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. Calabrese DR, Chong T, Singer JP, Rajalingam R, Hays SR, Kukreja J, Leard L, Golden JA, Lanier LL, Greenland JR. CD16+ natural killer cells in bronchoalveolar lavage are associated with antibody-mediated rejection and chronic lung allograft dysfunction. Am J Transplant. 2023 Jan; 23(1):37-44.
  2. Aguilar OA, Gonzalez-Hinojosa MDR, Arakawa-Hoyt JS, Millan AJ, Gotthardt D, Nabekura T, Lanier LL. The CD16 and CD32b Fc-gamma receptors regulate antibody-mediated responses in mouse natural killer cells. J Leukoc Biol. 2023 Jan 10; 113(1):27-40.
  3. Calabrese DR, Tsao T, Magnen M, Valet C, Gao Y, Mallavia B, Tian JJ, Aminian EA, Wang KM, Shemesh A, Punzalan EB, Sarma A, Calfee CS, Christenson SA, Langelier CR, Hays SR, Golden JA, Leard LE, Kleinhenz ME, Kolaitis NA, Shah R, Venado A, Lanier LL, Greenland JR, Sayah DM, Ardehali A, Kukreja J, Weigt SS, Belperio JA, Singer JP, Looney MR. NKG2D receptor activation drives primary graft dysfunction severity and poor lung transplantation outcomes. JCI Insight. 2022 12 22; 7(24).
  4. Deuse T, Hu X, Gravina A, Wang D, Tediashvili G, De C, Thayer WO, Wahl A, Garcia JV, Reichenspurner H, Davis MM, Lanier LL, Schrepfer S. Author Correction: Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat Biotechnol. 2022 Nov; 40(11):1690.
  5. Vallejo J, Saigusa R, Gulati R, Suthahar SSA, Suryawanshi V, Alimadadi A, Durant CP, Ghosheh Y, Roy P, Ehinger E, Pattarabanjird T, Hanna DB, Landay AL, Tracy RP, Lazar JM, Mack WJ, Weber KM, Adimora AA, Hodis HN, Tien PC, Ofotokun I, Heath SL, Shemesh A, McNamara CA, Lanier LL, Hedrick CC, Kaplan RC, Ley K. Author Correction: Combined protein and transcript single-cell RNA sequencing in human peripheral blood mononuclear cells. BMC Biol. 2022 Oct 20; 20(1):237.
  6. Shemesh A, Su Y, Calabrese DR, Chen D, Arakawa-Hoyt J, Roybal KT, Heath JR, Greenland JR, Lanier LL. Diminished cell proliferation promotes natural killer cell adaptive-like phenotype by limiting FcεRIγ expression. J Exp Med. 2022 11 07; 219(11).
  7. Vallejo J, Saigusa R, Gulati R, Armstrong Suthahar SS, Suryawanshi V, Alimadadi A, Durant CP, Ghosheh Y, Roy P, Ehinger E, Pattarabanjird T, Hanna DB, Landay AL, Tracy RP, Lazar JM, Mack WJ, Weber KM, Adimora AA, Hodis HN, Tien PC, Ofotokun I, Heath SL, Shemesh A, McNamara CA, Lanier LL, Hedrick CC, Kaplan RC, Ley K. Combined protein and transcript single-cell RNA sequencing in human peripheral blood mononuclear cells. BMC Biol. 2022 09 01; 20(1):193.
  8. Saigusa R, Vallejo J, Gulati R, Suthahar SSA, Suryawanshi V, Alimadadi A, Makings J, Durant CP, Freuchet A, Roy P, Ghosheh Y, Pandori W, Pattarabanjird T, Drago F, Taylor A, McNamara CA, Shemesh A, Lanier LL, Hedrick CC, Ley K. Sex Differences in Coronary Artery Disease and Diabetes Revealed by scRNA-Seq and CITE-Seq of Human CD4+ T Cells. Int J Mol Sci. 2022 Aug 30; 23(17).
