徐立中

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

• 2022-present, Director, Graduate Institute of Immunology, College of Medicine, National Taiwan University
• 2022-present, Professor, Institute of Molecular Medicine, College of Medicine, National Taiwan University
• 2014-2022, Associate Professor, Institute of Molecular Medicine, National Taiwan University, Taiwan
• 2007-2014, Assistant Professor, 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

Awards and Fellowships

• 2022 The outstanding research award of MOST(110年度科技部傑出研究獎)
• 2021 The outstanding immunology scholar award, The Chinese Society of Immunology, Taiwan (中華民國免疫學會傑出研究學者獎)
• 2018 The 16th Science paper award, The Far Eastern Y. Z. Hsu Science and Technology Memorial Foundation(第十六屆有庠科技論文獎-生技醫藥類)
• 2014&2017-2020 國科會補助大專校院延攬特殊優秀人才措施獎
• 2013 IUIS - Bill and Melinda GATES Foundation Travel Awards for Young Immunologists from Developing Countries
• 2012 2012 "Excellent Teaching Award" National Taiwan University (100學年度台灣大學「教學優良」獎)
• 2012 Young Scientist Award, The TienTe Lee Biomedical Foundation (第七屆永信李天德醫藥科技獎-青年科學家學術研究獎)
• 2005-2008 Career Development Award, Crohn's & Colitis Foundation of America
• 2005 Career Development Award, Tobacco-Related Disease Research Program
• 2002-2005 Postdoctoral Fellowship, Cancer Research Institute
• 1998-2001 University Fellowship, University of Illinois at Chicago
• 1994 The Excellent Researcher Award of the National Science Council, Taiwan, R.O.C. (國科會乙等獎助)

