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. Arase H, Saito T, Phillips JH, Lanier LL. Cutting edge: the mouse NK cell-associated antigen recognized by DX5 monoclonal antibody is CD49b (alpha 2 integrin, very late antigen-2). J Immunol. 2001 Aug 01; 167(3):1141-4.
  2. O'Callaghan CA, Cerwenka A, Willcox BE, Lanier LL, Bjorkman PJ. Molecular competition for NKG2D: H60 and RAE1 compete unequally for NKG2D with dominance of H60. Immunity. 2001 Aug; 15(2):201-11.
  3. André P, Biassoni R, Colonna M, Cosman D, Lanier LL, Long EO, Lopez-Botet M, Moretta A, Moretta L, Parham P, Trowsdale J, Vivier E, Wagtmann N, Wilson MJ. New nomenclature for MHC receptors. Nat Immunol. 2001 Aug; 2(8):661.
  4. Meyaard L, van der Vuurst de Vries AR, de Ruiter T, Lanier LL, Phillips JH, Clevers H. The epithelial cellular adhesion molecule (Ep-CAM) is a ligand for the leukocyte-associated immunoglobulin-like receptor (LAIR). J Exp Med. 2001 Jul 02; 194(1):107-12.
  5. Lanier LL. Face off--the interplay between activating and inhibitory immune receptors. Curr Opin Immunol. 2001 Jun; 13(3):326-31.
  6. Cerwenka A, Lanier LL. Ligands for natural killer cell receptors: redundancy or specificity. Immunol Rev. 2001 Jun; 181:158-69.
  7. Kadowaki N, Antonenko S, Ho S, Rissoan MC, Soumelis V, Porcelli SA, Lanier LL, Liu YJ. Distinct cytokine profiles of neonatal natural killer T cells after expansion with subsets of dendritic cells. J Exp Med. 2001 May 21; 193(10):1221-6.
  8. Steinle A, Li P, Morris DL, Groh V, Lanier LL, Strong RK, Spies T. Interactions of human NKG2D with its ligands MICA, MICB, and homologs of the mouse RAE-1 protein family. Immunogenetics. 2001 May-Jun; 53(4):279-87.
  9. Yim D, Jie HB, Sotiriadis J, Kim YS, Kim KS, Rothschild MF, Lanier LL, Kim YB. Molecular cloning and characterization of pig immunoreceptor DAP10 and NKG2D. Immunogenetics. 2001 Apr; 53(3):243-9.
  10. Young NT, Uhrberg M, Phillips JH, Lanier LL, Parham P. Differential expression of leukocyte receptor complex-encoded Ig-like receptors correlates with the transition from effector to memory CTL. J Immunol. 2001 Mar 15; 166(6):3933-41.
  11. Uhrberg M, Valiante NM, Young NT, Lanier LL, Phillips JH, Parham P. The repertoire of killer cell Ig-like receptor and CD94:NKG2A receptors in T cells: clones sharing identical alpha beta TCR rearrangement express highly diverse killer cell Ig-like receptor patterns. J Immunol. 2001 Mar 15; 166(6):3923-32.
  12. Daws MR, Lanier LL, Seaman WE, Ryan JC. Cloning and characterization of a novel mouse myeloid DAP12-associated receptor family. Eur J Immunol. 2001 Mar; 31(3):783-91.
  13. Lanier LL. On guard--activating NK cell receptors. Nat Immunol. 2001 Jan; 2(1):23-7.
  14. Lanier LL, Bakker AB. The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function. Immunol Today. 2000 Dec; 21(12):611-4.
  15. Shibuya A, Sakamoto N, Shimizu Y, Shibuya K, Osawa M, Hiroyama T, Eyre HJ, Sutherland GR, Endo Y, Fujita T, Miyabayashi T, Sakano S, Tsuji T, Nakayama E, Phillips JH, Lanier LL, Nakauchi H. Fc alpha/mu receptor mediates endocytosis of IgM-coated microbes. Nat Immunol. 2000 Nov; 1(5):441-6.
  16. Ravetch JV, Lanier LL. Immune inhibitory receptors. Science. 2000 Oct 06; 290(5489):84-9.
  17. Wu J, Cherwinski H, Spies T, Phillips JH, Lanier LL. DAP10 and DAP12 form distinct, but functionally cooperative, receptor complexes in natural killer cells. J Exp Med. 2000 Oct 02; 192(7):1059-68.
  18. Tangye SG, Phillips JH, Lanier LL, Nichols KE. Functional requirement for SAP in 2B4-mediated activation of human natural killer cells as revealed by the X-linked lymphoproliferative syndrome. J Immunol. 2000 Sep 15; 165(6):2932-6.
  19. Bakker AB, Hoek RM, Cerwenka A, Blom B, Lucian L, McNeil T, Murray R, Phillips LH, Sedgwick JD, Lanier LL. DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming. Immunity. 2000 Sep; 13(3):345-53.
  20. Muench MO, Humeau L, Paek B, Ohkubo T, Lanier LL, Albanese CT, Bárcena A. Differential effects of interleukin-3, interleukin-7, interleukin 15, and granulocyte-macrophage colony-stimulating factor in the generation of natural killer and B cells from primitive human fetal liver progenitors. Exp Hematol. 2000 Aug; 28(8):961-73.
  21. Paloneva J, Kestilä M, Wu J, Salminen A, Böhling T, Ruotsalainen V, Hakola P, Bakker AB, Phillips JH, Pekkarinen P, Lanier LL, Timonen T, Peltonen L. Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts. Nat Genet. 2000 Jul; 25(3):357-61.
  22. Tangye SG, Cherwinski H, Lanier LL, Phillips JH. 2B4-mediated activation of human natural killer cells. Mol Immunol. 2000 Jun; 37(9):493-501.
  23. Khakoo SI, Rajalingam R, Shum BP, Weidenbach K, Flodin L, Muir DG, Canavez F, Cooper SL, Valiante NM, Lanier LL, Parham P. Rapid evolution of NK cell receptor systems demonstrated by comparison of chimpanzees and humans. Immunity. 2000 Jun; 12(6):687-98.
  24. Cerwenka A, Bakker AB, McClanahan T, Wagner J, Wu J, Phillips JH, Lanier LL. Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice. Immunity. 2000 Jun; 12(6):721-7.
  25. Yim D, Jie HB, Lanier LL, Kim YB. Molecular cloning, gene structure, and expression pattern of pig immunoreceptor DAP12. Immunogenetics. 2000 May; 51(6):436-42.