莊懷佳 副研究員

Dr. Huai-Chia Chuang  莊懷佳 副研究員                             Profile updated: Sept 30, 2022

Associate Investigator

Immunology Research Center, National Health Research Institutes

[Contact Information]

Phone      +886-37-206166 Ext. 37616

Fax            +886-37-586642

Email        cinth@nhri.edu.tw

Address  3F, Bldg R1, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan (R.O.C.)

   SPECIALITY & RESEARCH FIELD OF INTEREST

Dr. Chuang is interested in studying the T-cell-mediated immune responses and inflammatory disease mechanisms. Dr. Chuang demonstrated that the kinase MAP4K3 (GLK) positively regulates T-cell activation and NF-κB signaling through phosphorylating and activating PKC-θ. Recently, Dr. Chuang’s study revealed a novel subset of Th17 cells, adipose Th17 cells, and discovered a novel disease mechanism of T-cell-mediated type 2 diabetes (T2D). Dr. Chuang’s current research focuses on studying the immunometabolism in T2D.

   EDUCATIONS AND POSITIONS 

  •  B.S., Department of Botany, National Taiwan University, Taipei, Taiwan. (2001)
  •  M.S., Graduate Institute of Pathology, National Taiwan University, Taipei, Taiwan. (2003)
  •  Ph.D., Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan. (2008)
  •  Postdoctoral Fellow, Immunology Research Center, National Health Research Institutes, Taiwan. (2014)
  •  Assistant Research Fellow (Assistant Professor equivalent), Research and Development Center for Immunology,  China Medical University, Taiwan. (2015)
  • Assistant Investigator, Immunology Research Center, National Health Research Institutes, Taiwan. (2015- 2022/09)
  • Associate Investigator, Immunology Research Center, National Health Research Institutes, Taiwan. (2022/10- )

   HONORS

  • 2010           14th International Congress of Immunology, Travel Award, Kobe, Japan
  • 2012           10th Yu‐Ziang Hsu Scientific Paper Award for Bio-medical Technology (徐有庠科技論文獎).
  • 2013           National Science Council (NSC) Best Research Paper Award for Postdoctoral Fellows (國科會第一屆博士後研究人員學術著作獎)
  • 2013           15th International Congress of Immunology, Travel Award, Milano, Italy
  • 2013           Federation of Immunological Societies of Asia-Oceania (FIMSA), Travel Award for 15th ICI
  • 2016           Federation of Immunological Societies of Asia-Oceania (FIMSA), Travel Award for 16th ICI
  • 2017           President Jui-Hsiung Tsai Paper Award
  • 2018          Ta-You Wu Memorial Award from Ministry of Science and Technology
  • 2018          Professor Chen-Yuan Lee Medical Research Scholar Memorial Award
  • 2019          Ten Outstanding Young Person Award
  • 2019          American Association of Immunologists (AAI), Early Career Faculty Travel Grant

   PUBLICATIONS

  1. Chuang HC, Lay JD, Hsieh WC, Wang HC, Chang Y, Chuang SE, Su IJ. (2005) Epstein-Barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1 cytokines in the pathogenesis of hemophagocytic syndrome. Blood.10:3090-3096.
  2.  Hsieh WC, Chang Y, Hsu MC, Lan BS, Hsiao GC, Chuang HC, Su IJ. (2007) Emergence of anti-red blood cell antibodies triggers red cell phagocytosis by activated macrophages in a rabbit model of Epstein-Barr virus-associated hemophagocytic syndrome. American Journal of Pathology. 170:1629-1639.
  3. Chuang HC, Lay JD, Chuang SE, Hsieh WC, Chang Y, Su IJ. (2007) Epstein-Barr virus (EBV) latent membrane protein-1 down-regulates tumor necrosis factor-alpha (TNF-α) receptor-1 and confers resistance to TNF-α-induced apoptosis in T cells: implication for the progression to T-cell lymphoma in EBV-associated hemophagocytic syndrome. American Journal of Pathology. 170:1607-1617.
  4. Chuang HC, Lay JD, Hsieh WC, Su IJ. (2007) Pathogenesis and mechanism of disease progression from hemophagocytic lymphohistiocytosis to Epstein-Barr virus-associated T-cell lymphoma: nuclear factor-κB pathway as a potential therapeutic target. Cancer Science.98:1281-1287.
  5. Chuang HC, Wang JM, Hsieh WC, Chang Y, Su IJ. (2008) Up-regulation of activating transcription factor-5 suppresses SAP expression to activate T cells in hemophagocytic syndrome associated with Epstein-Barr virus infection and immune disorders. American Journal of Pathology.173:1397-1405.
  6. Yang JC, Teng CF, Wu HC, Tsai HW, Chuang HC, Tsai TF, Hsu YH, Huang W, Wu LW, Su IJ. (2009) Enhanced expression of vascular endothelial growth factor-A in ground glass hepatocytes and its implication in hepatitis B virus hepatocarcinogenesis. Hepatology.49:1962-1971.
  7. Chuang HC, Lan JL, Chen DY, Yang CY, Chen YM, Li JP, Huang CY, Liu PE, Wang X, and Tan TH. (2011). The kinase GLK controls autoimmunity and NF-kB signaling by activating the kinase PKC-q in T cells. Nature Immunology.12:1113-1118.

