Alan A. Aderem, Ph.D.
ADJUNCT PROFESSOR, IMMUNOLOGY AND PROFESSOR OF MEDICINE; CO-FOUNDER, INSTITUTE FOR SYSTEMS BIOLOGY
Dr. Aderem received his Ph.D. in 1979 from the University of Cape Town, South Africa, and joined the faculty of the Rockefeller University, New York, in 1982. In 1991 he was appointed head of the Laboratory of Signal Transduction at the Rockefeller University. He joined the Department of Immunology at the University of Washington in 1996. In 2000, Dr. Aderem co-founded the Institute for Systems Biology (ISB) with Drs. Leroy Hood and Ruedi Aebersold. In 2011, Aderem joined the Center for Infectious Disease Research (CID Research) as director, and he will become the CID Research president in 2012. Working alongside CID Research’s Founder and current President Dr. Ken Stuart, Dr. Aderem is integrating a systems biology approach to CID Research’s global infectious disease research, positioning the Center as the only institute in the world with infectious disease research and systems biology fully integrated in one building.
CONTACT INFOalan.aderem@seattlechildrens.org Phone: 206-256-7333
Fax: 206-256-7229
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RESEARCH AREASAdaptive Immune Responses LAB MEMBERSAlan Diercks, Senior Scientist – alan.diercks@seattlechildrens.org Graduate Students Rudy Nazitto, rnazitto@uw.edu
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LABACCEPTING NEW STUDENTS: NO Aderem Lab at Seattle Children’s PUBMED |
RESEARCH
Research projects
Systems Approach to Immunity and Inflammation
Systems approaches combine what we already know (prior biological knowledge) with the analysis of massive amounts of new data (collected through global measurement technologies and computational methods). Merging these levels of information can reveal novel regulatory interactions between molecules and places them in context within the immune system. Identifying regulatory nodes in immune cells that control specific sub-networks of the innate response is critical to the development of therapeutic strategies that aim to either harness specific immune functions, such as for vaccine adjuvants, or to mitigate inflammation-driven diseases such as atherosclerosis and lupus. Two key cell types in the innate immune system are macrophages and dendritic cells, which display an arsenal of receptors for detecting pathogens and play critical roles in pathogen clearance, cytokine production, and the initiation of adaptive immunity. Systems biology studies of macrophages and dendritic cells in the Aderem Lab have generated testable hypotheses for the role of a large number of molecules in innate immune responses. We are testing how mutating these molecules or perturbing their networks will impact immune responses against tuberculosis, HIV, influenza, and other pathogens. To learn more, please visit www.SystemsImmunity.org.
Omics for TB Disease Progression (OTB)
Roughly one third of the world’s population is latently infected with Mycobacterium tuberculosis. Over their lifetimes, many of these individuals (with no outward signs of illness) will transition to active disease. We have no biological understanding of what drives this conversion from latent to active disease states. The overall goal of this project is to apply omics technologies and systems-based modeling to define the key bacterial and host determinants of the progression from latent infection to active disease. This work involves collaborations with several groups at the Center for Infectious Disease Research, including the Zak, Sherman, and Urdahl Labs, as well as the Baliga Lab at the Institute for Systems Biology (www.omics4tb.org).
Exploring Innate Immune Signaling
The innate immune system detects pathogens and pathogen components such as lipopolysaccharide (LPS) via pattern recognition receptors. These include the Toll-like receptors (TLRs), the Nod-like receptors (NLRs), the Rig-I-like receptors (RLRs), cytoplasmic DNA receptors (cGAS), and others. Some of these receptors trigger anti-viral responses by inducing type I interferons (type I IFNs). This induction must be tightly regulated since over-exuberant production of IFN can contribute to autoimmunity. The transcription factor IRF7 is a “master regulator” of systemic type I IFN responses. While much is known about the activation of IRF7, the mechanisms by which it is regulated and de-activated remain poorly explored. We have recently identified a regulatory circuit involving IRF7 and another transcription factor, FOXO3, whereby excessive IFN responses are kept in check by FOXO3-mediated repression of IRF7-dependent genes (Litvak et al., Nature 2012). We are currently extending these studies to explore the regulation of other signaling networks that are engaged downstream of TLRs, RLRs, and other receptors. This is an exciting area of research that underscores the importance of genetic and epigenetic regulation of interferon and illuminates new concepts in innate immunity.
