Dr. Harrington graduated from Purdue University in 1978 with a BS in Nutritional Sciences; in 1980, she received an MS in Population Studies from the University of Texas School of Public Health working on pesticide resistance in mosquitos. In 1985 she received her PhD in Pharmacology from The University of North Carolina-Chapel Hill for work performed with Dr. Jack Pledger on the control mammalian cell growth and division. From 1985 through 1987, she was a post-doctoral fellow in the Norris Comprehensive Cancer Center at the University of Southern California where she worked with Dr. Peter Jones, beginning her long-standing interest signal specific control of gene expression. Following a brief post-doctoral fellowship in molecular hematopoiesis in Dr. Hal Broxmeyer’s laboratory (IUSM), Dr. Harrington joined the faculty at the Indiana University School of Medicine. Her research interests have focused on elucidating cellular and molecular mechanisms used to achieve specificity in growth factor/cytokine-specific changes in gene expression. Initial efforts in the lab focused on interleukin-1 (IL-1) signaling using basic cell biology and genetic approaches. Downstream of the Drosophila Toll receptor, which shares homology with the type I IL-1 receptor, is pelle, a serine/threonine kinase. Dr. Harrington with her collaborator, Dr. Goebl were the first to clone the mouse homolog of pelle [mouse pelle-like kinase, (mPLK)], the mouse homolog of the IL-1 receptor associated kinase (IRAK-1). Excitingly further study revealed that mPLK/IRAK-1 kinase activity was required for full TNFα induced NF-κB activity and was not required for IL-1 induced NF-kB activity. Thus her lab has continued to focus on determining the functional significance of mPLK/IRAK-1 in the context of TNFα signaling. They next identified SIMPL, a mPLK/IRAK-1 binding protein/substrate. To assess the biological significance of SIMPL, the SIMPL-/- mice were generated. Analysis of mouse embryo fibroblasts derived from SIMPL-/- and littermate control mice reveal that SIMPL controls a subset of TNFα induced NF-κB dependent genes, including TNFα itself, that are linked to the inflammatory response. Analysis of the hematopoietic compartment in SIMPL-/- mice revealed fewer stem cells, a phenotype also seen in TNFα-/- mice. Further characterization of SIMPL has revealed that it functions in a TNFα-TNF RI specific manner to specifically enhance the trans-activation activity of the Rel family member, p65. Studies underway in the laboratory are focused on determining the molecular mechanism through which SIMPL mediates the synergistic enhancement of p65 activity.