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. Dogra P, Rancan C, Ma W, Toth M, Senda T, Carpenter DJ, Kubota M, Matsumoto R, Thapa P, Szabo PA, Li Poon MM, Li J, Arakawa-Hoyt J, Shen Y, Fong L, Lanier LL, Farber DL. Tissue Determinants of Human NK Cell Development, Function, and Residence. Cell. 2020 02 20; 180(4):749-763.e13.
  2. Zammit NW, Siggs OM, Gray PE, Horikawa K, Langley DB, Walters SN, Daley SR, Loetsch C, Warren J, Yap JY, Cultrone D, Russell A, Malle EK, Villanueva JE, Cowley MJ, Gayevskiy V, Dinger ME, Brink R, Zahra D, Chaudhri G, Karupiah G, Whittle B, Roots C, Bertram E, Yamada M, Jeelall Y, Enders A, Clifton BE, Mabbitt PD, Jackson CJ, Watson SR, Jenne CN, Lanier LL, Wiltshire T, Spitzer MH, Nolan GP, Schmitz F, Aderem A, Porebski BT, Buckle AM, Abbott DW, Ziegler JB, Craig ME, Benitez-Aguirre P, Teo J, Tangye SG, King C, Wong M, Cox MP, Phung W, Tang J, Sandoval W, Wertz IE, Christ D, Goodnow CC, Grey ST. Denisovan, modern human and mouse TNFAIP3 alleles tune A20 phosphorylation and immunity. Nat Immunol. 2019 10; 20(10):1299-1310.
  3. Lee BH, Kelly G, Bradford S, Davila M, Guo XV, Amir ED, Thrash EM, Solga MD, Lannigan J, Sellers B, Candia J, Tsang J, Montgomery RR, Tamaki SJ, Sigdel TK, Sarwal MM, Lanier LL, Tian Y, Kim C, Hinz D, Peters B, Sette A, Rahman AH. A Modified Injector and Sample Acquisition Protocol Can Improve Data Quality and Reduce Inter-Instrument Variability of the Helios Mass Cytometer. Cytometry A. 2019 09; 95(9):1019-1030.
  4. McKechnie JL, Beltrán D, Pitti A, Saenz L, Araúz AB, Vergara R, Harris E, Lanier LL, Blish CA, López-Vergès S. HLA Upregulation During Dengue Virus Infection Suppresses the Natural Killer Cell Response. Front Cell Infect Microbiol. 2019; 9:268.
  5. Lanier LL. Plastic fantastic innate lymphoid cells. J Exp Med. 2019 08 05; 216(8):1726-1727.
  6. Lam VC, Folkersen L, Aguilar OA, Lanier LL. KLF12 Regulates Mouse NK Cell Proliferation. J Immunol. 2019 08 15; 203(4):981-989.
  7. Feng Y, Daley-Bauer LP, Roback L, Guo H, Koehler HS, Potempa M, Lanier LL, Mocarski ES. Caspase-8 restricts antiviral CD8 T cell hyperaccumulation. Proc Natl Acad Sci U S A. 2019 07 23; 116(30):15170-15177.
  8. Feng Y, Daley-Bauer LP, Roback L, Potempa M, Lanier LL, Mocarski ES. Caspase-8 restricts natural killer cell accumulation during MCMV Infection. Med Microbiol Immunol. 2019 Aug; 208(3-4):543-554.
  9. Das J, Lanier LL. Data analysis to modeling to building theory in NK cell biology and beyond: How can computational modeling contribute? J Leukoc Biol. 2019 06; 105(6):1305-1317.
  10. Calabrese DR, Chong T, Wang A, Singer JP, Gottschall M, Hays SR, Golden JA, Kukreja J, Lanier LL, Tang Q, Greenland JR. NKG2C Natural Killer Cells in Bronchoalveolar Lavage Are Associated With Cytomegalovirus Viremia and Poor Outcomes in Lung Allograft Recipients. Transplantation. 2019 03; 103(3):493-501.
  11. 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. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat Biotechnol. 2019 03; 37(3):252-258.
