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Iain Fraser, Ph.D.
Building 4, Room 109A
4 Memorial Drive
Bethesda, MD 20892-0485
Phone: 301-443-5998
Fax: 301-480-5725
fraseri@niaid.nih.gov

Laboratory of Systems Biology

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Iain D.C. Fraser, Ph.D.

Photo of Iain D.C. Fraser, Ph.D.

Chief, Signaling Systems Unit, LSB
Tenure-Track Investigator

Major Areas of Research

  • Analysis of the signaling pathway interactions in immune cells that define context-specific responses to pathogens
  • Profiling and modeling of the cellular response to complex stimuli
  • Application of RNAi screening technology to the identification of signaling network components in immune cells
  • Design and implementation of high-throughput and high-content assays to facilitate computational modeling of immune cell behavior and function
 

Program Description

The Signaling Systems Unit is focused on the design, implementation, and interpretation of screening efforts to identify and determine the interactions among the components in immune cell signaling networks. We seek to determine the signal integration mechanisms that dictate the response of immune cells to combined pathogenic stimuli in a complex environment.

Recent studies of how macrophages respond to combinations of stimuli suggest that signaling networks are not irreducibly complex and that there is an infrastructure in place that dictates the frequency of signaling pathway interaction. However, cellular responses are not predictable from knowledge of single stimulus response profiles, and there is a pressing need in the biomedical research community to adopt more quantitative computational approaches to gain insight into complex biological phenomena.

 
High-content screening assay: Nuclear accumulation of NFkB (RelA) in macrophage cells treated with LPS
High-content screening assay: Nuclear accumulation of NFkB (RelA) in macrophage cells treated with LPS. Credit: NIAID
 

We use high-throughput genetic screening to identify key cellular network components and a combination of cell biology, biochemistry, and molecular biology to characterize their function. In collaboration with other LSB groups, we seek to use complementary datasets to develop models describing the cellular response to complex stimuli and to gain insight to emergent cellular behaviors that are not predictable from knowledge of single-input responses.

Ongoing projects in the lab include the following:

  • Genome-wide RNAi and chemical screens to characterize signaling network topology in hematopoietic cells and to identify the "parts list" of cellular components involved in immune cell responses
  • Development of multiplex cell-based assays for screening applications and parameterization of computational models
    • Assays focus on post-translational modification of signaling proteins, cellular re-localization of pathway components, and transcriptional responses to pathogenic stimuli.
  • Use of the above methods to characterize the response of immune cells to increasingly complex stimuli, such as single and combined pathogenic ligands, and intact pathogens, such as bacteria and viruses

Postdoctoral Opportunities

To inquire about current openings in the lab, email fraseri@niaid.nih.gov.

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Biography

Dr. Fraser received his B.S. in biochemistry from Heriot-Watt University, Edinburgh, Scotland, in 1990 and his Ph.D. in biochemistry from Imperial College, University of London, in 1995. He was a Wellcome Trust International postdoctoral fellow at the Vollum Institute in Portland, Oregon, from 1996 to 1999. He joined the Alliance for Cellular Signaling (AfCS) research consortium in 2000 as lead scientist of the molecular biology group at the California Institute of Technology and became co-director of the AfCS Molecular Biology Laboratory in 2005. He joined NIAID in 2008 as leader of the PSIIM Molecular and Cell Biology Team, which became the LSB Signaling Systems Unit in 2011.

His research has focused on the mechanistic basis of cellular signaling, both in G protein signaling networks and more recently in Toll-like receptor signaling in innate immune cells. He is interested in the application of systems biology approaches to decipher how mammalian cells integrate stimuli in a complex environment to ensure context-dependent cellular responses. This is vital to understanding how a breakdown in information processing through cell-surface receptors and their linked signal transduction pathways leads to human disease. Dr. Fraser has developed sophisticated approaches for RNAi-based perturbation analysis of immune cell signaling, as well as cloning platforms and plasmid repositories for high-throughput imaging and cell biological applications.

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Selected Publications

Sung MH, Li N, Lao Q, Gottschalk RA, Hager GL, Fraser ID. Switching of the relative dominance between feedback mechanisms in lipopolysaccharide-induced NF-κB signaling. Sci Signal. 2014 Jan 14;7(308):ra6.

Al-Khodor S, Marshall-Batty K, Nair V, Ding L, Greenberg DE, Fraser ID. Burkholderia cenocepacia J2315 escapes to the cytosol and actively subverts autophagy in human macrophages.Cell Microbiol. 2013 Oct 11. Epub ahead of print.

Germain RN, Meier-Schellersheim M, Nita-Lazar A, Fraser ID. Systems biology in immunology: a computational modeling perspective. Annu Rev Immunol. 2011 Apr 23;29:527-85.

Wall EA, Zavzavadjian JR, Chang MS, Randhawa B, Zhu X, Hsueh RC, Liu J, Driver A, Bao XR, Sternweis PC, Simon MI, Fraser ID. Suppression of LPS-induced TNF-alpha production in macrophages by cAMP is mediated by PKA-AKAP95-p105. Sci Signal. 2009 Jun 16;2(75):ra28.

Fraser ID, Germain RN. Navigating the network: signaling cross-talk in hematopoietic cells. Nat Immunol. 2009 Apr;10(4):327-31.

Shin KJ, Wall EA, Zavzavadjian JR, Santat LA, Liu J, Hwang JI, Rebres R, Roach T, Seaman W, Simon MI, Fraser ID. A single lentiviral vector platform for microRNA-based conditional RNA interference and coordinated transgene expression. Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13759-64.

View complete listing in PubMed.

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Last Updated October 19, 2012

Last Reviewed October 19, 2012