Exploring the Potentials of Selective Blocking of the IL-1 System by Distinct Targeting of the Co-receptor TILRR
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“Exploring the Potentials of Selective Blocking of the IL-1 System by Distinct Targeting of the Co-receptor TILRR”
Dr. Qwarnstrom’s research focuses on regulation of receptor function and cell signalling. Work on signal transduction, has centred on regulation of NF-B pathways and on using single cell recordings of regulatory events in live cells. The single cell data was used as the basis for developing highly detailed, predictive models of the IL-1 system and the NF-B network. Interdisciplinary projects led to identification and characterisation of the IL-1R1 co-receptor TILRR and established its role in IL-1 receptor function, NF-B regulation and disease. Ongoing work focuses on evaluating TILRR as a potential therapeutic target.
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Abstract
“Exploring the Potentials of Selective Blocking of the IL-1 System by Distinct Targeting of the Co-receptor TILRR”
Aberrant activation of NF-B plays a central role in disease. IL-1 is a key regulator of NF-B and has emerged as a rational therapeutic target. Clinical trials have demonstrated that nonselective blocking of the IL-1 system can cause serious side effects related to impairment of the immune system, highlighting the need for more specific targeting. Our interdisciplinary studies on regulation of NF-B led to identification of the IL1R1 coreceptor TILRR and established its role in controlling IL1R1 function and in driving aberrant activation of NF-B. Our published work shows that genetic deletion or antibody blocking of TILRR reduces progression of inflammatory conditions. Pathway enrichment analysis of TILRR-induced gene expression profiles has revealed significant links with NF-B signalling, Alzheimer’s disease and cancer. I will describe the predictive modelling approaches used in these studies, outline the key regulatory events that underpin TILRR’s control of the IL-1 system and selective regulation the NF-B pathways, present recent data on the role of TILRR in disease and discuss its potential as a therapeutic target.