  9. Shemesh A, Pickering H, Roybal KT, Lanier LL. Differential IL-12 signaling induces human natural killer cell activating receptor-mediated ligand-specific expansion. J Exp Med. 2022 08 01; 219(8).
  10. Potempa M, Aguilar OA, Gonzalez-Hinojosa MDR, Tenvooren I, Marquez DM, Spitzer MH, Lanier LL. Influence of Self-MHC Class I Recognition on the Dynamics of NK Cell Responses to Cytomegalovirus Infection. J Immunol. 2022 04 01; 208(7):1742-1754.
  11. Aguilar OA, Fong LK, Ishiyama K, DeGrado WF, Lanier LL. The CD3ζ adaptor structure determines functional differences between human and mouse CD16 Fc receptor signaling. J Exp Med. 2022 05 02; 219(5).
  12. Ishiyama K, Arakawa-Hoyt J, Aguilar OA, Damm I, Towfighi P, Sigdel T, Tamaki S, Babdor J, Spitzer MH, Reed EF, Sarwal MM, Lanier LL, CMV Systems Immunobiology Group. Mass cytometry reveals single-cell kinetics of cytotoxic lymphocyte evolution in CMV-infected renal transplant patients. Proc Natl Acad Sci U S A. 2022 02 22; 119(8).
  13. Su Y, Yuan D, Chen DG, Ng RH, Wang K, Choi J, Li S, Hong S, Zhang R, Xie J, Kornilov SA, Scherler K, Pavlovitch-Bedzyk AJ, Dong S, Lausted C, Lee I, Fallen S, Dai CL, Baloni P, Smith B, Duvvuri VR, Anderson KG, Li J, Yang F, Duncombe CJ, McCulloch DJ, Rostomily C, Troisch P, Zhou J, Mackay S, DeGottardi Q, May DH, Taniguchi R, Gittelman RM, Klinger M, Snyder TM, Roper R, Wojciechowska G, Murray K, Edmark R, Evans S, Jones L, Zhou Y, Rowen L, Liu R, Chour W, Algren HA, Berrington WR, Wallick JA, Cochran RA, Micikas ME, ISB-Swedish COVID-19 Biobanking Unit, Wrin T, Petropoulos CJ, Cole HR, Fischer TD, Wei W, Hoon DSB, Price ND, Subramanian N, Hill JA, Hadlock J, Magis AT, Ribas A, Lanier LL, Boyd SD, Bluestone JA, Chu H, Hood L, Gottardo R, Greenberg PD, Davis MM, Goldman JD, Heath JR. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell. 2022 03 03; 185(5):881-895.e20.
  14. Good CR, Aznar MA, Kuramitsu S, Samareh P, Agarwal S, Donahue G, Ishiyama K, Wellhausen N, Rennels AK, Ma Y, Tian L, Guedan S, Alexander KA, Zhang Z, Rommel PC, Singh N, Glastad KM, Richardson MW, Watanabe K, Tanyi JL, O'Hara MH, Ruella M, Lacey SF, Moon EK, Schuster SJ, Albelda SM, Lanier LL, Young RM, Berger SL, June CH. An NK-like CAR T cell transition in CAR T cell dysfunction. Cell. 2021 12 09; 184(25):6081-6100.e26.
  15. Pickering H, Sen S, Arakawa-Hoyt J, Ishiyama K, Sun Y, Parmar R, Ahn RS, Sunga G, Llamas M, Hoffmann A, Deng M, Bunnapradist S, Schaenman JM, Gjertson DW, Rossetti M, Lanier LL, Reed EF, CMV Systems Immunobiology Group. NK and CD8+ T cell phenotypes predict onset and control of CMV viremia after kidney transplant. JCI Insight. 2021 11 08; 6(21).
  16. Kang E, Kadoch C, Rubenstein JL, Lanier LL, Wells JA. A functional mammalian display screen identifies rare antibodies that stimulate NK cell-mediated cytotoxicity. Proc Natl Acad Sci U S A. 2021 Aug 03; 118(31).
