Structural basis for the pathogenic disease mechanisms caused by chronic inflammation

Research Project Outline

Chronic inflammation results from excessive physiological responses, which are intrinsically essential for maintaining normal life, or by disturbances of physiological responses triggered by viral and bacterial infections. Chronic inflammation can cause adult-onset diseases, such as cancers, diabetes, arterial sclerosis, and others. We primarily focus on the following three areas:
1. Lipid mediators and the enzymes that produce them, which cause chronic inflammation via GPCR;
2. Toll-like receptors (TLRs) and signal transducers involved in natural inflammation downstream of TLR activation;
3. Transcriptional regulators that control cellular signaling in the nucleus, particularly NF-κ B.
We determine the three-dimensional structures of the target proteins and their complexes by X-ray crystallography, and provide evidence for the working hypothesis by mutant analyses, that identifies the mechanisms of chronic inflammation causing various diseases, from atomic to individual levels.