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. Vadstrup K, Galsgaard ED, Jensen H, Lanier LL, Ryan JC, Chen SY, Nolan GP, Vester-Andersen MK, Pedersen JS, Gerwien J, Jensen T, Bendtsen F. NKG2D ligand expression in Crohn's disease and NKG2D-dependent stimulation of CD8+ T cell migration. Exp Mol Pathol. 2017 08; 103(1):56-70.
  2. Mukherjee S, Jensen H, Stewart W, Stewart D, Ray WC, Chen SY, Nolan GP, Lanier LL, Das J. In silico modeling identifies CD45 as a regulator of IL-2 synergy in the NKG2D-mediated activation of immature human NK cells. Sci Signal. 2017 Jun 27; 10(485).
  3. Morvan MG, Champsaur M, Reizis B, Lanier LL. Chronic In Vivo Interaction of Dendritic Cells Expressing the Ligand Rae-1ε with NK Cells Impacts NKG2D Expression and Function. Immunohorizons. 2017 May 01; 1(3):10-19.
  4. Crome SQ, Nguyen LT, Lopez-Verges S, Yang SY, Martin B, Yam JY, Johnson DJ, Nie J, Pniak M, Yen PH, Milea A, Sowamber R, Katz SR, Bernardini MQ, Clarke BA, Shaw PA, Lang PA, Berman HK, Pugh TJ, Lanier LL, Ohashi PS. A distinct innate lymphoid cell population regulates tumor-associated T cells. Nat Med. 2017 Mar; 23(3):368-375.
  5. Jensen H, Chen SY, Folkersen L, Nolan GP, Lanier LL. EBI3 regulates the NK cell response to mouse cytomegalovirus infection. Proc Natl Acad Sci U S A. 2017 02 14; 114(7):1625-1630.
  6. Lam VC, Lanier LL. NK cells in host responses to viral infections. Curr Opin Immunol. 2017 Feb; 44:43-51.
  7. Nabekura T, Lanier LL. Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection. J Exp Med. 2016 11 14; 213(12):2745-2758.
  8. Nabekura T, Lanier LL. Activating Receptors for Self-MHC Class I Enhance Effector Functions and Memory Differentiation of NK Cells during Mouse Cytomegalovirus Infection. Immunity. 2016 07 19; 45(1):74-82.
  9. Spits H, Bernink JH, Lanier L. NK cells and type 1 innate lymphoid cells: partners in host defense. Nat Immunol. 2016 06 21; 17(7):758-64.
  10. Kohrt HE, Tumeh PC, Benson D, Bhardwaj N, Brody J, Formenti S, Fox BA, Galon J, June CH, Kalos M, Kirsch I, Kleen T, Kroemer G, Lanier L, Levy R, Lyerly HK, Maecker H, Marabelle A, Melenhorst J, Miller J, Melero I, Odunsi K, Palucka K, Peoples G, Ribas A, Robins H, Robinson W, Serafini T, Sondel P, Vivier E, Weber J, Wolchok J, Zitvogel L, Disis ML, Cheever MA, Cancer Immunotherapy Trials Network (CITN) . Immunodynamics: a cancer immunotherapy trials network review of immune monitoring in immuno-oncology clinical trials. J Immunother Cancer. 2016; 4:15.
  11. Cerwenka A, Lanier LL. Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol. 2016 Feb; 16(2):112-23.
  12. Madera S, Rapp M, Firth MA, Beilke JN, Lanier LL, Sun JC. Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide. J Exp Med. 2016 Feb 08; 213(2):225-33.
  13. Morvan MG, Lanier LL. NK cells and cancer: you can teach innate cells new tricks. Nat Rev Cancer. 2016 Jan; 16(1):7-19.
  14. Hendricks DW, Min-Oo G, Lanier LL. Sweet Is the Memory of Past Troubles: NK Cells Remember. Curr Top Microbiol Immunol. 2016; 395:147-71.
  15. Guan Z, Kuhn JA, Wang X, Colquitt B, Solorzano C, Vaman S, Guan AK, Evans-Reinsch Z, Braz J, Devor M, Abboud-Werner SL, Lanier LL, Lomvardas S, Basbaum AI. Injured sensory neuron-derived CSF1 induces microglial proliferation and DAP12-dependent pain. Nat Neurosci. 2016 Jan; 19(1):94-101.
  16. O'Sullivan TE, Sun JC, Lanier LL. Natural Killer Cell Memory. Immunity. 2015 Oct 20; 43(4):634-45.
  17. Huang X, Li J, Dorta-Estremera S, Di Domizio J, Anthony SM, Watowich SS, Popkin D, Liu Z, Brohawn P, Yao Y, Schluns KS, Lanier LL, Cao W. Neutrophils Regulate Humoral Autoimmunity by Restricting Interferon-γ Production via the Generation of Reactive Oxygen Species. Cell Rep. 2015 Aug 18; 12(7):1120-32.
  18. Lanier LL. NKG2D Receptor and Its Ligands in Host Defense. Cancer Immunol Res. 2015 Jun; 3(6):575-82.
  19. Nabekura T, Girard JP, Lanier LL. IL-33 receptor ST2 amplifies the expansion of NK cells and enhances host defense during mouse cytomegalovirus infection. J Immunol. 2015 Jun 15; 194(12):5948-52.
  20. Lee J, Zhang T, Hwang I, Kim A, Nitschke L, Kim M, Scott JM, Kamimura Y, Lanier LL, Kim S. Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals. Immunity. 2015 Mar 17; 42(3):431-42.
  21. Tanimura K, Jin H, Suenaga T, Morikami S, Arase N, Kishida K, Hirayasu K, Kohyama M, Ebina Y, Yasuda S, Horita T, Takasugi K, Ohmura K, Yamamoto K, Katayama I, Sasazuki T, Lanier LL, Atsumi T, Yamada H, Arase H. β2-Glycoprotein I/HLA class II complexes are novel autoantigens in antiphospholipid syndrome. Blood. 2015 Apr 30; 125(18):2835-44.
  22. Kamimura Y, Lanier LL. Homeostatic control of memory cell progenitors in the natural killer cell lineage. Cell Rep. 2015 Jan 13; 10(2):280-91.
  23. Min-Oo G, Lanier LL. Cytomegalovirus generates long-lived antigen-specific NK cells with diminished bystander activation to heterologous infection. J Exp Med. 2014 Dec 15; 211(13):2669-80.
  24. Nabekura T, Lanier LL. Antigen-specific expansion and differentiation of natural killer cells by alloantigen stimulation. J Exp Med. 2014 Nov 17; 211(12):2455-65.
  25. Weinger JG, Plaisted WC, Maciejewski SM, Lanier LL, Walsh CM, Lane TE. Activating receptor NKG2D targets RAE-1-expressing allogeneic neural precursor cells in a viral model of multiple sclerosis. Stem Cells. 2014 Oct; 32(10):2690-701.