Imperial College London

DrPaulElkington

Faculty of MedicineDepartment of Medicine

Honorary Clinical Senior Lecturer
 
 
 
//

Contact

 

+44 (0)20 3313 2733p.elkington Website

 
 
//

Location

 

8N23Commonwealth BuildingHammersmith Campus

//

Summary

 

Summary

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.  

 

  Extensive lung destruction caused by tuberculosis

Extensive lung destruction caused by tuberculosis

Publications

Kubler A, Larsson C, Luna B, et al., 2016, Cathepsin K Contributes to Cavitation and Collagen Turnover in Pulmonary Tuberculosis, Journal of Infectious Diseases, Vol:213, ISSN:0022-1899, Pages:618-627

Ostridge K, Williams N, Kim V, et al., 2016, Relationship between pulmonary matrix metalloproteinases and quantitative CT markers of small airways disease and emphysema in COPD., Thorax, Vol:71, Pages:126-132

Belton M, Brilha S, Manavaki R, et al., 2016, Hypoxia and tissue destruction in pulmonary TB., Thorax

Mansour S, Tocheva AS, Cave-Ayland C, et al., 2016, Cholesteryl esters stabilize human CD1c conformations for recognition by self-reactive T cells., Proc Natl Acad Sci U S A, Vol:113, Pages:E1266-E1275

Ong CWM, Elkington PT, Brilha S, et al., 2015, Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis, Plos Pathogens, Vol:11, ISSN:1553-7366

More Publications