1. Lin YS, Chang YC, Chao TL, Tsai YM, Jhuang SJ, Ho YH, Lai TY, Liu YL, Chen CY, Tsai CY, Hsueh YP, Chang SY, Chuang TH, Lee CY, and Hsu LC*. (2023) The Src-ZNRF1 axis controls TLR3 trafficking and interferon responses to limit lung barrier damage. J Exp Med 220(8):e20220727
2. Kung PJ, Lai TY, Cao J, Hsu LC, Chiang TC, Ou-Yang P, Tsai CY, Tsai YF, Lin CW, Chen CC, Tsai MK, Tien YW, and Lee CY. The role of S100A9 in the interaction between pancreatic ductal adenocarcinoma cells and stromal cells. Cancer Immunol Immunother. 2022 Mar;71(3):705-718.
3. Wang YT, Liu TY, Shen CH, Lin SY, Hung CC, Hsu LC, and Chen GC. K48/K63-linked polyubiquitination of ATG9A by TRAF6 E3 ligase regulates oxidative stress-induced autophagy. Cell Rep. 2022 Feb 22;38:110354
4. Tseng JC, Chang YC, Huang CM, Hsu LC* and Chuang TH*. Therapeutic Development Based on the Immunopathogenic Mechanisms of Psoriasis. Pharmaceutics 2021 July 11;13(7):1064 (*correspondence)
5. Lin CC, Shen YR, Chang CC, Guo SY, Young YY, Lai TY, Yu IS, Lee CY, Chuang TH, Tsai HY, and Hsu LC*. (2021) Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation. Nature Commun. 12:3878
6. Shen CH, Chou CC, Lai TY, Hsu JE, Lin YS, Liu HY, Chen YK, Ho IL, Hsu PH, Chuang TH, Lee CY, and Hsu LC*. ZNRF1 mediates epidermal growth factor receptor ubiquitination to control receptor lysosomal trafficking and degradation. Front Cell Dev Biol. 2021 Apr 29;9:642625 (*correspondence)
7. Chuang YC, Tseng JC, Yang JX, Liu YL, Yeh DW, Lai CY, Yu GY, Hsu LC, Huang CM, and Chuang TH. Toll-Like Receptor 21 of Chicken and Duck Recognize a Broad Array of Immunostimulatory CpG-oligodeoxynucleotide Sequences. Vaccines (Basel). 2020 Nov 2;8(4):639.
8. Lu CH, Lai CY, Yeh DW, Liu YL, Su YW, Hsu LC, Chang CH, Jin SLC, and Chuang TH. Involvement of M1 Macrophage Polarization in Endosomal Toll-like Receptors Activated Psoriatic Inflammation. Mediators Inflamm. 2018 Dec 16; 2018:3523642
9. Chen YJ, Wang SF, Weng IC, Hong MH, Lo TH, Jan JT, Hsu LC, Chen HY, and Liu FT. Galectin-3 Enhances Avian H5N1 Influenza A Virus-Induced Pulmonary Inflammation by Promoting NLRP3 Inflammasome Activation. Am J Pathol. 2018 Apr;188(4):1031-1042.
10. Lai CY, Su YW, Lin KI, Hsu LC, and Chuang TH. Natural Modulators of Endosomal Toll-Like Receptor-Mediated Psoriatic Skin Inflammation. J Immunol Res. 2017;2017:7807313.
11. Chang TH, Huang JH, Lin HC, Chen WY, Lee YH, Hsu LC, Netea MG, Ting JP, and Wu-Hsieh BA. Dectin-2 is a primary receptor for NLRP3 inflammasome activation in dendritic cell response to Histoplasma capsulatum. PLoS Pathog. 2017 Jul 3;13(7):e1006485.
12. Lee CY, Lai TY, Tsai MK, Chang YC, Ho YH, Yu IS, Yeh TW, Chou CC, Lin YS, Lawrence T, and Hsu LC* The Ubiquitin Ligase ZNRF1 promotes caveolin-1 ubiquitination and degradation to modulate inflammation. Nat Commun. 2017 Jun 8;8:15502. (*correspondence)
13. Huang MT, Chen YL, Lien CI, Liu WL, Hsu LC, Yagita H, and Chiang BL. Notch Ligand DLL4 Alleviates Allergic Airway Inflammation via Induction of a Homeostatic Regulatory Pathway. Sci Rep. 2017 Mar 6;7:43535.
14. 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. Mycotoxin Patulin Suppresses Innate Immune Responses by Mitochondrial Dysfunction and p62/Sequestosome-1-dependent Mitophagy. J Biol Chem. 2016 Sep 9;291(37):19299-311.
15. Yeh DW, Chen YS, Lai CY, Liu YL, Lu CH, Lo JF, Chen L, Hsu LC, Luo Y, Xiang R, Chuang TH. Downregulation of COMMD1 by miR-205 promotes a positive feedback loop for amplifying inflammatory- and stemness-associated properties of cancer cells. Cell Death Differ. 2016 May;23(5):841-52.
16. Lee CY, Lai TY, Tsai MK, Ou-Yang P, Tsai CY, Wu SW, Hsu LC, Chen JS. The influence of a caveolin-1 mutant on the function of P-glycoprotein. Sci Rep. 2016 Feb 4;6:20486.
17. Daniel J. Klionsky and 1269 other authors including Hsu LC. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016 Jan 21;12(1):1-222.
18. Lee YL, Yen JJ, Hsu LC, Kuo NW, Su MW, Yang MF, Hsiao YP, Wang IJ, Liu FT.  Association of STAT6 genetic variants with childhood atopic dermatitis in Taiwanese population. J Dermatol Sci. 2015 Sep;79(3):222-8.
19. Chuang TH, Lai CY, Tseng PH, Yuan CJ, Hsu LC. Development of CpG-oligodeoxynucleotides for effective activation of rabbit TLR9 mediated immune responses. PLoS One. 2014 Sep 30;9(9):e108808.
20. Chuang SY, Yang CH, Chou CC, Chiang YP, Chuang TH, Hsu LC* TLR-induced PAI-2 expression suppresses IL-1β processing via increasing autophagy and NLRP3 degradation. Proc Natl Acad Sci USA. 2013 Oct 1;110(40):16079-16084 (*correspondence)
21. Lai TY, Wu SD, Tsai MH, Chuang EY, Chuang LL, Hsu LC*, Lai LC* Transcription of Tnfaip3 Is Regulated by NF-κB and p38 via C/EBPβ in Activated Macrophages. PLoS One. 2013 Sep 2;8(9):e73153. (*correspondence)
