Weiming Yuan, PhD

Title(s)Associate Professor of Molecular Microbiology and Immunology
SchoolKeck School of Medicine of USC
Phone+1 323 442 7938
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    Collapse Biography 
    Collapse Education and Training
    Fudan University, Shanghai, ChinaB.S.07/1989Biochemistry
    University of Texas at Austin, Austin, TXPh.D.08/2000Molecular Biology

    Collapse Overview 
    Collapse Overview
    NKT cells are an unconventional subset of T cells co-expressing T-cell receptor (TCR) and typical surface receptors for NK cells. In contrast to conventional adaptive T cells and B cells, NKT cells have features of both innate and adaptive arms of immune systems. Over the last several decades, NKT cells have been found to influence diverse immune responses, including immunity to infectious diseases and tumor, autoimmune diseases and allergies. Although the exact function of NKT cells during various immune responses remains elusive, recent studies have suggested that NKT cells may have been evolved primarily for their role in antimicrobial immune responses. Most NKT cells express identical or similar T cell receptors and are often called invariant NKT cells or iNKT cells. Distinct from conventional CD4+ and CD8+ T cells, iNKT cells can be activated by either exogenous or endogenous lipid ligands. In some bacterial infection, bacteria-derived exogenous lipid ligands can be directly recognized by iNKT cell TCR. In most other bacterial or viral infection, dendritic cell-derived cytokines and endogenous lipid ligands are sufficient to activate iNKT cells. During immune responses, NKT cells are rapidly activated to produce cytokines such as g-interferon (IFN-g) and IL-4, and their activation plays a key role in the development and regulation of adaptive immune responses to microbes.

    Due to the critical antiviral roles of NKT cells, herpes viruses have evolved strategies to antagonize this function. In vivo, NKT cells are mostly activated by lipid antigen presentation by CD1d. Previously, our studies have shown that herpes simplex virus-1 (HSV-1), a common herpes virus in humans, has evolved to down-regulate CD1d expression in antigen-presenting cells and thereby inhibiting NKT cell activation (Yuan, W. et al., Nature Immunol. 2006, 7, 835-842). Dissecting the molecular mechanism of HSV-1 evasion of CD1d antigen presentation and NKT cell function will provide novel targets for antiviral designs to improve the care for patients already latently infected with HSVs. Furthermore to break down the viral immune evasion mechanism will help to improve the immunogenecity and therefore the protection efficiency of vaccine candidates to prevent new infections. We have recently identified a HSV-1 protein kinase, US3, that collaborates with viral glycoprotein B to down-regulate CD1d expression in antigen presenting cells by suppressing CD1d recycling (Rao, P. et al., J. Virol. 2011, 85: 8093-8104; Ran, X. et al., J. Virol. 2015, 89: 6646-6655). Currently we are pursuing how US3, through its kinase activity, modulates CD1d recycling pathway at both molecular and cellular levels. Remarkably, while US3-difficient virus grows well in vitro, its replication is severely attenuated in vivo, suggesting that the evasion of the CD1d-restricted NKT cell function plays a critical role in viral pathogenesis.

    An emerging research field in my lab is human-specific CD1d/NKT antigen presentation. Despite a high degree of conservation, subtle but important differences exist between the CD1d antigen presentation pathways of humans and mice. These differences may account for the minimal success of natural killer T (NKT) cell-based antitumor therapies in human clinical trials, which contrast strongly with the powerful antitumor effects in conventional mouse models. In order to study human-specific CD1d antigen presentation pathway in vivo, we have recently generated novel mouse models with CD1d/NKT system humanized (Wen, X., et al., Proc. Natl. Acad. Sci. USA 2013, 110: 2963-2968; Wen, X., et al., J. Immunol. 2015, 195: 1459-1469). Characterization of these new models and application of the models to anti-tumor research are currently ongoing.

