Dr Jenkins' research focuses on the mechanism by which injury leads to scarring in the lung. Lung scarring is the central process leading to disability and death in people with Idiopathic Pulmonary Fibrosis, and also occurs in diseases such as chronic asthma where it promotes airway remodelling and impaired lung function. Following injury to the lung various cells activate TGFb via integrins in a spatially restricted manner. The activated TGFb then leads to cellular changes that promote the development of scarring. Much of the work is focused on two integrins in two cell types within the lung.
The major focus of the laboratory is on pathways that activate TGFb via the epithelially restricted avb6 integrin. His group has identified a G protein mediated signalling pathway that responds to a variety of injurious stimuli leading to TGFb activation. Current work is focused on:
a) mechanistic studies investigating other activators of epithelial TGFb such as neutrophil elastase and influenza virus
b) modelling studies that will determine the importance of this pathway in lung injury and fibrosis in vivo.
c) translational studies developing the molecules involved in this pathway for use as biomarkers and therapeutics in people with IPF.
Dr Jenkins' lab is also investigating the role of the avb5 integrin mediated TGFb activation in airway smooth muscle cells. Work in this area focuses on the hypothesis that cellular stretch associated with airway narrowing in asthma may activate TGFb and promote airway remodelling and scarring.
TATLER, A.L., JOHN, A.E., JOLLY, L., HABGOOD, A., PORTE, J., BRIGHTLING, C., KNOX, A.J., PANG, L., SHEPPARD, D., HUANG, X. and JENKINS, G., 2011. Integrin avβ5-mediated TGF-β activation by airway smooth muscle cells in asthma Journal of Immunology. 187(11), 6094-6107 COWARD, W.R., WATTS, K., FEGHALI-BOSTWICK, C.A., JENKINS, G. and PANG, L., 2010. Repression of IP-10 by interactions between histone deacetylation and hypermethylation in idiopathic pulmonary fibrosis Molecular and Cellular Biology. 30(12), 2874-2886 XU, M.Y., PORTE, J., KNOX, A.J., WEINREB, P.H., MAHER, T.M., VIOLETTE, S.M., MCANULTY, R.J., SHEPPARD, D. and JENKINS, G., 2009. Lysophosphatidic acid induces αvβ6 integrin-mediated TGF-β activation via the LPA2 receptor and the small G protein Gαq American Journal of Pathology. 174(4), 1264-1279
NAVARATNAM, V., FLEMING, K.M., WEST, J., SMITH, C.J.P., JENKINS, R.G., FOGARTY, A. and HUBBARD, R.B., 2011. The rising incidence of idiopathic pulmonary fibrosis in the UK Thorax. 66(6), 462-467