呂春敏老師(Chuen-Miin Leu)

Updated: 2021/9/29 National Yang-Ming University
         

      副教授 

     分機:67296

      e-mail:cmleu@nycu.edu.tw
NAME

Chuen-Miin Leu

 POSITION TITLE/AFFILIATIONS

Associate professor, Institute of Microbiology and Immunology, National Yang-Ming University
EDUCATION/TRAINING
INSTITUTION AND LOCATION DEGREE

(if applicable)

 YEAR(s) FIELD OF STUDY
Institute of Microbiology and Immunology, National Yang-Ming University PhD 1994-2000 Cancer biology
Institute of Microbiology and Immunology, National Yang-Ming University M. S. 1992-1994 Cancer biology
Department of Zoology, National Taiwan University B. S. 1988-1992 Zoology
  1. Current Research (Maximum 500 words)

B cell activation is the first step of the humoral response. After encounter cognate antigens, B cells undergo activation, proliferation, and then differentiation to become memory or plasma cells. In addition to fighting against infection, B cells play an important role in the pathogenesis of many autoimmune diseases. We are interesting in identifying novel molecules in the regulation of B cell activation and humoral response. Cytotoxic T-lymphocyte-associated antigen-4-Ig (CTLA-4-Ig) competes with CD28 for binding CD80/CD86 on antigen presenting cells (APCs) to limit T cell activation. B cells are important APCs in the pathogenesis of autoimmune diseases and express CD80/CD86 after activation; however, little is known about the effect of CTLA-4-Ig on B cells. Using purified human B cells from healthy donors, we found that CTLA-4-Ig directly suppressed Staphylococcus aureus-induced B cell activation in vitro. These results suggest that CTLA-4-Ig binding to CD80/CD86 may induce signaling in human B cells to suppress B cell activation. In patients with rheumatoid arthritis (RA), CTLA-4-Ig treatment obstructs the availability of CD80 and CD86 on the surface of the memory B cells. Interestingly, the surface levels of CD80/CD86 on the patients’ memory B cells positively correlated with disease activity, indicating that blocking CD80/CD86 on B cells by CTLA-4-Ig may hinder T cell activation and associated with the disease activity of RA in vivo.

Deltex1 (DTX1) is an E3 ligase and DTX1 knockout mice exhibit hyperactivation of T cells and lupus-like autoimmune syndromes; however, the association of DTX1 with human autoimmune diseases is totally unknown. We found that silencing of DTX1 expression enhanced interferon-γ secretion by human T cells. The expression of DTX1 in peripheral blood mononuclear cells (PBMCs) was significantly lower in 100 SLE patients than that in 50 age- and sex-matched healthy controls. Intriguingly, low DTX1 level in T cells led to high interferon-γ production in SLE patients and had a correlation with severe disease activity. In addition, low DTX1 expression in the SLE patients was associated with active lupus nephritis, lung involvement, or hypocomplementemia. Therefore, DTX1 suppressed IFN-g production by human T cells and its level is significantly lower in PBMCs from SLE patients. Deltex1 level inversely correlated with disease activity, thus it is a good marker for the onset of SLE.

  1. Positions and Honors.

Positions and Employment

2005~2014 Assistant professor, Institute of Microbiology and Immunology, National Yang-Ming University

2001~2004 Postdoctoral fellow, Division of Developmental & Clinical Immunology, Department of Medicine, University of Alabama at Birmingham, USA

2000~2001 Postdoctoral fellow, Department of Medical Research and Education, Veterans General Hospital, Taipei

 

  1. Selected Publications in the past 5 years(2017.08.01~2021.09.29)
  2. Wei CW, Lee CY, Lee DJ, Chu CF, Wang JC, Wang TC, Jane WN, Chang ZF, Leu CM, Dzhagalov IL, Hsu CL. 2018. Equilibrative nucleoside transporter 3 regulates T cell homeostasis by coordinating lysosomal function with nucleoside availability. Cell Rep. 23(8):2330-2341. doi: 10.1016/j.celrep.2018.04.077. (SCI). (Impact factor: 8.032; Rank: 14.47%)
  3. Hsu WC, Chen MY, Hsu SC, Huang LR, Kao CY, Cheng WH, Pan CH, Wu MS, Yu GY, Hung MS, Leu CM, Tan TH, Su YW. 2018. DUSP6 mediates T cell receptor-engaged glycolysis and restrains TFH cell differentiation. Proc Natl Acad Sci U S A. 115(34):E8027-E8036. doi: 10.1073/pnas.1800076115.  (SCI). (Impact factor: 9.58; Rank: 9.42%)
  4. Leu CM, Hsu TS, Kuo YP, Lai MZ, Liu PC, Chen MH, Chang DM, Tsai CY, Chen MH. 2019. Deltex1 suppresses T cell function and is a biomarker for diagnosis and disease activity of systemic lupus erythematosus. Rheumatology 58(4):719-728 (SCI). (Impact factor: 5.149; Rank: 11.29%)
  5. Liao HC, Chou YJ, Lin CC, Liu SH, Oswita A, Huang YL, Wang YL, Syu JL, Sun CM, Leu CM, Lin CH, Fu SL. 2019. Andrographolide and its potent derivative exhibit anticancer effects against imatinib-resistant chronic myeloid leukemia cells by downregulating the Bcr-Abl oncoprotein. Biochem Pharmacol. 163:308-320. doi: 10.1016/j.bcp.2019.02.028. (SCI).
  6. Liu PC, Ssu CT, Tsao YP, Liou TL, Tsai CY, Chou CT, Chen MH＊, Leu CM＊. Cytotoxic T-lymphocyte-associated antigen-4-Ig (CTLA-4-Ig) suppresses Staphylococcus aureus-induced CD80, CD86, and pro-inflammatory cytokine expression in human B cells. Arthritis Res Ther. 22(1):64. doi: 10.1186/s13075-020-2138-x. (SCI). (Impact factor: 4.148; Rank: 27.42%) Co-corresponding author.
  7. Hsu KH, Wei CW, Su YR, Chou T, Lin YL, Yang FC, Tsou AP, Hsu CL, Tseng PH, Chen NJ, Jeng KS, Leu CM＊. Upregulation of RelB in the miR-122 knockout mice contributes to increased levels of proinflammatory chemokines/cytokines in the liver and macrophages. Immunol Lett. Jul 2:S0165-2478(20)30346-1. doi: 10.1016/j.imlet.2020.06.015. (SCI) (Impact factor: 2.552; Rank: 70.57%). Corresponding author.