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Daniel B. Stetson, Ph.D.
Daniel B. Stetson, Ph.D.
Associate Professor, Immunology
Dan Stetson graduated from Duke University in 1997 and received his PhD in 2002 from the University of California, San Francisco. After completing postdoctoral work at Yale University, Dr. Stetson joined the University of Washington Department of Immunology in April 2008.
Department of Immunology
University of Washington
Office E453, Box 3578059
750 Republican Street
Seattle WA 98109-8059
Research in the Stetson lab focuses on mechanisms by which cells detect and respond to viral infection. All organisms have viral pathogens, and an ancient and fundamental mechanism for detecting viral infection makes use of sensors that recognize viral nucleic acids. In vertebrates, these sensors coordinate an inducible antiviral response by activating the production of type I interferons (IFNs). While the pleiotropic roles of IFNs have been studied since their discovery over five decades ago, recent advances have allowed us to understand their means of induction and complex regulation at a molecular level.
We are particularly interested in a recently described pathway that detects cytosolic DNA within mammalian cells. This pathway, termed the interferon stimulatory DNA (ISD) response, is analogous to the well-characterized RIG-I and MDA5 RNA helicases that detect RNA. However, the ISD pathway signals activation of the antiviral response through a distinct, still poorly characterized mechanism. One goal of our research is to define the specific signaling cascades of the ISD pathway and, more importantly, to determine why they are different from those activated by viral RNA. Another is to understand the biological relevance of the ISD pathway and its connections to Toll-like receptor mediated nucleic acid detection.
Nucleic acid recognition is the principal strategy of viral detection, yet its very nature raises fundamental questions of self/non-self discrimination because of the abundance of self-derived nucleic acids in all cells. We are developing novel mouse model systems to study how dysregulated nucleic acid detection initiates and precipitates autoimmunity and investigating a new mechanism of autoimmunity caused by excessive activation of cytosolic nucleic acid sensors. Finally, the recent renaissance in our understanding of nucleic acid detection will allow us to revisit a number of long-standing, unanswered questions. One fascinating example is the question of why DNA viruses – but not RNA viruses – cause cancer. This question can now be framed in specific molecular terms, and tools are being developed to probe the interconnections between DNA-activated antiviral responses and tumor suppression.
1. Stetson DB. 2012. Endogenous retroelements and autoimmune disease. Current Opinion in Immunology, 24(6):692-697.
2. Brunette RL, Young JA, Whitley DG, Brodsky IE, Malik HS, Stetson DB. 2012. Extensive evolutionary and functional diversity among mammalian AIM2-like receptors. Journal of Experimental Medicine, 209(11):1969-1883. PMCID: PM3478938.
3. Gall A., Treuting P., Elkon KB, Loo YM, Gale M Jr., Barber GN, Stetson, DB. Autoimmunity Initiates in Nonhematopoietic Cells and Progresses via Lymphocytes in an Interferon-Dependent Autoimmune Disease. Immunity. 2012 Jan 27; 36(1):120-31. PMID 22284419.
4. Stetson DB. 2009. Connections between antiviral defense and autoimmunity. Current Opinion in Immunology 21(3):244-250.
5. Rice GI, Bond J, Asipu A, Brunette RL, Manfield IW, Carr IM, Lamb T, Briggs TA, Ali M, Couthard LR, Aeby A, Attard-Montalto S, Bertini E, Bodemer C, Brockmann K, Brueton LA, Corry PC, Desguerre I, Fazzi E, Fuller J, Garcia Cazorla A, Gener B, Hamel BCJ, Heiberg A, Hunter M, Jackson R, van der Knaap M, Kumar R, Lagae L, Landrieu PG, Lourenco CM, Marom D, McDermott M, van der Merwe W, Orcesi S, Prendiville J, Rasmussen M, Shalev SA, Soler D, Shinawi M, Spiegel R, Tan T, Vanderver A, Wakeling E, Wassmer E, Whittaker E, Lebon P, Stetson DB, Bonthron DT, Crow YJ. 2009. Mutations in Aicardi-Goutières syndrome implicate SAMHD1 as a novel regulator of the innate immune response. Nature Genetics 41(7):829-832
6. Stetson DB*, Ko JS, Heidmann T, Medzhitov R*. 2008 Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 134:587-598. *Corresponding authors PMCID: PMC2626626
7. Stetson DB adn Medzhitov R. 2006 Recognition of cytosolic DNA activates in IRF3-dependent innate immune response. Immunity 24(1):93-103
B.S., Biology, Duke University
Ph.D., Biomedical Sciences, University of California, San Francisco