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. Cayabyab M, Phillips JH, Lanier LL. CD40 preferentially costimulates activation of CD4+ T lymphocytes. J Immunol. 1994 Feb 15; 152(4):1523-31.
  2. Sánchez MJ, Spits H, Lanier LL, Phillips JH. Human natural killer cell committed thymocytes and their relation to the T cell lineage. J Exp Med. 1993 Dec 01; 178(6):1857-66.
  3. Azuma M, Ito D, Yagita H, Okumura K, Phillips JH, Lanier LL, Somoza C. B70 antigen is a second ligand for CTLA-4 and CD28. Nature. 1993 Nov 04; 366(6450):76-9.
  4. Litwin V, Gumperz J, Parham P, Phillips JH, Lanier LL. Specificity of HLA class I antigen recognition by human NK clones: evidence for clonal heterogeneity, protection by self and non-self alleles, and influence of the target cell type. J Exp Med. 1993 Oct 01; 178(4):1321-36.
  5. Yssel H, Schneider PV, Lanier LL. Interleukin-7 specifically induces the B7/BB1 antigen on human cord blood and peripheral blood T cells and T cell clones. Int Immunol. 1993 Jul; 5(7):753-9.
  6. Lanier LL. Distribution and function of lymphocyte surface antigens. Molecules costimulating T lymphocyte activation and effector function. Ann N Y Acad Sci. 1993 Mar 20; 677:86-93.
  7. Azuma M, Cayabyab M, Phillips JH, Lanier LL. Requirements for CD28-dependent T cell-mediated cytotoxicity. J Immunol. 1993 Mar 15; 150(6):2091-101.
  8. Azuma M, Yssel H, Phillips JH, Spits H, Lanier LL. Functional expression of B7/BB1 on activated T lymphocytes. J Exp Med. 1993 Mar 01; 177(3):845-50.
  9. Azuma M, Phillips JH, Lanier LL. CD28- T lymphocytes. Antigenic and functional properties. J Immunol. 1993 Feb 15; 150(4):1147-59.
  10. Lanier LL, Spits H, Phillips JH. The developmental relationship between NK cells and T cells. Immunol Today. 1992 Oct; 13(10):392-5.
  11. Lanier LL, Chang C, Spits H, Phillips JH. Expression of cytoplasmic CD3 epsilon proteins in activated human adult natural killer (NK) cells and CD3 gamma, delta, epsilon complexes in fetal NK cells. Implications for the relationship of NK and T lymphocytes. J Immunol. 1992 Sep 15; 149(6):1876-80.
  12. Hori T, Phillips JH, Duncan B, Lanier LL, Spits H. Human fetal liver-derived CD7+CD2lowCD3-CD56- clones that express CD3 gamma, delta, and epsilon and proliferate in response to interleukin-2 (IL-2), IL-3, IL-4, or IL-7: implications for the relationship between T and natural killer cells. Blood. 1992 Sep 01; 80(5):1270-8.
  13. Azuma M, Cayabyab M, Buck D, Phillips JH, Lanier LL. Involvement of CD28 in MHC-unrestricted cytotoxicity mediated by a human natural killer leukemia cell line. J Immunol. 1992 Aug 15; 149(4):1115-23.
  14. Phillips JH, Hori T, Nagler A, Bhat N, Spits H, Lanier LL. Ontogeny of human natural killer (NK) cells: fetal NK cells mediate cytolytic function and express cytoplasmic CD3 epsilon,delta proteins. J Exp Med. 1992 Apr 01; 175(4):1055-66.
  15. Azuma M, Cayabyab M, Buck D, Phillips JH, Lanier LL. CD28 interaction with B7 costimulates primary allogeneic proliferative responses and cytotoxicity mediated by small, resting T lymphocytes. J Exp Med. 1992 Feb 01; 175(2):353-60.
  16. Lanier LL, Phillips JH. Natural killer cells. Curr Opin Immunol. 1992 Feb; 4(1):38-42.
  17. Azuma M, Phillips JH, Lanier LL. CD28 co-stimulation of T-cell-mediated cytotoxicity. Int J Cancer Suppl. 1992; 7:33-5.
  18. Phillips JH, McKinney L, Azuma M, Spits H, Lanier LL. A novel beta 4, alpha 6 integrin-associated epithelial cell antigen involved in natural killer cell and antigen-specific cytotoxic T lymphocyte cytotoxicity. J Exp Med. 1991 Dec 01; 174(6):1571-81.
  19. Harrison D, Phillips JH, Lanier LL. Involvement of a metalloprotease in spontaneous and phorbol ester-induced release of natural killer cell-associated Fc gamma RIII (CD16-II). J Immunol. 1991 Nov 15; 147(10):3459-65.
  20. Lanier LL, Chang C, Azuma M, Ruitenberg JJ, Hemperly JJ, Phillips JH. Molecular and functional analysis of human natural killer cell-associated neural cell adhesion molecule (N-CAM/CD56). J Immunol. 1991 Jun 15; 146(12):4421-6.
  21. Templeton DJ, Park SH, Lanier L, Weinberg RA. Nonfunctional mutants of the retinoblastoma protein are characterized by defects in phosphorylation, viral oncoprotein association, and nuclear tethering. Proc Natl Acad Sci U S A. 1991 Apr 15; 88(8):3033-7.
  22. Phillips JH, Chang CW, Lanier LL. Platelet-induced expression of Fc gamma RIII (CD16) on human monocytes. Eur J Immunol. 1991 Apr; 21(4):895-9.
  23. Lanier LL, Yu G, Phillips JH. Analysis of Fc gamma RIII (CD16) membrane expression and association with CD3 zeta and Fc epsilon RI-gamma by site-directed mutation. J Immunol. 1991 Mar 01; 146(5):1571-6.
  24. Nagler A, Lanier LL, Phillips JH. Constitutive expression of high affinity interleukin 2 receptors on human CD16-natural killer cells in vivo. J Exp Med. 1990 May 01; 171(5):1527-33.
  25. Lanier LL, Cwirla S, Yu G, Testi R, Phillips JH. Membrane anchoring of a human IgG Fc receptor (CD16) determined by a single amino acid. Science. 1989 Dec 22; 246(4937):1611-3.