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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.Pestal K, Funk CC, Snyder JM, Treuting PM, Price ND, Stetson DB. 2015. Isoforms of the ADAR1 RNA editing enzyme independently control nucleic acid sensor MDA5-driven autoimmunity and multi-organ development. Immunity, in press.
2.Lau L, Gray EE, Brunette RL, Stetson DB. 2015. DNA tumor virus oncogenes antagonize the cGAS-STING DNA sensing pathway. Science, 350(6260):568-571.
3.Gray EE, Treuting PM, Woodward JJ, Stetson DB. 2015. cGAS is required for lethal autoimmune disease in the Trex1-deficient mouse model of Aicardi-Goutieres Syndrome. Journal of Immunology, 195(5):1939-1943.
4.Eckard SC, Rice GI, Fabre A, Badens C, Gray EE, Hartley JL, Crow YJ, Stetson DB. 2014. The SKIV2L RNA exosome limits activation of the RIG-I-like receptors. Nature Immunology, 15(9):839-845. NIHMS ID: 609228.
5.Volkman HE, Stetson DB. 2014. The enemy within: endogenous retroelements and autoimmune disease. Nature Immunology, 15(5):415-422. NIHMS ID: 608398.
6.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):1969-1983. PMCID: PMC3478938.
7.Gall A, Treuting P, Elkon KB, Loo Y-M, Gale M Jr, Barber GN, Stetson DB. 2012. Autoimmunity initiates in non-hematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease. Immunity, 36(1):120-131. PMCID: PMC3269499.
B.S., Biology, Duke University
Ph.D., Biomedical Sciences, University of California, San Francisco