PUBLICATIONS
- Gold ES, Ramsey SA, Sartain MJ, Selinummi J, Podolsky I, Rodriguez DJ, Moritz RL, Aderem A. 2012. ATF3 protects against atherosclerosis by suppressing 25-hydroxycholesterol-induced lipid body formation. J. Exp. Med. 209: 807-17. PMCID: 3328364
- Negishi H, Yanai H, Nakajima A, Koshiba R, Atarashi K, Matsuda A, Matsuki K, Miki S, Doi T,Aderem A et al. 2012. Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Nat Immunol. 13(7): 659-66.
- Sissons JR, Peschon JJ, Schmitz F, Suen R, Gilchrist M, Aderem A. 2012. Cutting edge: MicroRNA regulation of macrophage fusion into multinucleated giant cells. J Immunol. 189: 23-7.PMCID:3381877.
- Litvak V, Ratushny AV, Lampano AE, Schmitz F, Huang AC, Raman A, Rust AG, Bergthaler A, Aitchison DJ, Aderem A. 2012.A FOXO3-IRF7 gene regulatory circuit limits inflammatory sequelae of antiviral responses. Nature. 490:421-5. PMCID: 3556990
- Nakayama M, Kurokawa K, Nakamura K, Lee BL, Sekimizu K, Kubagawa H, Hiramatsu K, Yagita H, Okumura K, Takai T, Underhill DM, Aderem A, Ogasawara K. 2012. Inhibitory receptor paired IG-like receptor B is exploited by Staphylococcus aureus for virulence. J Immunol. 189: 5903-11.
- Zak DE, Andersen-Nissen E, Peterson ER, Sato A, Hamilton MK, Borgerding J, Krishnamurty AT, Chang JT, Adams DJ, Hensley TR, Salter AI, Morgan CA, Duerr AC, De Rosa SC, Aderem A, McElrath MJ. 2012. Merck Ad5/HIV induces broad innate immune activation that predicts CD8+ T-cell responses but is attenuated by preexisting Ad5 immunity. Proc Natl Acad Sci USA. 109: E3503-12. PMCID: 3528489
- Rosenberger CM, Podyminogin RL, Navarro G, Zhao GW, Askovich PS, Weiss MJ, Aderem A. 2012. miR-451 regulated dendritic cell cytokine responses to influenza infection. J Immunol.189:5965-75. PMCID: 3528339
- Aachoui Y, Leaf IA, Hagar JA, Fontana MF, Campos CG, Zak DE, Tan MH, Cotter PA, Vance RE,Aderem A, Miao EA. 2013. Caspase-11 protects against bacteria that escape the vacuole. Science.339:975-8. PMCID: 3697099
- Tam VC, Quehenberger O, Oshansky CM, Suen R, Armando AM, Treuting PM, Thomas PG, Dennis EA, Aderem A. 2013. Lipidomic profiling of influenza infection identifies mediators that induce and resolve inflammation. Cell. 154:213-27. PMCID: In process.
- Zak DE, Aderem A. 2012. Overcoming limitations in the systems vaccinology approach: A pathway for accelerated HIV vaccine development. Curr Opin HIV AIDS. 7: 58-63.
- Aderem A, Czerkinsky C. 2012 June 12. Editorial overview. Curr Opin Immunol. [Epub ahead of print]
- Diercks A, Aderem A. 2012 August 11. Systems approaches to dissecting immunity. Curr Top Microbiol Immunol. [Epub ahead of print]
