Daniel B. Stetson, Ph D
Assistant Professor, Immunology

Department of Immunology
University of Washington
Office: I-607I, HSC
1959 NE Pacific Street, 357650
Seattle, WA 98195-7650
Tel: 206-543-6633
Fax: 543-1013
Email: stetson@u.washington.edu

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.

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.

Recent Publications:

Stetson DB and Medzhitov R. 2006. Type I interferons in host defense. Immunity 25(3); 373-381.

Stetson DB and Medzhitov R. 2006. Antiviral defense: interferons and beyond. Journal of Experimental Medicine 203(8):1837-1841.

Stetson DB and Medzhitov R. 2006. Recognition of cytosolic DNA activates an IRF3-dependent innate immune response. Immunity 24(1):93-103.

Scheu S, Stetson DB, Reinhardt RL, Leber JH, Mohrs M, Locksley RM. 2006. Activation of the integrated stress response during helper T cell differentiation. Nature Immunology 7(6):644-651.

Stetson DB, Voehringer D, Grogan JL, Xu M, Reinhardt RL, Scheu S, Kelly BL, Locksley RM. 2004. Th2 cells: orchestrating barrier immunity. Advances in Immunology 83:163-189.

Stetson DB, Mohrs M, Reinhardt RL, Baron JL, Wang Z-E, Gapin L, Kronenberg M, Locksley RM. 2003. Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. Journal of Experimental Medicine 198(7):1069-1076.

Posted 12-14-07