James D Chalmers

Biography

Professor James Chalmers did his undergraduate training in Glasgow and trained in Respiratory Medicine in Edinburgh before moving to Dundee. He is a Professor and Consultant Respiratory Physician with a subspecialist interest in difficult to treat airways disease, particularly bronchiectasis, COPD, severe asthma and cystic fibrosis. As a clinical academic, he undertook an MRC training fellowship in the Centre for Inflammation Research in Edinburgh followed by a Wellcome Trust Postdoctoral Fellowship in the Division of Molecular Microbiology at the University of Dundee before establishing his own research group in 2013. Severe and disabling respiratory diseases such as bronchiectasis, COPD and severe asthma are characterised by changes in the bacterial communities in the lung (“the microbiome”), promoting neutrophil mediated inflammation with consequent lung remodelling and disease progression. There are no proven therapies to directly target neutrophilic inflammation or the lung microbiome, leaving millions of patients without effective treatment. The Chalmers group is multidisciplinary consisting of scientists, physicians, nursing, project management and informatics expertise. The groups primary objective is to find better ways of identifying lung inflammation and infection and to develop new therapies that can target this treatment resistance type of inflammation to improve patient outcomes. 

Research Interest

Improving outcomes for patients with bronchiectasis Bronchiectasis is a chronic disabling lung disease characterised by neutrophil mediated airway inflammation and chronic bacterial infection. It has been described as an “orphan disease” due to a lack of research and available treatments. In 2012 with colleagues from the European Respiratory Society, James established the European Bronchiectasis Network and Registry (EMBARC). This network now links more than 150 centres across Europe in performing bronchiectasis research studies. The EMBARC registry (www.bronchiectasis.eu) is funded by the European Union Innovative Medicines Initiative and supported by the European Respiratory Society and Charities. Work in the Dundee group has included the development of the first validated clinical prediction tool for bronchiectasis (www.bronchiectasisseverity.com), identification of bacterial load as the key driver of neutrophil mediated inflammation and identification of several genetic, inflammatory and clinical risk factors for disease progression. Our current laboratory work focusses on understanding the inflammatory response, including how neutrophil behaviour is altered in bronchiectasis towards a phenotype favouring the formation of neutrophil extracellular traps and impaired bacterial killing. Studies are underway to develop diagnostics for patient stratification as well as clinical trials of novel therapies to reverse neutrophil dysfunction. To facilitate these studies we have established one of the worlds largest biorepositories for bronchiectasis (The TAYBRIDGE cohort) which includes longitudinal serum, DNA and sputum samples from over 600 well characterised patients. Targeting the lung microbiome The airways harbour diverse polymicrobial communities that are altered in disease and contribute towards the development and persistence of neutrophil mediated inflammation. We have established in house facilities to sequence the upper and lower airway microbiome for bacteria and other microorganisms and are now applying these technologies to large populations of patients with COPD, bronchiectasis and severe asthma. Most importantly, we are studying the response of the microbiome to common therapies such as inhaled corticosteroids, bronchodilators and antibiotics in controlled clinical trials with the aim of evaluating whether the airway microbiome and neutrophilic inflammation can be therapeutically modulated. Work in this area is funded by the Wellcome Trust, Scottish Government Chief Scientist Office and the pharmaceutical industry. Patient phenotyping in COPD Using a combination of biomarkers, genetics, clinical characteristics and the airway microbiome, it is possible to identify patients with COPD that have distinct outcomes and distinct pathophysiology- so called endotypes. The objective of this workstream is to better target treatments for COPD, reducing the harms of treatment with drugs such as inhaled corticosteroids while maximising benefits by selecting the “right patients”. Work in this area is funded by the Scottish Government Chief Scientist Office, Charities and the pharmaceutical industry. Antimicrobial resistance and antibiotic stewardship AMR is a public health crisis. Respiratory infections are the leading cause of antibiotic prescription both in the community and in hospitals. As a result, we have a responsibility to target antbibiotic treatments appropriately. As part of this workstream we will use some of the tools described above such as patient phenotyping and diagnostics to try to reduce unnecessary antibiotic use. In-vitro work in this area includes studies in to the type VII secretion system of Staphylococcus aureus (including MRSA) to identify new therapies. Work in community-acquired pneumonia seeks to understand the drivers of antibiotic resistance and the clinical impact of AMR, as well as the role of commonly used antibiotics like macrolides. Our group is very grateful for the generous support of the following funders -          Wellcome Trust -          Medical Research Council -          European Union Innovative Medicines Initiative -          Scottish Government Chief Scientist Office -          National Institute for Health Research -          Tenovus Scotland -          Astrazeneca -          Glaxosmithkline -          The European Respiratory Society