Highlighted in News & Views “PKC-θ: hitting the bull’s eye”, Nature Immunology. 12:1031-1032.

Highlighted in Science-Business eXchange (SciBX), 4:42 (Oct. 27, 2011)

Highlighted in A-IMBN Research (Dec. 27, 2011).

  1. Chen DY, Chuang HC, Lan JL, Chen YM, Hung WT, Lai KL, Tan TH. (2012) Germinal center kinase (GCK)-Like kinase (GLK/MAP4K3) expression is increased in adult-onset Still’s disease and may act as an activity marker. BMC Medicine. 10:84.
  2. Wang X, Chuang HC, Li JP, and Tan TH. (2012) Regulation of PKC-θ function by phosphorylation in T cell receptor signaling. Frontiers in Immunology.3: 197.
  3. Chen YM*, Chuang HC*, Lan JL, Hung WT, Lin YT, Gong NR, Lin WC, Lan TH, Tan TH, Chen DY. (2013) GLK overexpression in T cells as a novel biomarker of rheumatoid arthritis. Arthritis & Rheumatism.65: 2573-2582. *, co-first author with equal contribution.
  4. Yang CY, Li JP, Lan JL, Chiu LL, Chuang HC, Huang CY, Chen DY, Tan TH. (2014) Dual-specificity phosphatase 14 (DUSP14/MKP6) negatively regulates T-cell receptor signaling by inhibiting TAK1 activation. Journal of Immunology. 192:1547-1557.
  5. Li JP, Yang CY, Chuang HC, Huang PY, Chen YR, Wang X, Belmont J, and Tan TH. (2014) The phosphatase JKAP/DUSP22 inhibits T-cell receptor signaling and autoimmunity by inactivating Lck. Nature Communications.5:3618.
  6. Chuang HC, Sheu W, Lin YT, Tsai CY, Yang CY, Cheng YJ, Huang PY, Li JP, Chiu LL, Wang X, Xie M, Schneider M, and Tan TH. (2014) HGK/​MAP4K4 deficiency induces TRAF2 stabilization and Th17 differentiation leading to insulin resistance. Nature Communications.5: 4602.
  7. Chuang HC, Wang X, Tan T.-H. 2016. MAP4K family kinases in immunity and inflammation. Advances in Immunology.129:277-314.
  8. Chuang HC, JS Wang, IT Lee, W H-H. Sheu* and Tan, T.-H*. 2016. Epigenetic regulation of HGK/MAP4K4 in T cells of type 2 diabetes patients. Oncotarget. 7:10976-10989.
  9. Hsu CP, Chuang HC, Lee MC, Tsou HH, Lee LW, Li JP, Tan, T.-H*. 2016. GLK/MAP4K3 overexpression associates with recurrence risk for non-small cell lung cancer. Oncotarget. 7:41748-41757.
  10. Ho CH, Chuang HC, Wu IC, Tsai HW, Lin YJ, Sun HY, Young KC, Chiu YC, Cheng PN, Liu WC, Tan, T.-H* and Chang TT* 2016. Prediction of early hepatocellular carcinoma recurrence using germinal center kinase-like kinase. Oncotarget. 7:49765-49776.
  11. Chuang HC, YM Chen, WT. Hung, JP. Li, DY. Chen*, JL. Lan* and Tan, T.-H*. 2016. Downregulation of the phosphatase JKAP/DUSP22 in T Cells as a potential new biomarker of systemic lupus erythematosus nephritis. Oncotarget. 7:57593-57605.
  12. Chuang, HC and T.-H. Tan*. 2017. MAP4K4 and IL-6+ Th17 cells play important roles in non-obese type 2 diabetes. Journal of Biomedical Science. (Invited review) 2017. 24:4.
  13. YR Chen, HC Chou, CH Yang, HY Chen, YW Liu, TY Lin, CL Yeh, WT Chao, HH Tsou, HC Chuang and T.-H. Tan*.2017. Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration. Oncogene. 36:6509-6517. 
  14. JC Lin, YC Lee, T.-H. Tan, YC Liang, HC Chuang, YC Fann, Kory R. Johnson, YJ Lin*. 2018. RBM4-SRSF3-MAP4K4 splicing cascade modulates the metastatic signature of colorectal cancer cell. Biochim Biophys Acta Mol Cell Res. 1865:259-272.
  15. Chuang, HC andT.-H. Tan*.2018. MAP4K3 (GLK). Encyclopedia of Signaling Molecules. (Book-chapter) Pages: 1-5.
  16. Yang CY, LL Chiu, CC Chang, HC Chuang*, and T.-H. Tan*. 2018. Induction of DUSP14 ubiquitination by PRMT5-mediated arginine methylation in T-cell signaling. FASEB Journal. 2018. 32:6760-6770 [Epub ahead of print]
