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. Turning on natural killer cells. J Exp Med. 2000 Apr 17; 191(8):1259-62.
  2. Tangye SG, Phillips JH, Lanier LL. The CD2-subset of the Ig superfamily of cell surface molecules: receptor-ligand pairs expressed by NK cells and other immune cells. Semin Immunol. 2000 Apr; 12(2):149-57.
  3. Lanier LL. The origin and functions of natural killer cells. Clin Immunol. 2000 Apr; 95(1 Pt 2):S14-8.
  4. Pauza M, Smith KM, Neal H, Reilly C, Lanier LL, Lo D. Transgenic expression of Ly-49A in thymocytes alters repertoire selection. J Immunol. 2000 Jan 15; 164(2):884-92.
  5. Bakker AB, Wu J, Phillips JH, Lanier LL. NK cell activation: distinct stimulatory pathways counterbalancing inhibitory signals. Hum Immunol. 2000 Jan; 61(1):18-27.
  6. Chang C, Lanier LL. Use of cDNA library expression cloning to identify components of heterodimeric receptor complexes. Methods Mol Biol. 2000; 121:273-81.
  7. Castro AG, Hauser TM, Cocks BG, Abrams J, Zurawski S, Churakova T, Zonin F, Robinson D, Tangye SG, Aversa G, Nichols KE, de Vries JE, Lanier LL, O'Garra A. Molecular and functional characterization of mouse signaling lymphocytic activation molecule (SLAM): differential expression and responsiveness in Th1 and Th2 cells. J Immunol. 1999 Dec 01; 163(11):5860-70.
  8. Shibuya K, Lanier LL, Phillips JH, Ochs HD, Shimizu K, Nakayama E, Nakauchi H, Shibuya A. Physical and functional association of LFA-1 with DNAM-1 adhesion molecule. Immunity. 1999 Nov; 11(5):615-23.
  9. Bakker AB, Baker E, Sutherland GR, Phillips JH, Lanier LL. Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells. Proc Natl Acad Sci U S A. 1999 Aug 17; 96(17):9792-6.
  10. Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 1999 Jul 30; 285(5428):727-9.
  11. Wu J, Song Y, Bakker AB, Bauer S, Spies T, Lanier LL, Phillips JH. An activating immunoreceptor complex formed by NKG2D and DAP10. Science. 1999 Jul 30; 285(5428):730-2.
  12. Tangye SG, Lazetic S, Woollatt E, Sutherland GR, Lanier LL, Phillips JH. Cutting edge: human 2B4, an activating NK cell receptor, recruits the protein tyrosine phosphatase SHP-2 and the adaptor signaling protein SAP. J Immunol. 1999 Jun 15; 162(12):6981-5.
  13. Meyaard L, Hurenkamp J, Clevers H, Lanier LL, Phillips JH. Leukocyte-associated Ig-like receptor-1 functions as an inhibitory receptor on cytotoxic T cells. J Immunol. 1999 May 15; 162(10):5800-4.
  14. Lanier LL. Natural killer cells fertile with receptors for HLA-G? Proc Natl Acad Sci U S A. 1999 May 11; 96(10):5343-5.
  15. Allan DS, Colonna M, Lanier LL, Churakova TD, Abrams JS, Ellis SA, McMichael AJ, Braud VM. Tetrameric complexes of human histocompatibility leukocyte antigen (HLA)-G bind to peripheral blood myelomonocytic cells. J Exp Med. 1999 Apr 05; 189(7):1149-56.
  16. Tangye SG, Wu J, Aversa G, de Vries JE, Lanier LL, Phillips JH. Negative regulation of human T cell activation by the receptor-type protein tyrosine phosphatase CD148. J Immunol. 1998 Oct 15; 161(8):3803-7.
  17. Tangye SG, Phillips JH, Lanier LL, de Vries JE, Aversa G. CD148: a receptor-type protein tyrosine phosphatase involved in the regulation of human T cell activation. J Immunol. 1998 Oct 01; 161(7):3249-55.
  18. Barton K, Muthusamy N, Fischer C, Ting CN, Walunas TL, Lanier LL, Leiden JM. The Ets-1 transcription factor is required for the development of natural killer cells in mice. Immunity. 1998 Oct; 9(4):555-63.
  19. Shibuya A, Lanier LL, Phillips JH. Protein kinase C is involved in the regulation of both signaling and adhesion mediated by DNAX accessory molecule-1 receptor. J Immunol. 1998 Aug 15; 161(4):1671-6.
  20. Smith KM, Wu J, Bakker AB, Phillips JH, Lanier LL. Ly-49D and Ly-49H associate with mouse DAP12 and form activating receptors. J Immunol. 1998 Jul 01; 161(1):7-10.
  21. Lanier LL, Corliss B, Wu J, Phillips JH. Association of DAP12 with activating CD94/NKG2C NK cell receptors. Immunity. 1998 Jun; 8(6):693-701.
  22. Bakker AB, Phillips JH, Figdor CG, Lanier LL. Killer cell inhibitory receptors for MHC class I molecules regulate lysis of melanoma cells mediated by NK cells, gamma delta T cells, and antigen-specific CTL. J Immunol. 1998 Jun 01; 160(11):5239-45.
  23. Leong CC, Chapman TL, Bjorkman PJ, Formankova D, Mocarski ES, Phillips JH, Lanier LL. Modulation of natural killer cell cytotoxicity in human cytomegalovirus infection: the role of endogenous class I major histocompatibility complex and a viral class I homolog. J Exp Med. 1998 May 18; 187(10):1681-7.
  24. Lanier LL. Follow the leader: NK cell receptors for classical and nonclassical MHC class I. Cell. 1998 Mar 20; 92(6):705-7.
  25. Braud VM, Allan DS, O'Callaghan CA, Söderström K, D'Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature. 1998 Feb 19; 391(6669):795-9.