Lewis Lanier, PhD

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Lewis Lanier, PhD

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Professor, School of Medicine
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Natural killer (NK) cells are a type of white blood cell that provides protection against microbial pathogens and tumors. Since the early 1980’s, our lab has investigated how NK cells distinguish between normal healthy cells and cells that are transformed or infected with viruses. NK cells express a diverse array of inhibitory and activating receptors on their cells surface that bind to ligands expressed on the cell surface of potential target cells. When encountering healthy cells, signals transmitted by inhibitory NK receptors dominate and prevent autoimmunity, whereas the loss of ligands for the inhibitory receptors or the upregulation of ligands for the activating NK receptors on infected or transformed cells allows NK cells to kill these abnormal cells and secrete cytokine that influence the subsequent response by T cells and B cells. We have developed mouse models systems in which key signaling molecules such as DAP10 and DAP12 have been ablated to explore the physiological role of these NK receptors in resistance to viral infections (cytomegalovirus, poxviruses, and influenza) and primary tumorigenesis.
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  1. Ogasawara K, Lanier LL. NKG2D in NK and T cell-mediated immunity. J Clin Immunol. 2005 Nov; 25(6):534-40.
  2. Humphrey MB, Daws MR, Spusta SC, Niemi EC, Torchia JA, Lanier LL, Seaman WE, Nakamura MC. TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. J Bone Miner Res. 2006 Feb; 21(2):237-45.
  3. Shiratori I, Yamaguchi M, Suzukawa M, Yamamoto K, Lanier LL, Saito T, Arase H. Down-regulation of basophil function by human CD200 and human herpesvirus-8 CD200. J Immunol. 2005 Oct 01; 175(7):4441-9.
  4. Takaki R, Hayakawa Y, Nelson A, Sivakumar PV, Hughes S, Smyth MJ, Lanier LL. IL-21 enhances tumor rejection through a NKG2D-dependent mechanism. J Immunol. 2005 Aug 15; 175(4):2167-73.
  5. Ogasawara K, Benjamin J, Takaki R, Phillips JH, Lanier LL. Function of NKG2D in natural killer cell-mediated rejection of mouse bone marrow grafts. Nat Immunol. 2005 Sep; 6(9):938-45.
  6. Lanier LL. Missing self, NK cells, and The White Album. J Immunol. 2005 Jun 01; 174(11):6565.
  7. Hamerman JA, Tchao NK, Lowell CA, Lanier LL. Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12. Nat Immunol. 2005 Jun; 6(6):579-86.
  8. Desrosiers MP, Kielczewska A, Loredo-Osti JC, Adam SG, Makrigiannis AP, Lemieux S, Pham T, Lodoen MB, Morgan K, Lanier LL, Vidal SM. Epistasis between mouse Klra and major histocompatibility complex class I loci is associated with a new mechanism of natural killer cell-mediated innate resistance to cytomegalovirus infection. Nat Genet. 2005 Jun; 37(6):593-9.
  9. Ehrlich LI, Ogasawara K, Hamerman JA, Takaki R, Zingoni A, Allison JP, Lanier LL. Engagement of NKG2D by cognate ligand or antibody alone is insufficient to mediate costimulation of human and mouse CD8+ T cells. J Immunol. 2005 Feb 15; 174(4):1922-31.
  10. Lanier LL. First sighting of the elusive T cell antigen receptor. J Immunol. 2005 Feb 01; 174(3):1143.
  11. Zingoni A, Sornasse T, Cocks BG, Tanaka Y, Santoni A, Lanier LL. NK cell regulation of T cell-mediated responses. Mol Immunol. 2005 Feb; 42(4):451-4.
  12. Hamerman JA, Ogasawara K, Lanier LL. NK cells in innate immunity. Curr Opin Immunol. 2005 Feb; 17(1):29-35.
  13. Lanier LL. NK cell recognition. Annu Rev Immunol. 2005; 23:225-74.
  14. Lanier LL. NKG2D in innate and adaptive immunity. Adv Exp Med Biol. 2005; 560:51-6.
  15. Lodoen MB, Lanier LL. Viral modulation of NK cell immunity. Nat Rev Microbiol. 2005 Jan; 3(1):59-69.
  16. Bach JF, Bendelac A, Brenner MB, Cantor H, De Libero G, Kronenberg M, Lanier LL, Raulet DH, Shlomchik MJ, von Herrath MG. The role of innate immunity in autoimmunity. J Exp Med. 2004 Dec 20; 200(12):1527-31.
  17. Lodoen MB, Abenes G, Umamoto S, Houchins JP, Liu F, Lanier LL. The cytomegalovirus m155 gene product subverts natural killer cell antiviral protection by disruption of H60-NKG2D interactions. J Exp Med. 2004 Oct 18; 200(8):1075-81.
  18. Voehringer D, Rosen DB, Lanier LL, Locksley RM. CD200 receptor family members represent novel DAP12-associated activating receptors on basophils and mast cells. J Biol Chem. 2004 Dec 24; 279(52):54117-23.
  19. Zingoni A, Sornasse T, Cocks BG, Tanaka Y, Santoni A, Lanier LL. Cross-talk between activated human NK cells and CD4+ T cells via OX40-OX40 ligand interactions. J Immunol. 2004 Sep 15; 173(6):3716-24.
  20. Meresse B, Chen Z, Ciszewski C, Tretiakova M, Bhagat G, Krausz TN, Raulet DH, Lanier LL, Groh V, Spies T, Ebert EC, Green PH, Jabri B. Coordinated induction by IL15 of a TCR-independent NKG2D signaling pathway converts CTL into lymphokine-activated killer cells in celiac disease. Immunity. 2004 Sep; 21(3):357-66.
  21. Rosen DB, Araki M, Hamerman JA, Chen T, Yamamura T, Lanier LL. A Structural basis for the association of DAP12 with mouse, but not human, NKG2D. J Immunol. 2004 Aug 15; 173(4):2470-8.
  22. Ogasawara K, Hamerman JA, Ehrlich LR, Bour-Jordan H, Santamaria P, Bluestone JA, Lanier LL. NKG2D blockade prevents autoimmune diabetes in NOD mice. Immunity. 2004 Jun; 20(6):757-67.
  23. Mócsai A, Humphrey MB, Van Ziffle JA, Hu Y, Burghardt A, Spusta SC, Majumdar S, Lanier LL, Lowell CA, Nakamura MC. The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proc Natl Acad Sci U S A. 2004 Apr 20; 101(16):6158-63.
  24. Tahara-Hanaoka S, Shibuya K, Onoda Y, Zhang H, Yamazaki S, Miyamoto A, Honda S, Lanier LL, Shibuya A. Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112). Int Immunol. 2004 Apr; 16(4):533-8.
  25. Arase H, Lanier LL. Specific recognition of virus-infected cells by paired NK receptors. Rev Med Virol. 2004 Mar-Apr; 14(2):83-93.