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. Barber LD, Patel TP, Percival L, Gumperz JE, Lanier LL, Phillips JH, Bigge JC, Wormwald MR, Parekh RB, Parham P. Unusual uniformity of the N-linked oligosaccharides of HLA-A, -B, and -C glycoproteins. J Immunol. 1996 May 01; 156(9):3275-84.
  2. Gumperz JE, Valiante NM, Parham P, Lanier LL, Tyan D. Heterogeneous phenotypes of expression of the NKB1 natural killer cell class I receptor among individuals of different human histocompatibility leukocyte antigens types appear genetically regulated, but not linked to major histocompatibililty complex haplotype. J Exp Med. 1996 Apr 01; 183(4):1817-27.
  3. Onishi M, Kinoshita S, Morikawa Y, Shibuya A, Phillips J, Lanier LL, Gorman DM, Nolan GP, Miyajima A, Kitamura T. Applications of retrovirus-mediated expression cloning. Exp Hematol. 1996 Feb; 24(2):324-9.
  4. Long EO, Colonna M, Lanier LL. Inhibitory MHC class I receptors on NK and T cells: a standard nomenclature. Immunol Today. 1996 Feb; 17(2):100.
  5. Lanier LL, Phillips JH. Inhibitory MHC class I receptors on NK cells and T cells. Immunol Today. 1996 Feb; 17(2):86-91.
  6. D'Andrea A, Lanier LL. NKB1: a killer cell inhibitory receptor for class I HLA-B allotypes. Chem Immunol. 1996; 64:104-15.
  7. Lanier LL. The role of natural killer cells in transplantation. Curr Opin Immunol. 1995 Oct; 7(5):626-31.
  8. Chang C, Rodríguez A, Carretero M, López-Botet M, Phillips JH, Lanier LL. Molecular characterization of human CD94: a type II membrane glycoprotein related to the C-type lectin superfamily. Eur J Immunol. 1995 Sep; 25(9):2433-7.
  9. D'Andrea A, Chang C, Franz-Bacon K, McClanahan T, Phillips JH, Lanier LL. Molecular cloning of NKB1. A natural killer cell receptor for HLA-B allotypes. J Immunol. 1995 Sep 01; 155(5):2306-10.
  10. Spits H, Lanier LL, Phillips JH. Development of human T and natural killer cells. Blood. 1995 May 15; 85(10):2654-70.
  11. Warren HS, Kinnear BF, Phillips JH, Lanier LL. Production of IL-5 by human NK cells and regulation of IL-5 secretion by IL-4, IL-10, and IL-12. J Immunol. 1995 May 15; 154(10):5144-52.
  12. Fernández-Ruiz E, Somoza C, Sánchez-Madrid F, Lanier LL. CD28/CTLA-4 ligands: the gene encoding CD86 (B70/B7.2) maps to the same region as CD80 (B7/B7.1) gene in human chromosome 3q13-q23. Eur J Immunol. 1995 May; 25(5):1453-6.
  13. Phillips JH, Gumperz JE, Parham P, Lanier LL. Superantigen-dependent, cell-mediated cytotoxicity inhibited by MHC class I receptors on T lymphocytes. Science. 1995 Apr 21; 268(5209):403-5.
  14. Lanier LL, Phillips JH. NK cell recognition of major histocompatibility complex class I molecules. Semin Immunol. 1995 Apr; 7(2):75-82.
  15. Lanier LL, Gumperz JE, Parham P, Melero I, López-Botet M, Phillips JH. The NKB1 and HP-3E4 NK cells receptors are structurally distinct glycoproteins and independently recognize polymorphic HLA-B and HLA-C molecules. J Immunol. 1995 Apr 01; 154(7):3320-7.
  16. Somoza C, Lanier LL. T-cell costimulation via CD28-CD80/CD86 and CD40-CD40 ligand interactions. Res Immunol. 1995 Mar-Apr; 146(3):171-6.
  17. Gumperz JE, Litwin V, Phillips JH, Lanier LL, Parham P. The Bw4 public epitope of HLA-B molecules confers reactivity with natural killer cell clones that express NKB1, a putative HLA receptor. J Exp Med. 1995 Mar 01; 181(3):1133-44.
  18. Lanier LL, O'Fallon S, Somoza C, Phillips JH, Linsley PS, Okumura K, Ito D, Azuma M. CD80 (B7) and CD86 (B70) provide similar costimulatory signals for T cell proliferation, cytokine production, and generation of CTL. J Immunol. 1995 Jan 01; 154(1):97-105.
  19. Azuma M, Lanier LL. The role of CD28 costimulation in the generation of cytotoxic T lymphocytes. Curr Top Microbiol Immunol. 1995; 198:59-74.
  20. Caux C, Vanbervliet B, Massacrier C, Azuma M, Okumura K, Lanier LL, Banchereau J. B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J Exp Med. 1994 Nov 01; 180(5):1841-7.
  21. Cifone MG, De Maria R, Roncaioli P, Rippo MR, Azuma M, Lanier LL, Santoni A, Testi R. Apoptotic signaling through CD95 (Fas/Apo-1) activates an acidic sphingomyelinase. J Exp Med. 1994 Oct 01; 180(4):1547-52.
  22. Lanier LL, Chang C, Phillips JH. Human NKR-P1A. A disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes. J Immunol. 1994 Sep 15; 153(6):2417-28.
  23. Sánchez MJ, Muench MO, Roncarolo MG, Lanier LL, Phillips JH. Identification of a common T/natural killer cell progenitor in human fetal thymus. J Exp Med. 1994 Aug 01; 180(2):569-76.
  24. Litwin V, Gumperz J, Parham P, Phillips JH, Lanier LL. NKB1: a natural killer cell receptor involved in the recognition of polymorphic HLA-B molecules. J Exp Med. 1994 Aug 01; 180(2):537-43.
  25. Murphy EE, Terres G, Macatonia SE, Hsieh CS, Mattson J, Lanier L, Wysocka M, Trinchieri G, Murphy K, O'Garra A. B7 and interleukin 12 cooperate for proliferation and interferon gamma production by mouse T helper clones that are unresponsive to B7 costimulation. J Exp Med. 1994 Jul 01; 180(1):223-31.