We are interested in the role of natural killer (NK) cells in immunity and reproduction. NK cells have also proven to be a very useful tool to study certain fundamental processes. For example, we have gained unique insights into cytotoxic immunological synapses, signaling by integrins, and regulation of cellular function by inhibitory receptors. We integrate quantitative proteomics and imaging with cellular and biochemical techniques to understand the molecular basis of NK cell regulation.
One of our main goals is to understand how signaling by inhibitory receptors controls NK cell biology. We have shown how NK inhibitory receptors recruit a specific phosphatase to block activation signals. We have recently identified a new signal transmitted by inhibitory receptors and are studying how it regulates NK responses. NK inhibitory receptors serve to prevent killing of healthy cells, but they also provide signals for NK cell licensing. We wish to understand the molecular basis for NK cell licensing.
NK cells provide a unique opportunity to study signal transduction by integrins. In contrast to T cells, NK cells receive signals directly from integrin LFA-1, independently of signaling by other receptors. LFA-1 signaling in NK cells induces polarization of lytic granules toward target cells. We are dissecting the signaling pathways for integrin-dependent granule polarization and for degranulation induced by NK activation receptors.
We are interested in the function of NK cells during early pregnancy. NK cells respond to fetal soluble HLA-G by promoting vascular remodeling, which is required for proper blood supply to the fetus. Read more about it on this page.
Little is known about the role of NK cells in malaria and the phenotype and activation status of NK cells during Plasmodium falciparum infection. In collaboration with other groups in the NIAID Malaria Research Program, we are using mice and human samples to study the response of NK cells to Plasmodium parasite infection at both the liver and the blood stage and to determine how NK responses may contribute to protective immunity. We are also performing longitudinal studies of NK cells from a cohort of individuals in malaria-endemic areas. Such a systematic analysis of NK cells from the same individuals during dry and wet seasons will provide valuable insights into NK cell function in malaria. See more about the Malaria Research Program.
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Dr. Long graduated in biochemistry from the ETH Zürich, Switzerland, spent a year as a postbac at the MRC Department of Molecular Genetics, University of Edinburgh, and obtained a Ph.D. in biology from the University of Geneva, Switzerland. After postdoctoral research at the department of embryology, Carnegie Institution, in Baltimore, and at the National Cancer Institute, National Institutes of Health, he returned to Geneva as a junior faculty in the medical school’s department of microbiology. There he began to apply molecular approaches to study MHC class II molecules and processing pathways for antigen presentation to CD4 T cells. He was recruited to the Laboratory of Immunogenetics, NIAID, in 1983, where he has remained to this day. In 1988, he became a tenured investigator and chief of the Molecular and Cellular Immunology Section. In 1995, his research interest shifted from antigen presentation to the regulation of natural killer (NK) cell activation, when his team identified molecular clones for the inhibitory killer cell Ig-like receptors (KIR) and the signaling basis for inhibition.
Sumati Rajagopalan, Ph.D., Staff Scientist
Mary E. Peterson, BiologistMinggang Zhang, Postdoctoral FellowOlga M. Antón, Postdoctoral FellowL. Michael Thomas, Postdoctoral FellowGeoffrey Hart, Postdoctoral FellowKaveh Abdi, BiologistGunjan Arora, Postdoctoral FellowMalcolm Sim, Ph.D. student, Wellcome Trust-NIH Graduate Program
The Molecular and Cellular Immunology Section has joined the newly created Malaria Research Program at NIAID—October 2015.
Anton OM, Vielkin S, Peterson ME, Tagaya Y, Long EO. NK cell proliferation induced by IL-15 transpresentation is negatively regulated by inhibitory receptors. J Immunol. 2015. In press.
Zhang M, March ME, Lane WS, Long EO. A signaling network stimulated by β2 integrin promotes the polarization of lytic granules in cytotoxic cells. Sci Signal. 2014 Oct 7;7(346):ra96.
Long EO, Kim HS, Liu D, Peterson ME, Rajagopalan S. Controlling natural killer cell responses: integration of signals for activation and inhibition. Annu Rev Immunol. 2013 Mar 21;31:227-58.
Rajagopalan S, Long EO. Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling. Proc Natl Acad Sci U S A. 2012 Dec 11;109(50):20596-601.
Liu D, Peterson ME, Long EO. The adaptor protein Crk controls activation and inhibition of natural killer cells. Immunity. 2012 Apr 20;36(4):600-11.
Kim HS, Das A, Gross CC, Bryceson YT, Long EO. Synergistic signals for natural cytotoxicity are required to overcome inhibition by c-Cbl ubiquitin ligase. Immunity. 2010 Feb 26;32(2):175-86.
Visit PubMed for a complete publication listing.Visit Google Scholar for a complete citation listing.
Research can be thrilling, but it is never easy. Do you have what it takes? We are always interested in recruiting bright and motivated young scientists. If you think this describes you, send us an application. Experience in imaging, cell biology, proteomics or bioinformatics would be a plus.
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Fellowships will be awarded annually to a limited number of top applicants who aspire to improve our understanding of the biology, host-pathogen interactions, and transmission of malaria parasites.
See Malaria Research Program.
Submit an online application at Post-baccalaureate Intramural Research Training Award (Postbac IRTA/CRTA).
Rajagopalan S, Lee EC, DuPrie ML, Long EO. TNFR-associated factor 6 and TGF-β-activated kinase 1 control signals for a senescence response by an endosomal NK cell receptor. J Immunol. 2014 Jan 15;192(2):714-21.
Martinez E, Brzostowski JA, Long EO,* Gross CC.* Cutting edge: NKG2D-dependent cytotoxicity is controlled by ligand distribution in the target cell membrane. J Immunol. 2011 May 15;186(10):5538-42. *Co-senior authors
Rajagopalan S, Moyle MW, Joosten I, Long EO. DNA-PKcs controls an endosomal signaling pathway for a proinflammatory response by natural killer cells. Science Signaling. 2010; 3:ra14
Last Updated October 29, 2015