  17. Deuse T, Tediashvili G, Hu X, Gravina A, Tamenang A, Wang D, Connolly A, Mueller C, Mallavia B, Looney MR, Alawi M, Lanier LL, Schrepfer S. Hypoimmune induced pluripotent stem cell-derived cell therapeutics treat cardiovascular and pulmonary diseases in immunocompetent allogeneic mice. Proc Natl Acad Sci U S A. 2021 Jul 13; 118(28).
  18. Deuse T, Hu X, Agbor-Enoh S, Jang MK, Alawi M, Saygi C, Gravina A, Tediashvili G, Nguyen VQ, Liu Y, Valantine H, Lanier LL, Schrepfer S. The SIRPα-CD47 immune checkpoint in NK cells. J Exp Med. 2021 03 01; 218(3).
  19. Calabrese DR, Aminian E, Mallavia B, Liu F, Cleary SJ, Aguilar OA, Wang P, Singer JP, Hays SR, Golden JA, Kukreja J, Dugger D, Nakamura M, Lanier LL, Looney MR, Greenland JR. Natural killer cells activated through NKG2D mediate lung ischemia-reperfusion injury. J Clin Invest. 2021 02 01; 131(3).
  20. Adams NM, Diaz-Salazar C, Dang C, Lanier LL, Sun JC. Cutting Edge: Heterogeneity in Cell Age Contributes to Functional Diversity of NK Cells. J Immunol. 2021 02 01; 206(3):465-470.
  21. Casanova JL, Holtzman DM, Kaech SM, Lanier LL, Nathan CF, Rudensky AY, Tuveson D, Wolchok JD. Immigration in science. J Exp Med. 2020 11 02; 217(11).
  22. Su Y, Chen D, Yuan D, Lausted C, Choi J, Dai CL, Voillet V, Duvvuri VR, Scherler K, Troisch P, Baloni P, Qin G, Smith B, Kornilov SA, Rostomily C, Xu A, Li J, Dong S, Rothchild A, Zhou J, Murray K, Edmark R, Hong S, Heath JE, Earls J, Zhang R, Xie J, Li S, Roper R, Jones L, Zhou Y, Rowen L, Liu R, Mackay S, O'Mahony DS, Dale CR, Wallick JA, Algren HA, Zager MA, ISB-Swedish COVID19 Biobanking Unit , Wei W, Price ND, Huang S, Subramanian N, Wang K, Magis AT, Hadlock JJ, Hood L, Aderem A, Bluestone JA, Lanier LL, Greenberg PD, Gottardo R, Davis MM, Goldman JD, Heath JR. Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19. Cell. 2020 12 10; 183(6):1479-1495.e20.
  23. Aguilar OA, Tanaka M, Balaji GR, Berry R, Rossjohn J, Lanier LL, Carlyle JR. Tetramer Immunization and Selection Followed by CELLISA Screening to Generate Monoclonal Antibodies against the Mouse Cytomegalovirus m12 Immunoevasin. J Immunol. 2020 09 15; 205(6):1709-1717.
  24. Su Y, Chen D, Lausted C, Yuan D, Choi J, Dai C, Voillet V, Scherler K, Troisch P, Duvvuri VR, Baloni P, Qin G, Smith B, Kornilov S, Rostomily C, Xu A, Li J, Dong S, Rothchild A, Zhou J, Murray K, Edmark R, Hong S, Jones L, Zhou Y, Roper R, Mackay S, O'Mahony DS, Dale CR, Wallick JA, Algren HA, Michael ZA, Magis A, Wei W, Price ND, Huang S, Subramanian N, Wang K, Hadlock J, Hood L, Aderem A, Bluestone JA, Lanier LL, Greenberg P, Gottardo R, Davis MM, Goldman JD, Heath JR. Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories. bioRxiv. 2020 Jul 31.
  25. Guerra N, Lanier LL. Editorial: Emerging Concepts on the NKG2D Receptor-Ligand Axis in Health and Diseases. Front Immunol. 2020; 11:562.