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, Yu G, Phillips JH. Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells. Nature. 1989 Dec 14; 342(6251):803-5.
  2. Nagler A, Lanier LL, Cwirla S, Phillips JH. Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol. 1989 Nov 15; 143(10):3183-91.
  3. Testi R, Phillips JH, Lanier LL. T cell activation via Leu-23 (CD69). J Immunol. 1989 Aug 15; 143(4):1123-8.
  4. Phillips JH, Takeshita T, Sugamura K, Lanier LL. Activation of natural killer cells via the p75 interleukin 2 receptor. J Exp Med. 1989 Jul 01; 170(1):291-6.
  5. Clark EA, Lanier LL. Report from Vienna: in search of all surface molecules expressed on human leukocytes. J Clin Immunol. 1989 Jul; 9(4):265-72.
  6. Lanier LL, Testi R, Bindl J, Phillips JH. Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med. 1989 Jun 01; 169(6):2233-8.
  7. Groh V, Porcelli S, Fabbi M, Lanier LL, Picker LJ, Anderson T, Warnke RA, Bhan AK, Strominger JL, Brenner MB. Human lymphocytes bearing T cell receptor gamma/delta are phenotypically diverse and evenly distributed throughout the lymphoid system. J Exp Med. 1989 Apr 01; 169(4):1277-94.
  8. Lanier LL, Phillips JH, Testi R. Membrane anchoring and spontaneous release of CD16 (FcR III) by natural killer cells and granulocytes. Eur J Immunol. 1989 Apr; 19(4):775-8.
  9. Testi R, Phillips JH, Lanier LL. Leu 23 induction as an early marker of functional CD3/T cell antigen receptor triggering. Requirement for receptor cross-linking, prolonged elevation of intracellular [Ca++] and stimulation of protein kinase C. J Immunol. 1989 Mar 15; 142(6):1854-60.
  10. Loh EY, Elliott JF, Cwirla S, Lanier LL, Davis MM. Polymerase chain reaction with single-sided specificity: analysis of T cell receptor delta chain. Science. 1989 Jan 13; 243(4888):217-20.
  11. Testi R, Lanier LL. Functional expression of CD28 on T cell antigen receptor gamma/delta-bearing T lymphocytes. Eur J Immunol. 1989 Jan; 19(1):185-8.
  12. Loh EY, Cwirla S, Serafini AT, Phillips JH, Lanier LL. Human T-cell-receptor delta chain: genomic organization, diversity, and expression in populations of cells. Proc Natl Acad Sci U S A. 1988 Dec; 85(24):9714-8.
  13. Lanier LL, Ruitenberg J, Bolhuis RL, Borst J, Phillips JH, Testi R. Structural and serological heterogeneity of gamma/delta T cell antigen receptor expression in thymus and peripheral blood. Eur J Immunol. 1988 Dec; 18(12):1985-92.
  14. Lanier LL, Ruitenberg JJ, Phillips JH. Functional and biochemical analysis of CD16 antigen on natural killer cells and granulocytes. J Immunol. 1988 Nov 15; 141(10):3478-85.
  15. Arnaout MA, Lanier LL, Faller DV. Relative contribution of the leukocyte molecules Mo1, LFA-1, and p150,95 (LeuM5) in adhesion of granulocytes and monocytes to vascular endothelium is tissue- and stimulus-specific. J Cell Physiol. 1988 Nov; 137(2):305-9.
  16. Testi R, Phillips JH, Lanier LL. Constitutive expression of a phosphorylated activation antigen (Leu 23) by CD3bright human thymocytes. J Immunol. 1988 Oct 15; 141(8):2557-63.
  17. Nagler A, Lanier LL, Phillips JH. The effects of IL-4 on human natural killer cells. A potent regulator of IL-2 activation and proliferation. J Immunol. 1988 Oct 01; 141(7):2349-51.
  18. Lanier LL, Phillips JH. Effectors, repertoire and receptors involved in lymphocyte-mediated mhc-unrestricted cytotoxicity. Ann Inst Pasteur Immunol. 1988 Jul-Aug; 139(4):450-6.
  19. Nagler A, Greenberg PL, Lanier LL, Phillips JH. The effects of recombinant interleukin 2-activated natural killer cells on autologous peripheral blood hematopoietic progenitors. J Exp Med. 1988 Jul 01; 168(1):47-54.
  20. Lanier LL, Buck DW, Rhodes L, Ding A, Evans E, Barney C, Phillips JH. Interleukin 2 activation of natural killer cells rapidly induces the expression and phosphorylation of the Leu-23 activation antigen. J Exp Med. 1988 May 01; 167(5):1572-85.
  21. Skettino S, Phillips J, Lanier L, Nagler A, Greenberg P. Selective generation of erythroid burst-promoting activity by recombinant interleukin 2-stimulated human T lymphocytes and natural killer cells. Blood. 1988 Apr; 71(4):907-14.
  22. Richie ER, McEntire B, Crispe N, Kimura J, Lanier LL, Allison JP. Alpha/beta T-cell antigen receptor gene and protein expression occurs at early stages of thymocyte differentiation. Proc Natl Acad Sci U S A. 1988 Feb; 85(4):1174-8.
  23. Loh EY, Lanier LL, Turck CW, Littman DR, Davis MM, Chien YH, Weiss A. Identification and sequence of a fourth human T cell antigen receptor chain. Nature. 1987 Dec 10-16; 330(6148):569-72.
  24. Phillips JH, Gemlo BT, Myers WW, Rayner AA, Lanier LL. In vivo and in vitro activation of natural killer cells in advanced cancer patients undergoing combined recombinant interleukin-2 and LAK cell therapy. J Clin Oncol. 1987 Dec; 5(12):1933-41.
  25. Weiss A, Dazin PF, Shields R, Fu SM, Lanier LL. Functional competency of T cell antigen receptors in human thymus. J Immunol. 1987 Nov 15; 139(10):3245-50.