My research interest is how tuberculosis causes damage to patients' lungs. Tuberculosis continues to kill over 2 million people a year, primarily in the developing world, and lung disease not only causes spread from person to person but also causes most mortality and morbidity.
Within the tuberculosis research group, we integrate analysis of clinical samples with basic scientific approaches to understand the mechanisms of disease. My research focuses on how enzymes called matrix metalloproteinases drive lung cavitation. The ultimate aim is to identify new therapeutic targets to improve tuberculosis treatment, which has remained unchanged for the last thirty years.
The extracellular matrix of the lung consists of collagen and elastin fibres, which are highly resistant to breakdown. Only matrix metalloproteinases (MMPs) can degrade fibrils at neutral pH. We have shown that tuberculosis specifically up-regulates a collagenase, MMP-1. The next important question is to determine whether inhibiting this enzyme can reduce deaths from tuberculosis and allow new short course treatments.
et al., 2019, In Vitro Granuloma Models of Tuberculosis: Potential and Challenges, Journal of Infectious Diseases, Vol:219, ISSN:0022-1899, Pages:1858-1866
et al., 2019, Calcineurin Inhibitors and Variation in the Performance of Interferon-gamma Release Assays Used to Detect Tuberculosis Infection, Annals of the American Thoracic Society, Vol:16, ISSN:1546-3222, Pages:771-775
et al., 2019, Matrix metalloproteinases in pulmonary and central nervous system tuberculosis-a review, International Journal of Molecular Sciences, Vol:20, ISSN:1422-0067
et al., 2019, Matrix Metalloproteinase Inhibition in a Murine Model of Cavitary Tuberculosis Paradoxically Worsens Pathology, Journal of Infectious Diseases, Vol:219, ISSN:0022-1899, Pages:633-636
et al., 2018, Implications of Tuberculosis Reactivation after Immune Checkpoint Inhibition, American Journal of Respiratory and Critical Care Medicine, Vol:198, ISSN:1073-449X, Pages:1451-1453