Research Fellows Directory
Dr Paul Kirkham
Novartis Horsham Research Centre
Chronic obstructive pulomonary disease (COPD) affects up to 10% of the global population and is set to become the third highest cause of death worldwide. It is a progressive non-reversible disease characterized by chronic airflow obstruction of the small airways, mucus hypersecretion, destruction of the lung tissue (emphysema) and chronic inflammation. Existing treatments do not work, representing a clear unmet medical need. Over 3 million people within the UK are currently affected costing over £1 billion/year in direct healthcare costs, which are set to rise with increasing disease prevalence and an aging population. The implications of this disease to society are therefore enormous and new treatments are urgently needed. These can only come about by understanding how the damage to the lungs is caused in COPD. Cigarette smoking and continued exposure to airborne pollution are sources of oxidants that can overwhelm your own anti-oxidant defences and leads to oxidative stress in the lung, the major cause of COPD. Oxidative stress causes damage to the cells and tissues within the lungs due to modification of proteins that make up each cell. These modified proteins, referred to as carbonyl-modified proteins, accumulate over time and lead to increased levels in COPD patients and increase further as the disease worsens. Carbonyl-modified proteins are very potent stimulants of the immune system. The aim of this fellowship was to prove whether these carbonyl-modified proteins produced during the disease process can trigger the body’s own immune system into attacking itself by producing autoantibodies and activated immune cells against these carbonyl-modifed ‘self’ proteins, a process known as autoimmunity and believed to be one of the mechanisms responsible for the lung destruction seen in COPD. The results obtained proved that this was indeed the case and moreover the disease could be replicated in an in vivo model, an important step in testing future therapeutic drugs.