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. Lanier LL, Corliss BC, Wu J, Leong C, Phillips JH. Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells. Nature. 1998 Feb 12; 391(6668):703-7.
  2. Lanier LL. Activating and inhibitory NK cell receptors. Adv Exp Med Biol. 1998; 452:13-8.
  3. D'Andrea A, Lanier LL. Killer cell inhibitory receptor expression by T cells. Curr Top Microbiol Immunol. 1998; 230:25-39.
  4. Lanier LL. NK cell receptors. Annu Rev Immunol. 1998; 16:359-93.
  5. Valiante NM, Uhrberg M, Shilling HG, Lienert-Weidenbach K, Arnett KL, D'Andrea A, Phillips JH, Lanier LL, Parham P. Functionally and structurally distinct NK cell receptor repertoires in the peripheral blood of two human donors. Immunity. 1997 Dec; 7(6):739-51.
  6. Uhrberg M, Valiante NM, Shum BP, Shilling HG, Lienert-Weidenbach K, Corliss B, Tyan D, Lanier LL, Parham P. Human diversity in killer cell inhibitory receptor genes. Immunity. 1997 Dec; 7(6):753-63.
  7. Söderström K, Corliss B, Lanier LL, Phillips JH. CD94/NKG2 is the predominant inhibitory receptor involved in recognition of HLA-G by decidual and peripheral blood NK cells. J Immunol. 1997 Aug 01; 159(3):1072-5.
  8. Meyaard L, Adema GJ, Chang C, Woollatt E, Sutherland GR, Lanier LL, Phillips JH. LAIR-1, a novel inhibitory receptor expressed on human mononuclear leukocytes. Immunity. 1997 Aug; 7(2):283-90.
  9. Jaleco AC, Blom B, Res P, Weijer K, Lanier LL, Phillips JH, Spits H. Fetal liver contains committed NK progenitors, but is not a site for development of CD34+ cells into T cells. J Immunol. 1997 Jul 15; 159(2):694-702.
  10. Gumperz JE, Barber LD, Valiante NM, Percival L, Phillips JH, Lanier LL, Parham P. Conserved and variable residues within the Bw4 motif of HLA-B make separable contributions to recognition by the NKB1 killer cell-inhibitory receptor. J Immunol. 1997 Jun 01; 158(11):5237-41.
  11. Houchins JP, Lanier LL, Niemi EC, Phillips JH, Ryan JC. Natural killer cell cytolytic activity is inhibited by NKG2-A and activated by NKG2-C. J Immunol. 1997 Apr 15; 158(8):3603-9.
  12. Lanier LL. Natural killer cells: from no receptors to too many. Immunity. 1997 Apr; 6(4):371-8.
  13. Lanier LL, Corliss B, Phillips JH. Arousal and inhibition of human NK cells. Immunol Rev. 1997 Feb; 155:145-54.
  14. Lanier LL. Natural killer cell receptors and MHC class I interactions. Curr Opin Immunol. 1997 Feb; 9(1):126-31.
  15. Renedo M, Arce I, Rodríguez A, Carretero M, Lanier LL, López-Botet M, Fernández-Ruiz E. The human natural killer gene complex is located on chromosome 12p12-p13. Immunogenetics. 1997; 46(4):307-11.
  16. Lazetic S, Chang C, Houchins JP, Lanier LL, Phillips JH. Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits. J Immunol. 1996 Dec 01; 157(11):4741-5.
  17. Valiante NM, Phillips JH, Lanier LL, Parham P. Killer cell inhibitory receptor recognition of human leukocyte antigen (HLA) class I blocks formation of a pp36/PLC-gamma signaling complex in human natural killer (NK) cells. J Exp Med. 1996 Dec 01; 184(6):2243-50.
  18. Binstadt BA, Brumbaugh KM, Dick CJ, Scharenberg AM, Williams BL, Colonna M, Lanier LL, Kinet JP, Abraham RT, Leibson PJ. Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK cells inhibits FcR-initiated tyrosine kinase activation. Immunity. 1996 Dec; 5(6):629-38.
  19. Gumperz JE, Paterson JC, Litwin V, Valiante N, Lanier LL, Parham P, Little AM. Specificity of two anti-class I HLA monoclonal antibodies that block class I recognition by the NKB1 killer cell inhibitory receptor. Tissue Antigens. 1996 Oct; 48(4 Pt 1):278-84.
  20. Phillips JH, Chang C, Mattson J, Gumperz JE, Parham P, Lanier LL. CD94 and a novel associated protein (94AP) form a NK cell receptor involved in the recognition of HLA-A, HLA-B, and HLA-C allotypes. Immunity. 1996 Aug; 5(2):163-72.
  21. D'Andrea A, Chang C, Phillips JH, Lanier LL. Regulation of T cell lymphokine production by killer cell inhibitory receptor recognition of self HLA class I alleles. J Exp Med. 1996 Aug 01; 184(2):789-94.
  22. Barber LD, Percival L, Valiante NM, Chen L, Lee C, Gumperz JE, Phillips JH, Lanier LL, Bigge JC, Parekh RB, Parham P. The inter-locus recombinant HLA-B*4601 has high selectivity in peptide binding and functions characteristic of HLA-C. J Exp Med. 1996 Aug 01; 184(2):735-40.
  23. Fry AM, Lanier LL, Weiss A. Phosphotyrosines in the killer cell inhibitory receptor motif of NKB1 are required for negative signaling and for association with protein tyrosine phosphatase 1C. J Exp Med. 1996 Jul 01; 184(1):295-300.
  24. Shibuya A, Campbell D, Hannum C, Yssel H, Franz-Bacon K, McClanahan T, Kitamura T, Nicholl J, Sutherland GR, Lanier LL, Phillips JH. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity. 1996 Jun; 4(6):573-81.
  25. Warren HS, Kinnear BF, Kastelein RL, Lanier LL. Analysis of the costimulatory role of IL-2 and IL-15 in initiating proliferation of resting (CD56dim) human NK cells. J Immunol. 1996 May 01; 156(9):3254-9.