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Research in our laboratory focuses on the regulation of the innate immune response to pathogens with an emphasis on macrophages and dendritic cells. Macrophages and dendritic cells are distributed throughout the body where they are poised to detect pathogens and to subsequently alert the immune system to the presence of infection through the production of inflammatory mediators. The production of inflammatory mediators, such as tumor necrosis factor (TNF) and other pro-inflammatory cytokines, is tightly regulated. Although these important cytokines are beneficial to the host for pathogen clearance, they can be detrimental if unchecked. This can be seen in both acute settings, such as infection, as well as in the chronic setting of autoimmune diseases.
Macrophages and dendritic cells recognize pathogens by a variety of cell surface and intracellular receptors termed pattern recognition receptors, including the family of Toll-like receptors (TLR). We study how signaling through pattern recognition receptors results in the appropriate inflammatory response by macrophages and dendritic cells. We are particularly interested in proteins that inhibit signaling through pattern recognition receptors, providing an essential check to the inflammatory response. We study several proteins that inhibit TLR signaling, including TREM-2, DAP12 and BCAP, through biochemical approaches and in vivo infectious models.
We also have a new interest in the development of cells that participate in innate immune responses, such as macrophages, neutrophils and dendritic cells. This process of myelopoiesis occurs in the bone marrow and can respond dynamically to infection and inflammation to produce more cells when needed, such as during infection. We are studying how myeloid progenitors in the bone marrow increase and modify their output during infection and inflammation, with a focus on type I interferon family of cytokines. Type I interferons are produced during viral infections and certain autoimmune diseases, such as SLE, and we are focusing on understanding this novel role of these cytokines in driving myelopoiesis.
Copyright © 2003-2014 Molecular & Cellular Biology Program, University of Washington
Fred Hutch | University of Washington
Institute for Systems Biology (ISB)| Center for Infectious Disease Research