Eric O. Long, Ph.D.
Fetal protein reprograms immune cells to aid pregnancy success.
Chief, Molecular and Cellular Immunology Section, LIG
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 the Malaria Infection Biology and Immunity Unit and the Lymphocyte Activation Section, we are 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.
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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 antigen 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 FellowSantosh Kumar, Postdoctoral FellowL. Michael Thomas, PostdoctoralMalcolm Sim, Ph.D. student, Wellcome Trust-NIH Graduate ProgramGeoffrey Hart, Postdoctoral Fellow
The Twinbrook seminar series schedule for 2013 to 2014 is now available—October 2013 – June 2014
An MCIS paper has been selected as one of the Pillars of Immunology by the Journal of Immunology—October 2013
The 14th meeting of the Society for Natural Immunity (NK2013) took place in Heidelberg, Germany— September 18 – 22, 2013
A symposium on Receptors and Cytokines in Innate Immunity was held at NIH on April 2–3, 2013—April 2013
A feature on MCIS research was posted to the NIAID website: Protein Secreted by the Fetus During Pregnancy May Reprogram Immune Cells—December 2012
Dongfang Liu (postdoc, 2005–2010-) is now assistant professor at Baylor College of Medicine—July 2012
Eric Long has received the NIH Director’s Award—July 2012
Minggang Zhang has won an NIH Fellows Award for Research Excellence—June 2012
Dongfang Liu (2005–2010)Assistant Professor (2012)Center for Human ImmunobiologyBaylor College of MedicineHouston, TXdongfanl@bcm.edu
Yenan Bryceson (Ph.D. student 2003–2008)Assistant Professor (2011)Center for Infectious MedicineKarolinska InstituteStockholm, Swedenyenan.firstname.lastname@example.org
Hun Sik Kim (postdoc 2007–2010)Assistant Professor (2010)Department of MicrobiologyUlsan University School of MedicineSeoul, Koreahunkim@amc.seoul.kr
Catharina Gross (postdoc 2005–2010)Tenure-track Investigator (2010)Universitätsklinikum MünsterDepartment of NeurologyMünster, Germanycatharina.email@example.com
Long EO, Sik Kim H, 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.
Kim HS, Long EO. Complementary phosphorylation sites in the adaptor protein SLP-76 promote synergistic activation of natural killer cells. Sci Signal. 2012 Jul 10;5(232):ra49.
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.
Liu D, Bryceson YT, Meckel T, Vasiliver-Shamis G, Dustin ML, Long EO. Integrin-dependent organization and bidirectional vesicular traffic at cytotoxic immune synapses. Immunity. 2009 Jul 17;31(1):99-109.
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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We are not currently accepting postbac applications.
Recent publications by postbac alumniMartinez 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 24, 2013