Molecular Cell Biology

Professor Ian Adcock, Head of Group and Dr Kazuhiro Ito 

The overarching theme of the research in this group is the investigation of the molecular mechanisms underlying chronic inflammation in asthma and COPD. The mechanisms by which glucocorticoids regulate this enhanced inflammation is also under active investigation. These studies are performed in both cultured and primary epithelial cells, T-cells and monocytes/macrophages and in human lung tissues.  As a group we use standard molecular, pharmacological and histological techniques including reporter gene assays, mutagenesis, overexpression, Western blotting, RT-qPCR, confocal imaging, chromatin immunoprecipitation and siRNA. There is a major focus on translational research with the application of state-of-the-art molecular techniques to primary cells from patients with airways disease.  Due to the translational nature of our research we have extensive collaborations with clinical colleagues (Barnes, Chung, Haskard, Johnston, Kon, Marczin, Russell, Usmani & Wort) and with animal model groups (Belvisi & Chung) within Imperial.  The ultimate goal of the group is to determine why steroids are ineffective in suppressing the inflammatory response seen in severe asthma and COPD.

Using this approach we research the following areas:

• to explore cross-talk between GR and other transcription factors in the regulation of immunomodulatory genes in T-cells, macrophages and epithelial cells.
• to investigate the role of chromatin modifications and remodeling on GR function.
• to examine the role of specific transcriptional co-activators and co-repressors on GR function and whether they are defective in severe disease.
• to determine the role of post-translational modifications of GR on co-factor recruitment and nuclear translocation.
• to perform functional genomics on genes associated with severe asthma phenotype in collaboration with Professors Cookson and Moffat
• to determine the effect of acute and chronic rhinoviral infection on inflammation and steroid responsiveness in primary airway epithelial cells
• Determine the ability of oxidative and carbonyl stress to modify inflammatory gene expression and its repression by steroids.
• Examine the effect of oxidative/carbonyl stress on post-translational modifications of key transcription factors/co-repressor proteins.
• Elucidate the effect of carbonyl modification of self proteins on auto-immunity in COPD and in disease models.

Selected Publications

Maneechotesuwan K; Yao X; Ito K; Jazrawi E; Usmani OS; Adcock IM; Barnes PJ. (12 May 2009). Suppression of GATA-3 nuclear import and phosphorylation: a novel mechanism of corticosteroid action in allergic disease. PLoS Med. 6:e1000076.

Ito K; Yamamura S; Essilfie-Quaye S; Cosio B; Ito M; Barnes PJ; Adcock IM. (23 Jan 2006). Histone deacetylase 2-mediated deacetylation of the glucocorticoid receptor enables NF-kappaB suppression. J Exp Med. 203:7-13.

Ito K; Ito M; Elliott WM; Cosio B; Caramori G; Kon OM; Barczyk A; Hayashi S; et al. (12 May 2005). Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med. 352:1967-1976.