Supervisor View Full Details

• genetics, genomics and molecular biology
• infectious disease and the immune system

• Medicine

• Respiratory Medicine

I have a strong track record in translational research and have published widely in the areas of cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), emphysema and lung inflammation. My laboratory is now recognized as one of the major units investigating the protease-anti protease balance in lung disease. The unit also has an international reputation in the areas of neutrophil activation, ER stress, airway signal transduction and more recently post translational modification of defense proteins in lung disease.
I have placed strong emphasis on the translation of my research findings to patient care and a substantial volume of my work has led to significant interactions with pharmaceutical companies worldwide. Recent examples of my research include the publication of a novel biomarker for identification of fungal-sensitization in patients with CF (J Allergy Clin Immunol, 2016), and how treatment with the ion channel potentiator ivacaftor normalized CF neutrophil ion levels and bacterial killing (Blood, 2014). In 2015, I was principle investigator of a study investigating the efficacy of alpha-1 proteinase inhibitor augmentation treatment for AATD (Lancet) and have intensely published on the ability of this treatment to correct neutrophil function (J Clin Invest, 2010; Sci Transl Med, 2014). In addition, my laboratory was the first to definitively show increased risk of COPD in people heterozygous for AATD who smoke (Am J Respir Crit Care Med. 2014).

Chronic obstructive pulmonary disease (COPD), which includes emphysema and chronic bronchitis, is an inflammatory airway disease, the incidence and mortality of which is increasing every year. Currently there is no cure. Research on the identification of biomarkers that can be effectively used to evaluate respiratory impairment and patient response to pharmacologic treatments is central to effective care.
Activated neutrophils recruited to the airways play a key role in the pathological immune response seen in COPD. Dysregulated neutrophil activity has been linked to progression of autoimmune diseases such as rheumatoid arthritis, however, a role for neutrophil driven autoimmunity in COPD is under-explored. The aim of this pioneering study is to investigate whether airway resident neutrophils cause post-translational protein (PTP) modifications affecting the processing of self-antigens leading to the development of autoimmunity. By recruiting COPD patients at different disease stages of COPD our objective is to fully determine the spectrum of PTPs in the airways and whether these changes initiate autoimmunity as demonstrated by the development of autoantibodies.
It is expected that the results of this research will provide an autoantibody panel of diagnostic potential that may benefit early diagnosis of COPD. Moreover, this groundbreaking translational research will actively recruit patients with alpha-1 antitrypsin deficiency, the only genetic risk factor for developing COPD, and will apply the discoveries generated to examine how treatment with alpha-1 proteinase inhibitor augmentation therapy leads to a decrease in posttranslational alterations, which will be of importance for a broad spectrum of autoimmune and pulmonary disorders.