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. Just the FACS. J Immunol. 2014 Sep 01; 193(5):2043-4.
  2. Crane CA, Austgen K, Haberthur K, Hofmann C, Moyes KW, Avanesyan L, Fong L, Campbell MJ, Cooper S, Oakes SA, Parsa AT, Lanier LL. Immune evasion mediated by tumor-derived lactate dehydrogenase induction of NKG2D ligands on myeloid cells in glioblastoma patients. Proc Natl Acad Sci U S A. 2014 Sep 02; 111(35):12823-8.
  3. Du J, Lopez-Verges S, Pitcher BN, Johnson J, Jung SH, Zhou L, Hsu K, Czuczman MS, Cheson B, Kaplan L, Lanier LL, Venstrom JM. CALGB 150905 (Alliance): rituximab broadens the antilymphoma response by activating unlicensed NK cells. Cancer Immunol Res. 2014 Sep; 2(9):878-89.
  4. Min-Oo G, Bezman NA, Madera S, Sun JC, Lanier LL. Proapoptotic Bim regulates antigen-specific NK cell contraction and the generation of the memory NK cell pool after cytomegalovirus infection. J Exp Med. 2014 Jun 30; 211(7):1289-96.
  5. Orbelyan GA, Tang F, Sally B, Solus J, Meresse B, Ciszewski C, Grenier JC, Barreiro LB, Lanier LL, Jabri B. Human NKG2E is expressed and forms an intracytoplasmic complex with CD94 and DAP12. J Immunol. 2014 Jul 15; 193(2):610-6.
  6. Kalinowski A, Ueki I, Min-Oo G, Ballon-Landa E, Knoff D, Galen B, Lanier LL, Nadel JA, Koff JL. EGFR activation suppresses respiratory virus-induced IRF1-dependent CXCL10 production. . 2014 Jul 15; 307(2):L186-96.
  7. Kamimura Y, Lanier LL. Rapid and sequential quantitation of salivary gland-associated mouse cytomegalovirus in oral lavage. J Virol Methods. 2014 09 01; 205:53-6.
  8. Hendricks DW, Balfour HH, Dunmire SK, Schmeling DO, Hogquist KA, Lanier LL. Cutting edge: NKG2C(hi)CD57+ NK cells respond specifically to acute infection with cytomegalovirus and not Epstein-Barr virus. J Immunol. 2014 May 15; 192(10):4492-6.
  9. Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, Shi K, Toyama-Sorimachi N, Yasuda S, Horita T, Hiwa R, Takasugi K, Ohmura K, Yoshikawa H, Saito T, Atsumi T, Sasazuki T, Katayama I, Lanier LL, Arase H. Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility. Proc Natl Acad Sci U S A. 2014 Mar 11; 111(10):3787-92.
  10. Lanier LL. Of snowflakes and natural killer cell subsets. Nat Biotechnol. 2014 Feb; 32(2):140-2.
  11. Nabekura T, Kanaya M, Shibuya A, Fu G, Gascoigne NR, Lanier LL. Costimulatory molecule DNAM-1 is essential for optimal differentiation of memory natural killer cells during mouse cytomegalovirus infection. Immunity. 2014 Feb 20; 40(2):225-34.
  12. Dangl JL, Lanier LL. Founding father of FACS: Professor Leonard A. Herzenberg (1931–2013). Proc Natl Acad Sci U S A. 2013 Dec 24; 110(52):20848-9.
  13. Milush JM, López-Vergès S, York VA, Deeks SG, Martin JN, Hecht FM, Lanier LL, Nixon DF. CD56negCD16⁺ NK cells are activated mature NK cells with impaired effector function during HIV-1 infection. Retrovirology. 2013 Dec 18; 10:158.
  14. Hartigan-O'Connor DJ, Lin D, Ryan JC, Shvachko VA, Cozen ML, Segal MR, Terrault NA, Lanier LL, Manos MM, McCune JM. Monocyte activation by interferon α is associated with failure to achieve a sustained virologic response after treatment for hepatitis C virus infection. J Infect Dis. 2014 May 15; 209(10):1602-12.
  15. Kim CC, Lanier LL. Beyond the transcriptome: completion of act one of the Immunological Genome Project. Curr Opin Immunol. 2013 Oct; 25(5):593-7.