    Collapse Research 
    Collapse Research Activities and Funding
    Herpes simplex virus-1 evasion of CD1d antigen presentation pathway
    NIH/NIAID R01AI091987May 10, 2012 - Apr 30, 2017
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Rao P, Wen X, Lo JH, Kim S, Li X, Chen S, Feng X, Akbari O, Yuan W. Herpes simplex virus-1 specifically targets human CD1d antigen presentation to enhance its pathogenicity. J Virol. 2018 Sep 05. PMID: 30185591.
      View in: PubMed
    2. Wu J, Yuan W, Li J, Zhao Y, Li J, Li Z, Li C. Effects of Mild Hypothermia on Cerebral Large and Small Microvessels Blood Flow in a Porcine Model of Cardiac Arrest. Neurocrit Care. 2017 Oct; 27(2):297-303. PMID: 28405859.
      View in: PubMed
    3. Yuan W, Wu JY, Zhao YZ, Li J, Li JB, Li ZH, Li CS. Effect of mild hypothermia on renal ischemia/reperfusion injury after cardiopulmonary resuscitation in a swine model. Acta Cir Bras. 2017 Jul; 32(7):523-532. PMID: 28793036.
      View in: PubMed
    4. Yuan W, Wu JY, Zhao YZ, Li J, Li JB, Li ZH, Li CS. Comparison of early sequential hypothermia and delayed hypothermia on neurological function after resuscitation in a swine model. Am J Emerg Med. 2017 Nov; 35(11):1645-1652. PMID: 28521971.
      View in: PubMed
    5. Zhao J, Zeng Y, Xu S, Chen J, Shen G, Yu C, Knipe D, Yuan W, Peng J, Xu W, Zhang C, Xia Z, Feng P. A Viral Deamidase Targets the Helicase Domain of RIG-I to Block RNA-Induced Activation. Cell Host Microbe. 2016 Dec 14; 20(6):770-784. PMID: 27866900.
      View in: PubMed
    6. Zhang J, Feng H, Zhao J, Feldman ER, Chen SY, Yuan W, Huang C, Akbari O, Tibbetts SA, Feng P. I?B Kinase e Is an NFATc1 Kinase that Inhibits T Cell Immune Response. Cell Rep. 2016 07 12; 16(2):405-418. PMID: 27346349.
      View in: PubMed
    7. Skeate JG, Porras TB, Woodham AW, Jang JK, Taylor JR, Brand HE, Kelly TJ, Jung JU, Da Silva DM, Yuan W, Kast WM. Herpes simplex virus downregulation of secretory leukocyte protease inhibitor enhances human papillomavirus type 16 infection. J Gen Virol. 2016 Feb; 97(2):422-34. PMID: 26555393.
      View in: PubMed
    8. Seo GJ, Yang A, Tan B, Kim S, Liang Q, Choi Y, Yuan W, Feng P, Park HS, Jung JU. Akt Kinase-Mediated Checkpoint of cGAS DNA Sensing Pathway. Cell Rep. 2015 Oct 13; 13(2):440-9. PMID: 26440888; PMCID: PMC4607670.
    9. Wen X, Kim S, Xiong R, Li M, Lawrenczyk A, Huang X, Chen SY, Rao P, Besra GS, Dellabona P, Casorati G, Porcelli SA, Akbari O, Exley MA, Yuan W. A Subset of CD8aß+ Invariant NKT Cells in a Humanized Mouse Model. J Immunol. 2015 Aug 15; 195(4):1459-69. PMID: 26157173; PMCID: PMC4530047.
    10. Xiong R, Rao P, Kim S, Li M, Wen X, Yuan W. Herpes Simplex Virus 1 US3 Phosphorylates Cellular KIF3A To Downregulate CD1d Expression. J Virol. 2015 Jul; 89(13):6646-55. PMID: 25878107; PMCID: PMC4468489.
    11. Lawrenczyk A, Kim S, Wen X, Xiong R, Yuan W. Exploring the Therapeutic Potentials of iNKT Cells for Anti-HBV Treatment. Pathogens. 2014 Jul 03; 3(3):563-76. PMID: 25438012; PMCID: PMC4243429.
    12. Wen X, Xiong R, Dai Z, Kim S, Lawrenczyk A, Yuan W. Humanizing mice for the identification of novel anticancer lipids targeting iNKT cells. Oncoimmunology. 2013 Aug 01; 2(8):e25475. PMID: 24179706.
      View in: PubMed
    13. Wen X, Rao P, Carreño LJ, Kim S, Lawrenczyk A, Porcelli SA, Cresswell P, Yuan W. Human CD1d knock-in mouse model demonstrates potent antitumor potential of human CD1d-restricted invariant natural killer T cells. Proc Natl Acad Sci U S A. 2013 Feb 19; 110(8):2963-8. PMID: 23382238; PMCID: PMC3581944.
    14. Rao P, Pham HT, Kulkarni A, Yang Y, Liu X, Knipe DM, Cresswell P, Yuan W. Herpes simplex virus 1 glycoprotein B and US3 collaborate to inhibit CD1d antigen presentation and NKT cell function. J Virol. 2011 Aug; 85(16):8093-104. PMID: 21653669.
      View in: PubMed