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. Back to the future--defining NK cells and T cells. Eur J Immunol. 2007 Jun; 37(6):1424-6.
  2. Adams EJ, Juo ZS, Venook RT, Boulanger MJ, Arase H, Lanier LL, Garcia KC. Structural elucidation of the m157 mouse cytomegalovirus ligand for Ly49 natural killer cell receptors. Proc Natl Acad Sci U S A. 2007 Jun 12; 104(24):10128-33.
  3. Carr WH, Rosen DB, Arase H, Nixon DF, Michaelsson J, Lanier LL. Cutting Edge: KIR3DS1, a gene implicated in resistance to progression to AIDS, encodes a DAP12-associated receptor expressed on NK cells that triggers NK cell activation. J Immunol. 2007 Jan 15; 178(2):647-51.
  4. Kielczewska A, Kim HS, Lanier LL, Dimasi N, Vidal SM. Critical residues at the Ly49 natural killer receptor's homodimer interface determine functional recognition of m157, a mouse cytomegalovirus MHC class I-like protein. J Immunol. 2007 Jan 01; 178(1):369-77.
  5. Spits H, Lanier LL. Natural killer or dendritic: what's in a name? Immunity. 2007 Jan; 26(1):11-6.
  6. Takaki R, Watson SR, Lanier LL. DAP12: an adapter protein with dual functionality. Immunol Rev. 2006 Dec; 214:118-29.
  7. Berahovich RD, Lai NL, Wei Z, Lanier LL, Schall TJ. Evidence for NK cell subsets based on chemokine receptor expression. J Immunol. 2006 Dec 01; 177(11):7833-40.
  8. Lanier LL. Natural killer cells: roundup. Immunol Rev. 2006 Dec; 214:5-8.
  9. Mócsai A, Abram CL, Jakus Z, Hu Y, Lanier LL, Lowell CA. Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs. Nat Immunol. 2006 Dec; 7(12):1326-33.
  10. Hamerman JA, Jarjoura JR, Humphrey MB, Nakamura MC, Seaman WE, Lanier LL. Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. J Immunol. 2006 Aug 15; 177(4):2051-5.
  11. Lanier LL. Viral immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling in cell transformation and cancer. Trends Cell Biol. 2006 Aug; 16(8):388-90.
  12. Lodoen MB, Lanier LL. Natural killer cells as an initial defense against pathogens. Curr Opin Immunol. 2006 Aug; 18(4):391-8.
  13. Cao W, Rosen DB, Ito T, Bover L, Bao M, Watanabe G, Yao Z, Zhang L, Lanier LL, Liu YJ. Plasmacytoid dendritic cell-specific receptor ILT7-Fc epsilonRI gamma inhibits Toll-like receptor-induced interferon production. J Exp Med. 2006 Jun 12; 203(6):1399-405.
  14. Meresse B, Curran SA, Ciszewski C, Orbelyan G, Setty M, Bhagat G, Lee L, Tretiakova M, Semrad C, Kistner E, Winchester RJ, Braud V, Lanier LL, Geraghty DE, Green PH, Guandalini S, Jabri B. Reprogramming of CTLs into natural killer-like cells in celiac disease. J Exp Med. 2006 May 15; 203(5):1343-55.
  15. Hesslein DG, Takaki R, Hermiston ML, Weiss A, Lanier LL. Dysregulation of signaling pathways in CD45-deficient NK cells leads to differentially regulated cytotoxicity and cytokine production. Proc Natl Acad Sci U S A. 2006 May 02; 103(18):7012-7.
  16. Shiow LR, Rosen DB, Brdicková N, Xu Y, An J, Lanier LL, Cyster JG, Matloubian M. CD69 acts downstream of interferon-alpha/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature. 2006 Mar 23; 440(7083):540-4.
  17. Hamerman JA, Lanier LL. Inhibition of immune responses by ITAM-bearing receptors. Sci STKE. 2006 Jan 31; 2006(320):re1.
  18. Chan CW, Crafton E, Fan HN, Flook J, Yoshimura K, Skarica M, Brockstedt D, Dubensky TW, Stins MF, Lanier LL, Pardoll DM, Housseau F. Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity. Nat Med. 2006 Feb; 12(2):207-13.
  19. Bui JD, Carayannopoulos LN, Lanier LL, Yokoyama WM, Schreiber RD. IFN-dependent down-regulation of the NKG2D ligand H60 on tumors. J Immunol. 2006 Jan 15; 176(2):905-13.
  20. Vidal SM, Lanier LL. NK cell recognition of mouse cytomegalovirus-infected cells. Curr Top Microbiol Immunol. 2006; 298:183-206.
  21. Walsh KB, Lodoen MB, Lanier LL, Lane TE. NKG2D signaling and host defense after mouse hepatitis virus infection of the central nervous system. Adv Exp Med Biol. 2006; 581:369-72.
  22. Rosen DB, Bettadapura J, Alsharifi M, Mathew PA, Warren HS, Lanier LL. Cutting edge: lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A receptor. J Immunol. 2005 Dec 15; 175(12):7796-9.
  23. Chen S, Kawashima H, Lowe JB, Lanier LL, Fukuda M. Suppression of tumor formation in lymph nodes by L-selectin-mediated natural killer cell recruitment. J Exp Med. 2005 Dec 19; 202(12):1679-89.
  24. Humphrey MB, Lanier LL, Nakamura MC. Role of ITAM-containing adapter proteins and their receptors in the immune system and bone. Immunol Rev. 2005 Dec; 208:50-65.
  25. Routes JM, Ryan S, Morris K, Takaki R, Cerwenka A, Lanier LL. Adenovirus serotype 5 E1A sensitizes tumor cells to NKG2D-dependent NK cell lysis and tumor rejection. J Exp Med. 2005 Dec 05; 202(11):1477-82.