  17. Peng HY, YC Liang, T.-H. Tan, HC Chuang, YJ Lin and JC Lin. 2018. RBM4a-SRSF3-MAP4K4 Splicing Cascade Constitutes a Molecular Mechanism for Regulating Brown Adipogenesis. Int J Mol Sci. 2018. 19: 2646; doi: 10.3390/ijms19092646
  18. Chuang HC, CY Tsai, CH Hsueh and T.-H. Tan*. 2018. GLK-IKKβ signaling induces dimerization and translocation of the AhR-RORγt complex in IL-17A induction and autoimmune disease. Science Advances. 2018; 4: eaat5401.
  19. Chen HF, HC Chuang* and T.-H. Tan *. 2019. Regulation of dual-specificity phosphatase (DUSP) ubiquitination and protein stability. International Journal of Molecular Sciences. 20:2668. 
  20. Chuang HC, Chang CC, Teng CF, Hsueh CH, Chiu LL, Hsu PM, Lee MC, Hsu CP, Chen YR, Liu YC, Lyu PC, and T.-H. Tan*. MAP4K3/GLK promotes lung cancer metastasis by phosphorylating and activating IQGAP1. Cancer Research. 2019. 79:4978-4993.
  21. Chuang HC, ChenYM, Chen MH, Hung WT, Yang HY, Tseng TH, and T.-H. Tan*. AhR-RORγt complex is a therapeutic target for MAP4K3/GLKhighIL-17Ahigh subpopulation of systemic lupus erythematosus. FASEB Journal. 2019. 33:11469-11480.
  22. Chuang HC and TH Tan. MAP4K3/GLK in autoimmune disease, cancer, and aging. Journal of Biomedical Science. 2019. 26:82.
  23. Chuang HC and T.-H. Tan*. MAP4K family kinases and DUSP family phosphatases in T-cell signaling and systemic lupus erythematosus. Cells. 2019. 8:1433. [ Abstract ]
  24. Yang CY, HC Chuang, CY Tsai, YZ Xiao, JY Yang, RH Huang, YC Shih, T.-H. Tan*. DUSP11 Attenuates Lipopolysaccharide-Induced Macrophage Activation by Targeting TAK1. J. Immunol. 2020. 205:1644-1652.[ Abstract ]
  25. Lai CH, CC Chang, HC Chuang, T.-H. Tan, PC Lyu. Structural Insights into the Active Site Formation of DUSP22 in N-loop-containing Protein Tyrosine Phosphatases. Int. J. Mol. Sci. 2020, 21:7515. [ Abstract ]
  26. Chuang, H.C., M.H. Chen, Y.M. Chen, H.Y. Yang, Y.R. Ciou, C.H. Hsueh, C.Y. Tsai, and T.-H. Tan. 2021. BPI overexpression suppresses Treg differentiation and induces exosome-mediated inflammation in systemic lupus erythematosus. Theranostics. 11: 9953-9966. [ Abstract ]
  27. Chuang HC, Chen MH, Chen YM, Ciou YR, Hsueh CH, Tsai CY, T.-H. Tan. 2022. Induction of interferon-γ and tissue Inflammation by overexpression of eosinophil cationic protein in T cells and exosomes. Arthritis & Rheumatology. 74:92-104. [ Abstract ]
  28. Chuang, H.C., W.T. Hung, Y.M. Chen, P.M. Hsu, J.H. Yen, J.L. Lan, T.-H. Tan. 2022. Genomic sequencing and functional analyses identify MAP4K3/GLK germline and somatic variants associated with systemic lupus erythematosus. Annals of the Rheumatic Diseases. 81:243-254. [ Abstract ]Highlighted in Lupus Foundation of America, Research News” Study Identifies New Genetic Links to Lupus“, October 6, 2021. [ link ]
  29. Chi, J.N., J.Y. Yang, C.H. Hsueh, C.Y. Tsai, H.C. Chuang*, T.-H. Tan*. 2022. MAP4K3 inhibits Treg differentiation by direct phosphorylating IKKβ and inducing IKKβ-mediated FoxO1 nuclear export and Foxp3 downregulation. Theranostics. 12:5744-5760. [ Abstract ]
  30. Chuang, H.C.*, C.H. Hsueh, P.M. Hsu, R.H. Huang, C.Y. Tsai, N.H. Chung, Y. H. Chow*, T.-H. Tan*. SARS-CoV-2 spike protein enhances MAP4K3/GLK-induced ACE2 stability in COVID-19. EMBO Molecular Medicine. 2022. e15904.  [ Abstract ]
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