions For Reducing Microbial Induced Apoptosis. U.S. Patent No. 7,776,527
  2. Yeung, C.-Y., Hsu, L.-C., and Liu, S. (2008) Isolated DNA encoding A GPBP polypeptide, vectors comprising such DNA, isolated GPBP polypeptides, and isolated antibodies that bind to GPBP polypeptides. Taiwan, R.O.C. New Invention patent no. I291991.
  3. Glass, C.K., Valledor, A.E., Karin, M., and Hsu, L.-C. (2007) Compounds That Prevent Macrophage Apoptosis And Uses Thereof. U.S. Patent Application No. US 11/792154 (Filed).
  4. Liu, J. J., Fu, W. –T., Hsu, L.-C., Tang, T.-K., Chen, S.-T., Lai, I. –S., and Chang, T.-H. (1991) Antibodies against Chlamydia and the process for preparing the same. Taiwan, R.O.C. New Invention patent no. 55766.