Education Research Members in Lab Publications
1995.9-2000.7 陽明大學微免所 博士
1994.9-1995.7 陽明大學微免所 碩士班直升
1990.9-1994.6 私立台北醫學院醫技系 學士研究
2007.12-now 陽明大學微免所 助理教授
2002.3-2007.12 加拿大多倫多大學安大略腫瘤研究所 博士後研究及助理研究員
2000.8-2002-1 陽明大學微免所 博士後研究
The main focus of our research is to elucidate the modulating mechanisms of inflammatory responses. In the past few years, we have generated several knockout mouse models for dissecting the inflammatory regulation.
My laboratory in National Yang-Ming University was formally established since the end of December in 2007. In the past year, we have re-colonized the established knockout mouse models in Taipei (including C5L2, TREM1, TREM2, TREM3 and TRADD knockout lines). We also have collected many important knockout lines (including TNF, TNFRI, TNFR2, STAT1, C5aR, C3aR and DAP12 knockout mice) from other groups that will be used as controls in our research. Several analysis systems (auto-MACSTM cell isolation, automatic CountessTM cell counter, FACS analysis, cytokine ELISA and MX3000P quantitative real-time RT-PCR, luciferase reporter assay, Confocal microscopy and FRET analysis systems) had been established in our laboratory. Besides, we also established several gene expression vectors that contain the coding regions of genes involved in TNFR, TLR and C5a-mediated signaling pathways for dissecting the details in biological mechanisms. Furthermore, several in vitro and in vivo stimulation and disease models (including TLR- and bacteria-induced septic shock, MSU-induced inflammation (for gout study), collagen-induced arthritis and models on tumor-induced MDSC) are under test now which will be further applied in the available knockout mice models.
Currently there are three Ph.D. students, four master students and one technician work in our laboratory. Several ongoing projects are in progress in my laboratory. Basically we focus on three independent topics related to the inflammation regulation of innate immunity. In the first topic, we work on dissecting the mechanisms involved C5L2 in C5a-mediated responses and signaling. Our preliminary results demonstrate C5L2 interacts with C5aR, form the receptor complex in cells and mediate the optimal C5a-induced signals. We currently work on dissecting the cross-talking effects of C5L2 deficiency on C5aR and TLR signaling. It has been suggested that C5a-C5aR mediated signaling is important in MDSC cell development which play intriguing but unclear tumor protection effects. Whether C5L2 and C3aR also play roles in modulating tumor progression remains unclear and will be an intriguing future direction for us. In the second topic, we focus on study of members of TREM family. We have established TREM1, TREM2, TREM3 and DAP12 deficient models in our laboratory. The effects of TREMs and DAP12 deficiency on TLR-mediated signaling are under comprehensive analysis. The role of TREM-1 in neutrophils survival is under determined. We also generated several TREM/Fc fusion proteins for ligand-expressing cells screening. Currently we have made some progress on detecting TREM ligand(s) expression on platelets. Besides, we have established the MSU-induced inflammation model to determine the role of TREMs in the pathogenesis of gout-like diseases. Further analysis on inflammasome activation in TREM deficient mice will be an intriguing direction for us. In the third topic, we work on clarifying the signaling roles of TRADD in TLR4-mediated, MyD88-dependent and TRIF-dependent pathways. Our preliminary results demonstrated TRADD plays different roles in MyD88-dependent and in TRIF-dependent signaling. We also found an intriguing link between TIR domain of TLRs and the TRADD-mediated NF-kB activation. Whether TLRs signaling would interfere in TNFR signaling remains unclear and is under dissecting now.
Taken together, we established several useful gene deficient mouse models and several important analysis systems on analyzing the innate immune responses. In collaboration with several well-established research teams both in basic and in clinical fields, we would like to make our contributions to understand the inflammation modulating mechanisms that might play roles in the pathogenesis of infectious diseases or autoimmune diseases.
Members in our Laboratory
陳冠安 (2007 9 - 2009 7)
徐偉展 (2007 9 - 2009 7)
吳逸修 (2008 9 - 2010 7)
王慧玲 (2008 9 - 2010 7)
張育齡 (2009 9 - now)
林宣榮 (2009 9 - now)
陳慈徽 (2010 9 - now)
李偉如 (2010 9 - now)
曾凱雩 (2008 9 - now)
方誠傑 (2008 9 - now, join our lab since 2009)
徐偉展 (2009 9 - now)
曹雯珊 (2009 01 - now, VGH)
1. Hsieh SL, Chen NJ, Tarbell K, Liao NS, Lee KS, Lai YG, Lee KM., Lee KH, Wu SC, Sytwu HK, Han SH, McDevitt H. Transgenic Mice Expressing Surface Markers for IFN-g and IL-4 Producing Cells. (2000) Molecular Immunology 37, 281-293. (shared first author)
2. Yang S, Huang C, Chen NJ, Chou C, Lin C. Functional implication of human Serine/ Threonine kinase, hAIK, in cell cycle progression. (2000) Journal of Biomedical Science 7, 484-493.
