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. Hesslein DG, Lanier LL. Transcriptional control of natural killer cell development and function. Adv Immunol. 2011; 109:45-85.
  2. Sun JC, Lanier LL. Versatility in NK cell memory. Immunol Cell Biol. 2011 Mar; 89(3):327-9.
  3. Orr MT, Wu J, Fang M, Sigal LJ, Spee P, Egebjerg T, Dissen E, Fossum S, Phillips JH, Lanier LL. Development and function of CD94-deficient natural killer cells. PLoS One. 2010 Dec 03; 5(12):e15184.
  4. Babic M, Pyzik M, Zafirova B, Mitrovic M, Butorac V, Lanier LL, Krmpotic A, Vidal SM, Jonjic S. Cytomegalovirus immunoevasin reveals the physiological role of "missing self" recognition in natural killer cell dependent virus control in vivo. J Exp Med. 2010 Nov 22; 207(12):2663-73.
  5. Orr MT, Lanier LL. Natural killer cell education and tolerance. Cell. 2010 Sep 17; 142(6):847-56.
  6. Bezman NA, Cedars E, Steiner DF, Blelloch R, Hesslein DG, Lanier LL. Distinct requirements of microRNAs in NK cell activation, survival, and function. J Immunol. 2010 Oct 01; 185(7):3835-46.
  7. Beilke JN, Benjamin J, Lanier LL. The requirement for NKG2D in NK cell-mediated rejection of parental bone marrow grafts is determined by MHC class I expressed by the graft recipient. Blood. 2010 Dec 09; 116(24):5208-16.
  8. B Gurfein, A Stamm, P Bacchetti, M Dallman, N Nadkarni, J Milush, C Touma, R Palme, C Pozzo Di Borgo, G Fromentin, R Lown-Hecht, J Konsman, M Acree, M Premenko-Lanier, N Darcel, F Hecht, D Nixon. P01.43. The calm mouse: an animal model of stress reduction. BMC Complementary and Alternative Medicine. 2012 Jun 1; 12(Suppl 1):p43.
  9. Orr MT, Beilke JN, Proekt I, Lanier LL. Natural killer cells in NOD.NK1.1 mice acquire cytolytic function during viral infection and provide protection against cytomegalovirus. Proc Natl Acad Sci U S A. 2010 Sep 07; 107(36):15844-9.
  10. Sun JC, Beilke JN, Lanier LL. Immune memory redefined: characterizing the longevity of natural killer cells. Immunol Rev. 2010 Jul; 236:83-94.
  11. Champsaur M, Beilke JN, Ogasawara K, Koszinowski UH, Jonjic S, Lanier LL. Intact NKG2D-independent function of NK cells chronically stimulated with the NKG2D ligand Rae-1. J Immunol. 2010 Jul 01; 185(1):157-65.
  12. Champsaur M, Lanier LL. Effect of NKG2D ligand expression on host immune responses. Immunol Rev. 2010 May; 235(1):267-85.
  13. Koth LL, Cambier CJ, Ellwanger A, Solon M, Hou L, Lanier LL, Abram CL, Hamerman JA, Woodruff PG. DAP12 is required for macrophage recruitment to the lung in response to cigarette smoke and chemotaxis toward CCL2. J Immunol. 2010 Jun 01; 184(11):6522-8.
  14. Orr MT, Murphy WJ, Lanier LL. 'Unlicensed' natural killer cells dominate the response to cytomegalovirus infection. Nat Immunol. 2010 Apr; 11(4):321-7.
  15. Crane CA, Han SJ, Barry JJ, Ahn BJ, Lanier LL, Parsa AT. TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients. Neuro Oncol. 2010 Jan; 12(1):7-13.
  16. Wang J, Fan Q, Satoh T, Arii J, Lanier LL, Spear PG, Kawaguchi Y, Arase H. Binding of herpes simplex virus glycoprotein B (gB) to paired immunoglobulin-like type 2 receptor alpha depends on specific sialylated O-linked glycans on gB. J Virol. 2009 Dec; 83(24):13042-5.
  17. Jenne CN, Enders A, Rivera R, Watson SR, Bankovich AJ, Pereira JP, Xu Y, Roots CM, Beilke JN, Banerjee A, Reiner SL, Miller SA, Weinmann AS, Goodnow CC, Lanier LL, Cyster JG, Chun J. T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow. J Exp Med. 2009 Oct 26; 206(11):2469-81.
  18. Gurfein BT, Stamm AW, Bacchetti P, Dallman MF, Nadkarni NA, Milush JM, Touma C, Palme R, Di Borgo CP, Fromentin G, Lown-Hecht R, Konsman JP, Acree M, Premenko-Lanier M, Darcel N, Hecht FM, Nixon DF. The calm mouse: an animal model of stress reduction. Mol Med. 2012 May 09; 18:606-17.
  19. Long BR, Erickson AE, Chapman JM, Barbour JD, Vu BA, Ho EL, Lanier LL, Sauer MM, Carvalho KI, Nixon DF, Kallas EG. Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2. Immunology. 2010 Feb; 129(2):186-96.
  20. Sun JC, Lanier LL. Natural killer cells remember: an evolutionary bridge between innate and adaptive immunity? Eur J Immunol. 2009 Aug; 39(8):2059-64.
  21. Sun JC, Ma A, Lanier LL. Cutting edge: IL-15-independent NK cell response to mouse cytomegalovirus infection. J Immunol. 2009 Sep 01; 183(5):2911-4.
  22. Cao W, Bover L, Cho M, Wen X, Hanabuchi S, Bao M, Rosen DB, Wang YH, Shaw JL, Du Q, Li C, Arai N, Yao Z, Lanier LL, Liu YJ. Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. J Exp Med. 2009 Jul 06; 206(7):1603-14.
  23. Lanier LL, Sun JC. Do the terms innate and adaptive immunity create conceptual barriers? Nat Rev Immunol. 2009 May; 9(5):302-3.
  24. Orr MT, Sun JC, Hesslein DG, Arase H, Phillips JH, Takai T, Lanier LL. Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection. J Exp Med. 2009 Apr 13; 206(4):807-17.
  25. Kielczewska A, Pyzik M, Sun T, Krmpotic A, Lodoen MB, Munks MW, Babic M, Hill AB, Koszinowski UH, Jonjic S, Lanier LL, Vidal SM. Ly49P recognition of cytomegalovirus-infected cells expressing H2-Dk and CMV-encoded m04 correlates with the NK cell antiviral response. J Exp Med. 2009 Mar 16; 206(3):515-23.