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., Mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology, Plos Pathogens, ISSN:1553-7366
et al., Epigenetic regulation of Matrix metalloproteinase-1 and -3 expression in mycobacterium tuberculosis infection, Frontiers in Immunology, ISSN:1664-3224
et al., 2017, A Bioengineered Three-Dimensional Cell Culture Platform Integrated with Microfluidics To Address Antimicrobial Resistance in Tuberculosis, Mbio, Vol:8, ISSN:2150-7511
et al., 2017, Early Secretory Antigenic Target-6 Drives Matrix Metalloproteinase-10 Gene Expression and Secretion in Tuberculosis, American Journal of Respiratory Cell and Molecular Biology, Vol:56, ISSN:1044-1549, Pages:223-232
et al., 2017, Corticosteroids and infliximab impair the performance of interferon-γ release assays used for diagnosis of latent tuberculosis., Thorax