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. Shiratori I, Ogasawara K, Saito T, Lanier LL, Arase H. Activation of natural killer cells and dendritic cells upon recognition of a novel CD99-like ligand by paired immunoglobulin-like type 2 receptor. J Exp Med. 2004 Feb 16; 199(4):525-33.
  2. Hamerman JA, Ogasawara K, Lanier LL. Cutting edge: Toll-like receptor signaling in macrophages induces ligands for the NKG2D receptor. J Immunol. 2004 Feb 15; 172(4):2001-5.
  3. Humphrey MB, Ogasawara K, Yao W, Spusta SC, Daws MR, Lane NE, Lanier LL, Nakamura MC. The signaling adapter protein DAP12 regulates multinucleation during osteoclast development. J Bone Miner Res. 2004 Feb; 19(2):224-34.
  4. Lanier LL. NKG2D. J Biol Regul Homeost Agents. 2003 Oct-Dec; 17(4):338-40.
  5. Meyaard L, van der Vuurst de Vries AR, de Ruiter T, Lanier LL, Phillips JH, Clevers H. Retraction. J Exp Med. 2003 Oct 06; 198(7):1129.
  6. Westgaard IH, Dissen E, Torgersen KM, Lazetic S, Lanier LL, Phillips JH, Fossum S. The lectin-like receptor KLRE1 inhibits natural killer cell cytotoxicity. J Exp Med. 2003 Jun 02; 197(11):1551-61.
  7. Lanier LL. Natural killer cell receptor signaling. Curr Opin Immunol. 2003 Jun; 15(3):308-14.
  8. Lodoen M, Ogasawara K, Hamerman JA, Arase H, Houchins JP, Mocarski ES, Lanier LL. NKG2D-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules. J Exp Med. 2003 May 19; 197(10):1245-53.
  9. Zompi S, Hamerman JA, Ogasawara K, Schweighoffer E, Tybulewicz VL, Di Santo JP, Lanier LL, Colucci F. NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases. Nat Immunol. 2003 Jun; 4(6):565-72.
  10. Cerwenka A, Lanier LL. NKG2D ligands: unconventional MHC class I-like molecules exploited by viruses and cancer. Tissue Antigens. 2003 May; 61(5):335-43.
  11. Cooper MD, Lanier LL, Conley ME, Puck JM. Immunodeficiency disorders. Hematology Am Soc Hematol Educ Program. 2003; 314-30.
  12. Ogasawara K, Hamerman JA, Hsin H, Chikuma S, Bour-Jordan H, Chen T, Pertel T, Carnaud C, Bluestone JA, Lanier LL. Impairment of NK cell function by NKG2D modulation in NOD mice. Immunity. 2003 Jan; 18(1):41-51.
  13. Wu J, Lanier LL. Natural killer cells and cancer. Adv Cancer Res. 2003; 90:127-56.
  14. Michaëlsson J, Teixeira de Matos C, Achour A, Lanier LL, Kärre K, Söderström K. A signal peptide derived from hsp60 binds HLA-E and interferes with CD94/NKG2A recognition. J Exp Med. 2002 Dec 02; 196(11):1403-14.
  15. Arase H, Lanier LL. Virus-driven evolution of natural killer cell receptors. Microbes Infect. 2002 Dec; 4(15):1505-12.
  16. Ogasawara K, Yoshinaga SK, Lanier LL. Inducible costimulator costimulates cytotoxic activity and IFN-gamma production in activated murine NK cells. J Immunol. 2002 Oct 01; 169(7):3676-85.
  17. Naper C, Hayashi S, Kveberg L, Niemi EC, Lanier LL, Vaage JT, Ryan JC. Ly-49s3 is a promiscuous activating rat NK cell receptor for nonclassical MHC class I-encoded target ligands. J Immunol. 2002 Jul 01; 169(1):22-30.
  18. Arase H, Mocarski ES, Campbell AE, Hill AB, Lanier LL. Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science. 2002 May 17; 296(5571):1323-6.
  19. Cerwenka A, O'Callaghan CA, Hamerman JA, Yadav R, Ajayi W, Roopenian DC, Joyce S, Lanier LL. Cutting edge: the minor histocompatibility antigen H60 peptide interacts with both H-2Kb and NKG2D. J Immunol. 2002 Apr 01; 168(7):3131-4.
  20. Masuda H, Saeki Y, Nomura M, Shida K, Matsumoto M, Ui M, Lanier LL, Seya T. High levels of RAE-1 isoforms on mouse tumor cell lines assessed by anti-"pan" RAE-1 antibody confer tumor susceptibility to NK cells. Biochem Biophys Res Commun. 2002 Jan 11; 290(1):140-5.
  21. Lanier LL. A renaissance for the tumor immunosurveillance hypothesis. Nat Med. 2001 Nov; 7(11):1178-80.
  22. Cerwenka A, Lanier LL. Natural killer cells, viruses and cancer. Nat Rev Immunol. 2001 Oct; 1(1):41-9.
  23. Cerwenka A, Baron JL, Lanier LL. Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo. Proc Natl Acad Sci U S A. 2001 Sep 25; 98(20):11521-6.
  24. Smith WL, Collins J, Lanier L, Rao VM. Initiative of the Council of Academic Societies. Redefining scholarship in academic radiology. Acad Radiol. 2001 Sep; 8(9):919-21.
  25. Warren HS, Campbell AJ, Waldron JC, Lanier LL. Biphasic response of NK cells expressing both activating and inhibitory killer Ig-like receptors. Int Immunol. 2001 Aug; 13(8):1043-52.