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. Buhtoiarov IN, Rakhmilevich AL, Lanier LL, Ranheim EA, Sondel PM. Naive mouse macrophages become activated following recognition of L5178Y lymphoma cells via concurrent ligation of CD40, NKG2D, and CD18 molecules. J Immunol. 2009 Feb 15; 182(4):1940-53.
  2. Sun JC, Beilke JN, Lanier LL. Adaptive immune features of natural killer cells. Nature. 2009 Jan 29; 457(7229):557-61.
  3. Lanier LL. DAP10- and DAP12-associated receptors in innate immunity. Immunol Rev. 2009 Jan; 227(1):150-60.
  4. Sun JC, Lanier LL. The Natural Selection of Herpesviruses and Virus-Specific NK Cell Receptors. Viruses. 2009; 1(3):362.
  5. Sun JC, Lanier LL. Cutting edge: viral infection breaks NK cell tolerance to "missing self". J Immunol. 2008 Dec 01; 181(11):7453-7.
  6. Kim CC, Parikh S, Sun JC, Myrick A, Lanier LL, Rosenthal PJ, DeRisi JL. Experimental malaria infection triggers early expansion of natural killer cells. Infect Immun. 2008 Dec; 76(12):5873-82.
  7. Saether PC, Westgaard IH, Hoelsbrekken SE, Benjamin J, Lanier LL, Fossum S, Dissen E. KLRE/I1 and KLRE/I2: a novel pair of heterodimeric receptors that inversely regulate NK cell cytotoxicity. J Immunol. 2008 Sep 01; 181(5):3177-82.
  8. Sun JC, Lanier LL. Tolerance of NK cells encountering their viral ligand during development. J Exp Med. 2008 Aug 04; 205(8):1819-28.
  9. Rosen DB, Cao W, Avery DT, Tangye SG, Liu YJ, Houchins JP, Lanier LL. Functional consequences of interactions between human NKR-P1A and its ligand LLT1 expressed on activated dendritic cells and B cells. J Immunol. 2008 May 15; 180(10):6508-17.
  10. Lanier LL. Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol. 2008 May; 9(5):495-502.
  11. Satoh T, Arii J, Suenaga T, Wang J, Kogure A, Uehori J, Arase N, Shiratori I, Tanaka S, Kawaguchi Y, Spear PG, Lanier LL, Arase H. PILRalpha is a herpes simplex virus-1 entry coreceptor that associates with glycoprotein B. Cell. 2008 Mar 21; 132(6):935-44.
  12. Lanier LL. Evolutionary struggles between NK cells and viruses. Nat Rev Immunol. 2008 Apr; 8(4):259-68.
  13. Long BR, Ndhlovu LC, Oksenberg JR, Lanier LL, Hecht FM, Nixon DF, Barbour JD. Conferral of enhanced natural killer cell function by KIR3DS1 in early human immunodeficiency virus type 1 infection. J Virol. 2008 May; 82(10):4785-92.
  14. Fang M, Lanier LL, Sigal LJ. A role for NKG2D in NK cell-mediated resistance to poxvirus disease. PLoS Pathog. 2008 Feb 08; 4(2):e30.
  15. Wang J, Shiratori I, Satoh T, Lanier LL, Arase H. An essential role of sialylated O-linked sugar chains in the recognition of mouse CD99 by paired Ig-like type 2 receptor (PILR). J Immunol. 2008 Feb 01; 180(3):1686-93.
  16. Michaëlsson J, Long BR, Loo CP, Lanier LL, Spotts G, Hecht FM, Nixon DF. Immune reconstitution of CD56(dim) NK cells in individuals with primary HIV-1 infection treated with interleukin-2. J Infect Dis. 2008 Jan 01; 197(1):117-25.
  17. Chu CL, Yu YL, Shen KY, Lowell CA, Lanier LL, Hamerman JA. Increased TLR responses in dendritic cells lacking the ITAM-containing adapters DAP12 and FcRgamma. Eur J Immunol. 2008 Jan; 38(1):166-73.
  18. Walsh KB, Lanier LL, Lane TE. NKG2D receptor signaling enhances cytolytic activity by virus-specific CD8+ T cells: evidence for a protective role in virus-induced encephalitis. J Virol. 2008 Mar; 82(6):3031-44.
  19. Walsh KB, Lodoen MB, Edwards RA, Lanier LL, Lane TE. Evidence for differential roles for NKG2D receptor signaling in innate host defense against coronavirus-induced neurological and liver disease. J Virol. 2008 Mar; 82(6):3021-30.
  20. Kim J, Chang CK, Hayden T, Liu FC, Benjamin J, Hamerman JA, Lanier LL, Kang SM. The activating immunoreceptor NKG2D and its ligands are involved in allograft transplant rejection. J Immunol. 2007 Nov 15; 179(10):6416-20.
  21. Long BR, Michaelsson J, Loo CP, Ballan WM, Vu BA, Hecht FM, Lanier LL, Chapman JM, Nixon DF. Elevated frequency of gamma interferon-producing NK cells in healthy adults vaccinated against influenza virus. Clin Vaccine Immunol. 2008 Jan; 15(1):120-30.
  22. Vilarinho S, Ogasawara K, Nishimura S, Lanier LL, Baron JL. Blockade of NKG2D on NKT cells prevents hepatitis and the acute immune response to hepatitis B virus. Proc Natl Acad Sci U S A. 2007 Nov 13; 104(46):18187-92.
  23. Cao W, Zhang L, Rosen DB, Bover L, Watanabe G, Bao M, Lanier LL, Liu YJ. BDCA2/Fc epsilon RI gamma complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells. PLoS Biol. 2007 Sep 11; 5(10):e248.
  24. Ballan WM, Vu BA, Long BR, Loo CP, Michaëlsson J, Barbour JD, Lanier LL, Wiznia AA, Abadi J, Fennelly GJ, Rosenberg MG, Nixon DF. Natural killer cells in perinatally HIV-1-infected children exhibit less degranulation compared to HIV-1-exposed uninfected children and their expression of KIR2DL3, NKG2C, and NKp46 correlates with disease severity. J Immunol. 2007 Sep 01; 179(5):3362-70.
  25. Wu Y, Torchia J, Yao W, Lane NE, Lanier LL, Nakamura MC, Humphrey MB. Bone microenvironment specific roles of ITAM adapter signaling during bone remodeling induced by acute estrogen-deficiency. PLoS One. 2007 Jul 04; 2(7):e586.