  16. Ueki IF, Min-Oo G, Kalinowski A, Ballon-Landa E, Lanier LL, Nadel JA, Koff JL. Respiratory virus-induced EGFR activation suppresses IRF1-dependent interferon λ and antiviral defense in airway epithelium. J Exp Med. 2013 Sep 23; 210(10):1929-36.
  17. Co EC, Gormley M, Kapidzic M, Rosen DB, Scott MA, Stolp HA, McMaster M, Lanier LL, Bárcena A, Fisher SJ. Maternal decidual macrophages inhibit NK cell killing of invasive cytotrophoblasts during human pregnancy. Biol Reprod. 2013 Jun; 88(6):155.
  18. Hosomi S, Chen Z, Baker K, Chen L, Huang YH, Olszak T, Zeissig S, Wang JH, Mandelboim O, Beauchemin N, Lanier LL, Blumberg RS. CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function and signaling. Eur J Immunol. 2013 Sep; 43(9):2473-83.
  19. Mingueneau M, Kreslavsky T, Gray D, Heng T, Cruse R, Ericson J, Bendall S, Spitzer MH, Nolan GP, Kobayashi K, von Boehmer H, Mathis D, Benoist C, Immunological Genome Consortium , Best AJ, Knell J, Goldrath A, Joic V, Koller D, Shay T, Regev A, Cohen N, Brennan P, Brenner M, Kim F, Nageswara Rao T, Wagers A, Heng T, Ericson J, Rothamel K, Ortiz-Lopez A, Mathis D, Benoist C, Bezman NA, Sun JC, Min-Oo G, Kim CC, Lanier LL, Miller J, Brown B, Merad M, Gautier EL, Jakubzick C, Randolph GJ, Monach P, Blair DA, Dustin ML, Shinton SA, Hardy RR, Laidlaw D, Collins J, Gazit R, Rossi DJ, Malhotra N, Sylvia K, Kang J, Kreslavsky T, Fletcher A, Elpek K, Bellemare-Pelletier A, Malhotra D, Turley S. The transcriptional landscape of αβ T cell differentiation. Nat Immunol. 2013 Jun; 14(6):619-32.
  20. Beaulieu AM, Bezman NA, Lee JE, Matloubian M, Sun JC, Lanier LL. MicroRNA function in NK-cell biology. Immunol Rev. 2013 May; 253(1):40-52.
  21. Jojic V, Shay T, Sylvia K, Zuk O, Sun X, Kang J, Regev A, Koller D, Immunological Genome Project Consortium , Best AJ, Knell J, Goldrath A, Joic V, Koller D, Shay T, Regev A, Cohen N, Brennan P, Brenner M, Kim F, Rao TN, Wagers A, Heng T, Ericson J, Rothamel K, Ortiz-Lopez A, Mathis D, Benoist C, Bezman NA, Sun JC, Min-Oo G, Kim CC, Lanier LL, Miller J, Brown B, Merad M, Gautier EL, Jakubzick C, Randolph GJ, Monach P, Blair DA, Dustin ML, Shinton SA, Hardy RR, Laidlaw D, Collins J, Gazit R, Rossi DJ, Malhotra N, Sylvia K, Kang J, Kreslavsky T, Fletcher A, Elpek K, Bellemarte-Pelletier A, Malhotra D, Turley S. Identification of transcriptional regulators in the mouse immune system. Nat Immunol. 2013 Jun; 14(6):633-43.
  22. Zawislak CL, Beaulieu AM, Loeb GB, Karo J, Canner D, Bezman NA, Lanier LL, Rudensky AY, Sun JC. Stage-specific regulation of natural killer cell homeostasis and response against viral infection by microRNA-155. Proc Natl Acad Sci U S A. 2013 Apr 23; 110(17):6967-72.
  23. Min-Oo G, Kamimura Y, Hendricks DW, Nabekura T, Lanier LL. Natural killer cells: walking three paths down memory lane. Trends Immunol. 2013 Jun; 34(6):251-8.
  24. Lanier LL. Shades of grey--the blurring view of innate and adaptive immunity. Nat Rev Immunol. 2013 02; 13(2):73-4.
  25. Jiang Y, Arase N, Kohyama M, Hirayasu K, Suenaga T, Jin H, Matsumoto M, Shida K, Lanier LL, Saito T, Arase H. Transport of misfolded endoplasmic reticulum proteins to the cell surface by MHC class II molecules. Int Immunol. 2013 Apr; 25(4):235-46.