  12. Balaji GR, Aguilar OA, Tanaka M, Shingu-Vazquez MA, Fu Z, Gully BS, Lanier LL, Carlyle JR, Rossjohn J, Berry R. Recognition of host Clr-b by the inhibitory NKR-P1B receptor provides a basis for missing-self recognition. Nat Commun. 2018 11 05; 9(1):4623.
  13. Calabrese DR, Lanier LL, Greenland JR. Natural killer cells in lung transplantation. Thorax. 2019 04; 74(4):397-404.
  14. Sun JC, Lanier LL. Is There Natural Killer Cell Memory and Can It Be Harnessed by Vaccination? NK Cell Memory and Immunization Strategies against Infectious Diseases and Cancer. Cold Spring Harb Perspect Biol. 2018 10 01; 10(10).
  15. Balin SJ, Pellegrini M, Klechevsky E, Won ST, Weiss DI, Choi AW, Hakimian J, Lu J, Ochoa MT, Bloom BR, Lanier LL, Stenger S, Modlin RL. Human antimicrobial cytotoxic T lymphocytes, defined by NK receptors and antimicrobial proteins, kill intracellular bacteria. Sci Immunol. 2018 08 31; 3(26).
  16. Trotta E, Bessette PH, Silveria SL, Ely LK, Jude KM, Le DT, Holst CR, Coyle A, Potempa M, Lanier LL, Garcia KC, Crellin NK, Rondon IJ, Bluestone JA. A human anti-IL-2 antibody that potentiates regulatory T cells by a structure-based mechanism. Nat Med. 2018 07; 24(7):1005-1014.
  17. Nabekura T, Chen Z, Schroeder C, Park T, Vivier E, Lanier LL, Liu D. Crk Adaptor Proteins Regulate NK Cell Expansion and Differentiation during Mouse Cytomegalovirus Infection. J Immunol. 2018 05 15; 200(10):3420-3428.
  18. Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T. Pillars Article: Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA. Science. 1999. 285: 727-729. J Immunol. 2018 04 01; 200(7):2231-2233.
  19. Cerwenka A, Lanier LL. Natural killers join the fight against cancer. Science. 2018 03 30; 359(6383):1460-1461.
  20. Méndez-Lagares G, Lu D, Chen C, Terrault N, Segal MR, Khalili M, Monto A, Shen H, Manos MM, Lanier LL, Ryan JC, McCune JM, Hartigan-O'Connor DJ. Memory T Cell Proliferation before Hepatitis C Virus Therapy Predicts Antiviral Immune Responses and Treatment Success. J Immunol. 2018 02 01; 200(3):1124-1132.
  21. Pan YG, Yu YL, Lin CC, Lanier LL, Chu CL. FcεRI γ-Chain Negatively Modulates Dectin-1 Responses in Dendritic Cells. Front Immunol. 2017; 8:1424.
  22. Mukherjee S, Stewart D, Stewart W, Lanier LL, Das J. Connecting the dots across time: reconstruction of single-cell signalling trajectories using time-stamped data. R Soc Open Sci. 2017 Aug; 4(8):170811.
  23. Jensen H, Potempa M, Gotthardt D, Lanier LL. Cutting Edge: IL-2-Induced Expression of the Amino Acid Transporters SLC1A5 and CD98 Is a Prerequisite for NKG2D-Mediated Activation of Human NK Cells. J Immunol. 2017 09 15; 199(6):1967-1972.
  24. Nabekura T, Gotthardt D, Niizuma K, Trsan T, Jenus T, Jonjic S, Lanier LL. Cutting Edge: NKG2D Signaling Enhances NK Cell Responses but Alone Is Insufficient To Drive Expansion during Mouse Cytomegalovirus Infection. J Immunol. 2017 09 01; 199(5):1567-1571.
  25. Hosomi S, Grootjans J, Tschurtschenthaler M, Krupka N, Matute JD, Flak MB, Martinez-Naves E, Gomez Del Moral M, Glickman JN, Ohira M, Lanier LL, Kaser A, Blumberg R. Intestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up-regulation and NKG2D-mediated inflammation. J Exp Med. 2017 Oct 02; 214(10):2985-2997.