MRC Centre for Inflammation Research
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Dr Rodger Duffin

Rodger Duffin's research interests are focused on the mechanisms controlling inflammatory processes from initiation to resolution and also understanding the potential toxicology surrounding environmental and occupational nanoparticle exposures.

Dr Rodger Duffin

MRC Senior Lecturer in Respiratory Medicine

  • MRC Centre for Inflammation Research
  • Research Theme: Immune Modulation and Regulation of Inflammation

Contact details

Group Members

  • Adriano Rossi – main collaborator and co-applicant
  • Jen Raftis – Postdoctoral Research Fellow
  • Simon Wilson – Clinical Research Fellow
  • Calum Robb – Postdoctoral Research Fellow
  • Jennifer Felton – Postdoctoral Research Fellow (email)
  • Ian Smith – Research Technician
  • Craig Poland - Senior Scientist

Background

My research background covers two distinct themes both linked via the processes involved in inflammation and repair. Firstly, we aim to gain a better understanding of the mechanisms controlling inflammatory processes with a view to help develop novel therapies for chronic inflammatory diseases. For this we aim to elucidate the mechanism regulating inflammatory cell behaviour and apoptosis and manipulate the processes controlling the resolution of inflammation in order to develop new therapeutic strategies to remove unwanted and dysregulated inflammation.

Although neutrophilic and eosinophilic granulocytes are key effector cells in host defence against invading bacteria and parasites, over-recruitment, uncontrolled activation and defective removal by macrophages of these cells plays a prominent role in the initiation and propagation of chronic inflammatory conditions, including emphysema, bronchitis, rheumatoid arthritis, inflammatory bowel disease, asthma, etc.  Apoptosis or programmed cell death is a fundamental process regulating inflammatory cell survival providing an efficient non-inflammatory mechanism for removal of potentially histotoxic cells from inflamed sites by resident or recruited macrophages and is critically involved in the successful resolution of inflammation. 

Secondly, the inhalation of particles is known to be associated with the development of disease. Historically occupational exposure to coalmine dust, quartz and asbestos produced the greatest amount of ill-health in terms of pulmonary fibrosis and lung/pleural cancer.  More recently environmental particles (PM10) have been found to worsen cardiovascular disease and airways disease in individuals who are in these susceptible groups. Research focused attention on the combustion-derived nanoparticles, such as diesel exhaust, as one of the most harmful components of the PM10 particle mix. The rise of the nanotechnologies and the production of novel nanoparticles has raised concern that new hazards are being produced which need to be better understood in toxicological terms.  A better understanding of the hazard of any particle and determination of the true biologically effective dose offers the prospect of an improved metric for risk management, a target for structure-activity modelling and the prospect of rational intervention in disease progression following exposure.

Research Overview

Inflammatory diseases and especially inflammatory lung diseases, like chronic bronchitis and emphysema (COPD) and scarring conditions, are responsible for a huge burden of illness and untimely deaths in the UK, but current treatments are at best poorly-effective. Over the past 20 years we have been taking an alternative approach to harness the mechanisms by which some inflammatory responses are known to get better spontaneously. Specifically, we have identified a mechanism by which key inflammatory cells called neutrophils can be made to 'commit suicide' and be removed silently by local scavenger cells called macrophages. Unfortunately, this suicide process is usually overcome by powerful survival factors present in the inflamed lung. In work newly-published in the leading international medical science journal 'Nature Medicine' we have shown that several CDK inhibitor drugs, currently under clinical trial in cancer patients, causes an unexpected induction of neutrophil suicide, even in the presence of survival factors, and makes relevant models of human inflammatory lung disease resolve. This work has recently been publicised in the lay press. A part of our proposed programme of research we will define exactly how these CDKi drugs work, an approach which may lead to the discovery of other useful anti-inflammatory drugs.

My research also addresses the pro-inflammatory effects of particles. I have studied all of the main pathogenic particles - coalmine dust, quartz, asbestos, vitreous fibres, PM10 and manufactured nanoparticles. The characteristics of particles that lead from deposition of particles in the lungs to inflammation can be more explicitly stated in toxicological terms as the biologically effective dose (BED) for the response of inflammation. The BED varies between particle types and a large part of my research has been aimed at determining the BED because knowledge of that entity is so useful. We have especially focused on fibres, nanofibres and metal oxides and found a range of different BEDs from fibre length to charge. I am also very interested in the link between particle exposure in the lungs and adverse effects on the cardiovascular system. The latter work has been concentrated in Programme Grants from the British Heart Foundation co-led by Professor David Newby and involving Professor Nick Mills and collaborators in the Netherlands (Professor Flemming Cassee) and Sweden (Professors Thomas Sandstrom and Anders Blomberg).

Alumni

  • Dr A Leticia Alessandri: Postdoctoral Fellow
  • Dr Sarah Fox: PhD student and Postdoctoral Fellow
  • Dr Michela Festa: visiting Postdoctoral Fellow
  • Dr Andrew E Leitch: PhD Training Fellow
  • Dr Chris Lucas – ECAT Training Fellow
  • Dr David Dorward – PhD training fellow

Collaborators

Sources of Funding

More information on funding at Rodger Duffin's Research Explorer profile.