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Laboratory of Immunogenetics

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Eric O. Long, Ph. D.

Photo of Eric Long, Ph.D.

Chief, Molecular and Cellular Immunology Section, LIG

Major Areas of Research

  • Proteomics and imaging as tools to investigate signal transduction
  • Regulation through inhibitory receptors
  • Integrin signaling
  • Natural killer (NK) cell function in malaria
  • Role of NK cells in pregnancy
 

Program Description

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.

Outstanding questions

  1. How are activating and inhibitory signals integrated to control NK cell function and licensing?
  2. How does the recognition of HLA-peptide complexes by inhibitory receptors influence disease?
  3. How do integrins signal to regulate NK cell function?
  4. What signals control NK cell regulation of vascular remodeling in pregnancy?
  5. What is the role of NK cells in immunity to Plasmodium?

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Biography

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.

Research Group

Sumati Rajagopalan, Ph.D., Staff Scientist

Mary E. Peterson, Biologist
Minggang Zhang, Postdoctoral Fellow
Olga M. Antón, Postdoctoral Fellow
Santosh Kumar, Postdoctoral Fellow
L. Michael Thomas, Postdoctoral
Malcolm Sim, Ph.D. student, Wellcome Trust-NIH Graduate Program
Geoffrey Hart, Postdoctoral Fellow

photo of Long's research group
Back row (L-R): Olga Antón, Santosh Kumar, Sumi Rajagopalan, Mike Thomas, Mary Peterson, Eric Long, Minggang Zhang
Front row (L-R): postbacs Elizabeth Lee, Matt DuPrie, Zach Liao
 

News

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

Recent Alumni

Dongfang Liu (2005–2010)
Assistant Professor (2012)
Center for Human Immunobiology
Baylor College of Medicine
Houston, TX
dongfanl@bcm.edu

Yenan Bryceson (Ph.D. student 2003–2008)
Assistant Professor (2011)
Center for Infectious Medicine
Karolinska Institute
Stockholm, Sweden
yenan.bryceson@ki.se

Hun Sik Kim (postdoc 2007–2010)
Assistant Professor (2010)
Department of Microbiology
Ulsan University School of Medicine
Seoul, Korea
hunkim@amc.seoul.kr

Catharina Gross (postdoc 2005–2010)
Tenure-track Investigator (2010)
Universitätsklinikum Münster
Department of Neurology
Münster, Germany
catharina.gross@ukmuenster.de

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Selected Publications

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.

Caption and alt tag: Cover of Immunity, July 17, 2009, issue.
Cover of Immunity, July 17, 2009, issue.

How to Apply

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.

Postdoctoral fellow
Submit in PDF format (include identifier in file name)

  • Statement of interest (why you would like to work here)
  • Curriculum vitae and bibliography
  • Name and contact of three references
    Note: Do not attach letters of recommendation to your application.

Graduate student

Post-baccalaureate fellow

We are not currently accepting postbac applications.

Recent publications by postbac alumni
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

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Last Updated October 24, 2013