22. Bebien M, Hensler ME, Davanture S, Hsu LC, Karin M, Park JM, Alexopoulou L, Liu GY, Nizet V, Lawrence T. The Pore-Forming Toxin β hemolysin/cytolysin Triggers p38 MAPK-Dependent IL-10 Production in Macrophages and Inhibits Innate Immunity. PLoS Pathog. 2012;8(7):e1002812.
23. Hsu LC*, Enzler T, Seita J, Timmer AM, Lee CY, Lai TY, Yu GY, Lai LC, Temkin V, Sinzig U, Aung T, Nizet V, Weissman IL, and Karin M* Interleukin 1β-driven neutrophilia preserves preserve anti-bacterial defense in absence of IKKβ. Nat Immunol. 2011 Feb;12(2):144-50 (*correspondence)
24. Xu C, Liu J, Hsu LC, Luo Y, Xiang R, and Chuang TH. Functional interaction of Hsp90 and Beclin 1 modulates Toll-like receptor mediated autophagy. FASEB J. 2011 Aug;25(8):2700-10.
25. Lee CY, Lai TY, Wu YM, Hu RH, Lee PH, Hsu LC, and Tsai MK. Gene expression of P-glycoprotein and cytochrome P450 3A4 in peripheral blood mononuclear cells and correlation with expression in liver. Transplant Proc. 2010 Apr;42(3):834-6 .
26. Liu J, Xu C, Hsu LC, Luo Y, Xiang R, and Chuang TH. A five-amino-acid motif in the undefined region of the TLR8 ectodomain is required for species-specific ligand recognition. Mol Immunol. 2010 Feb;47(5):1083-90.
27. Timmer AM, Timmer JC, Pence MA, Hsu LC, Ghochani M, Frey TG, Karin M, Salvesen GS, and Nizet V. Streptolysin O promotes group A Streptococcus immune evasion by accelerated macrophage apoptosis. J Biol Chem. 2009 Jan 9;284(2):862-71.
28. Hsu LC*, Ali SR, McGillivray S, Tseng PH, Mariathasan S, Humke EW, Eckmann L, Powell JJ, Nizet V, Dixit VM, and Karin M* 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. 2008 Jun 3;105(22):7803-7808 (*correspondence)
29. Greten FG, Arkan MC, Bollrath J, Hsu LC, Goode J, Miething C, Göktuna SI, Neuenhahn M, Fierer J, Paxian S, Rooijen NV, Xu Y, O’ Cain T, Jaffee BB, Busch DH, Duyster J, Schmid RM, Eckmann L, and Karin M. NF-kB is a negative regulator of IL-1b secretion as revealed by genetic and pharmacological inhibition of IKKb. Cell. 2007 Sep 7;130(5):918-31.
30. Gerbod-Giannone MC, Li Y, Holleboom A, Han S, Hsu LC, Tabas I, and Tall AR. TNFa induces ABCA1 through NF-kB in macrophages and in phagocytes ingesting apoptotic cells. Proc Natl Acad Sci USA. 2006 Feb 28;103(9):3112-7.
31. Häcker H, Redecke V, Blagoev B, Kratchmarova I, Hsu LC, Wang GG, Kamps MP, Raz E, Wagner H, Häcker G, Mann M, and Karin M. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6. Nature. 2006 Jan 12;439(7073):204-7.
32. Ruocco MG, Maeda S, Park JM, Lawrence T, Hsu LC, Schett G, Wagner EF, and Karin M. 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. 2005 May 16;201(10):1677-87.
33. Maeda S, Hsu LC, Liu H, Bankston LA, Iimura M, Kagnoff MF, Eckmann L and Karin M. A Nod2 mutation linked to Crohn’s disease potentiates NF-kB activation and IL-1b processing. Science. 2005 Feb 4;307(5710):734-8.
34. Valledor AV, Hsu LC, Ogawa S, Sawka-Verhelle D, Karin M and Glass CK. Activation of liver X receptors and retinoid X receptors prevents bacterial-induced macrophage apoptosis. Proc Natl Acad Sci USA. 2004 Dec 21;101(51):17813-8.
35. Luo JL, Maeda S, Hsu LC, Yagita H, Karin K. Inhibition of NF-kB in cancer cells converts inflammation-induced tumor growth mediated by TNFa to TRAIL-mediated tumor regression. Cancer Cell. 2004 Sep;6(3):297-305.
36. Hsu LC, Park JM, Zhang K, Luo JL, Maeda S, Kaufman RJ, Eckmann L, Guiney DG, and Karin M. The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature. 2004 Mar 18;428(6980):341-345.
37. Hsu LC, Liu S, Abedinpour F, Beech RD, Lahti JM, Kidd VJ, Greenspan JA, and Yeung CY. The Murine G+C-rich Promoter Binding Protein mGPBP is required for promoter-specific transcription. Mol Cell Biol. 2003 Dec;23(23): 8773-85.
38. Trembley JH, Hu D, Hsu LC, Yeung CY, Slaughter C, Lahti JM, and Kidd VJ. PITSLRE p110 protein kinases associate with transcription complexes and affect their activity. J Biol Chem. 2002 Jan 25;277(4):2589-96.
39. Yeh JR, Hsu LC, Chung Bc. Sp1-like proteins function in the transcription of human ferredoxin genes. J Biomed Sci. 2000 Mar-Apr;7(2):144-51.
40. Hsu NC, Guzov VM, Hsu LC, Chung Bc. Characterization of the consequence of a novel Glu-380 to Asp mutation by expression of functional P450c21 in Escherichia coli. Biochim Biophys Acta. 1999 Feb 10;1430(1):95-102.
41. Hsu LC, Hsu NC, Guzova J, Guzov V, Chang SF, and Chung Bc. The Common I172N Mutation Causes Conformational Change of Cytochrome P450c21 Revealed by Systematic Mutation, Kinetic, and structural studies. J Biol Chem. 1996 Feb 9;271(6):3306-3310.
42. Hu MC, Hsu LC, Hsu NC, and Chung Bc. Function and Membrane topology of wild-type and mutated cytochrome P-450c21. Biochem J. 1996 May 15;316:325-329.
43. Hsu LC, Hu MC, Cheng HC, Lu JC, and Chung Bc. The N- terminal Hydrophobic Domain of P450c21 is required for Membrane Insertion and Enzyme Stability. J Biol Chem. 1993 Jul 15;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.