3. Chen NJ, Huang MW, Hsieh SL. Enhanced Secretion of Interferon-gamma by Activated Th1 Cells Occurs via Reverse Signaling through TRANCE. (2001) Journal of Immunology 166, 270-276.
4. Hsu PN, Lin HH, Tu CF, Chen NJ, Wu KM, Tsai HF, Hsieh SL. Human FasL gene does not induce inflammation in pancreas but is unable to protect islet graft from transplantation rejection in pancreas-specific hFasL transgeneic mice. (2001) Journal of Biomedical Science 8, 262-269.
5. Hung SC, Chen NJ, Hsieh SL, Li H, Ma HL, Lo WH. Isolation and characterization of size-sieved stem cells from human bone marrow. (2002) Stem Cells 20, 249-258.
6. Suzuki N, Chen NJ, Millar DG, Suzuki S, Horacek T, Hara H, Bouchard D, Nakanishi K, Penninger JM, Ohashi PS, Yeh WC. IL-1 receptor-associated kinase 4 is essential for IL-18-mediated NK and Th1 cell responses. (2003) Journal of Immunology 170, 4031-4035.
7. Takada H, Chen NJ, Mirtsos C, Suzuki S, Suzuki N, Wakeham A, Mak TW, Yeh WC. Role of SODD in regulation of tumor necrosis factor responses. (2003) Molecular and Cellular Biolology 23, 4026-4033.
8. Yeh WC, Chen NJ. Immunology: another toll road. (2003) Nature 424, 736-737.
9. Suzuki N, Suzuki S, Eriksson U, Hara H, Mirtosis C, Chen NJ, Wada T, Bouchard D, Hwang I, Takeda K, Fujita T, Der S, Penninger JM, Akira S, Saito T, Yeh WC. IL-1R-associated kinase 4 is required for lipopolysaccharide-induced activation of APC. (2003) Journal of Immunology 171, 6065-6071.
10. Chang YC, Hsu TL, Lin HH, Chio CC, Chiu AW, Chen NJ, Lin CH, Hsieh SL. Modulation of macrophage differentiation and activation by decoy receptor 3. (2004) Journal of Leukocyte Biology 75, 486-494.
11. Chen NJ, Yeh WC. Adaptor proteins in death receptor signaling. (2005) Death Receptors in Cancer Therapy, Chapter 5, 93-109. (Humana Press, Totota, NJ, ISBN 1-58829-172-3 E-ISBN; 1-59259-851-X)
12. Cheung H, Chen NJ, Cao Z, Ono N, Ohashi PS, Yeh WC. Accessory protein-like is essential for IL-18-mediated signaling. (2005) Journal of Immunology 174, 5351-5357. (shared first author)
13. Chau H, Wong V, Chen NJ, Lin WJ, Huang HL, Mirtsos C, Bonnard M, Elford AR, Wakeham A, Itie YTA, Lemmers B, Salmena L, Pellegrini M, Hakem R, Mak TW, Ohashi PS, Yeh WC. Cellular FLICE-inhibitory protein (cFLIP) is required for T cell survival and cycling. (2005) Journal of Experimental Medicine 202, 405-413.
14. Suzuki N, Suzuki S, Millar DG, Unno M, Hara H, Calzascia T, Yamasaki S, Yokosuka T, Chen NJ, Elford AR, Suzuki JI, Takeuchi A, Mirtsos C, Bouchard D, Ohashi PS, Yeh WC, Saito T. Acritical role for the innateimmune signaling molecular IRAK-4 in T cell activation (2006), Science 311, 1927-1932.
15. Chen NJ, Mirtsos C, Suh D, Lu YC, Lin WJ, McKerlie C, Lee T, Baribault H, Tian H, Yeh WC. C5L2/GPR77 is critical for the biological activities of the anaphylatoxins C5a and C3a. (2007), Nature 446, 203-207.16. Chen NJ, Chio IIC, Lin WJ, Duncan G, Chau H, Katz D, Huang HL, Pike KA, Hao Z, Su YW, Yamamoto K, de Pooter RF, Zu´ n˜ iga-Pflu¨ cker JC, Wakeham A, Yeh WC and Mak TW. Beyond tumor necrosis factor receptor: TRADDsignaling in toll-like receptors. (2008 Aug), Proceedings of the National Academy of Sciences USA 105:12429-12434.
17. Hao Z, Duncan G, Su YW, Seagal J, Hong C, Haight J, Chen NJ, Elia A, Wakeham A, Li WY, Liepa J, Wood GA, Casola A, Rajewsky K and Mak TW. Fas expression in germinal center B cells is essential for T and B lymphocyte homeostasis. (2008 Oct), Immunity 29:1-13.
18. Kim I, Murakami K, Chen NJ, Saibil S, Matysiak-Zablocki E, Elford A, Bonnard M, Benchimol S, Jurisicova A, Yeh WC, Ohashi PS. DNA damage- and stress-induced apoptosis occurs independently of PIDD. (2009) Apoptosis 2009 Jul 3. [Epub ahead of print]
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