My research concerns the identification and mapping of signaling pathways involved in inflammation. Currently, we are investigating the mechanism of activation of TAK1, a mitogen activated protein kinase kinase kinase (MAPKKK). TAK1 is activated by pro-inflammatory cytokines such as interleukin-1 (IL-1) and tumour necrosis factor-α (TNF-α), and also by bacterial lipopolysaccharides (LPS). Engagement of these three stimuli with their receptors leads to the activation of the inflammatory response via the JNK, p38α and NFκB pathways which all lie downstream of TAK1. However, dysregulation of these pathways can lead to chronic inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, psoriasis and asthma. As TAK1 is a key component in transducing inflammatory signals, inhibition of TAK1 by therapeutic means may be attractive as treatment for these diseases
