Professor Ian M. Adcock, Professor of Respiratory Cell and Molecular Biology, NHLI, will present his Professorial Lecture: ‘Steroid Insensitivity in Asthma and COPD’.
Abstract: Most patients with asthma are well controlled by inhaled glucocorticoids (GC), however, a small proportion with severe disease fail to respond adequately to this treatment. A spectrum of GC responsiveness in airway inflammatory diseases may exist reflecting several mechanisms, secondary either to disease activity itself or to the effects of therapy, with the GC resistant asthmatic at one extreme of this spectrum. At a molecular level, resistance to the anti-inflammatory effects of GCs can be induced by several mechanisms.
Chronic obstructive pulmonary disease (COPD) is chronic inflammatory disease of the airway predominantly driven by cigarette smoke. Even high doses of inhaled or oral glucocorticoids are virtually ineffective in patients with COPD compared to the marked responses seen in most asthmatics. In COPD there is a marked increase in oxidative stress which may contribute to glucocorticoid-insensitivity. We have shown that there is reduced expression of histone deacetylase-2 (HDAC2) in COPD lung and airways. This would result in enhanced pro-inflammatory gene expression and reduced glucocorticoid responsiveness. Understanding the molecular mechanisms involved may lead to the development of an effective therapeutic strategy for COPD.
Biography: Having graduated from Bedford College with a degree in Biochemistry and Physiology I pursued a PhD in Molecular Pharmacology at St Thomas’s Hospital Medical School. This Thesis entitled “the pharmacology of oestrogen receptors in the rat limbic system and its effects on sexual behaviour” was awarded in 1987. After short spells at the MRC Brain Metabolism Unit and at St George’s Hospital to learn the “new arts” of molecular biology, I joined Peter Barnes’ group at the NHLI in 1990. I have worked for the past 15 years on the molecular pharmacology of glucocorticoid receptor function and inaction in respiratory diseases including severe asthma and COPD. We were one of the first groups to show cross-talk between NF-B and the glucocorticoid receptor and have examined how inflammatory stimuli induce gene transcription and how glucocorticoid receptor recruitment of repressor proteins is important for steroid function in disease. The work here has been very productive in terms of papers (>150) and grants (>£10m from various sources including The Medical Research Council, The Wellcome Trust, Asthma UK, The National Institutes of Health, EU Framework 6, AstraZeneca, GlaxoSmithKline, Mitsubishi Japan, Novartis, Pfizer and Sirtris).
A pre lecture tea reception will be served from 16.45 in the Refectory.