Prof Tracy HussellPhD

Centre Director (MCCIR)

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Research interests

The group has internationally competitive research in the following areas:

1. How immunological homeostasis is maintained in the respiratory tract.  This basic immunology programme feeds into all aspects inflammatory disease.  We have published evidence that the default state of lung innate immunity is activation and that it is restrained by the local microenvironment, predominantly by factors expressed or secreted by the respiratory epithelium. This overall hypothesis leads into the following areas of investigation:

a) Factors expressed or secreted by the respiratory epithelium that regulate innate immunity.

b) The impact of genetic deletion of factors expressed or secreted by the respiratoryepithelium on innate immune activity in the steady state and during acute inflammation.

c) Analysis of the unique phenotype of alveolar macrophages.

 

2. The consequences of altered homeostasis following resolution of acute inflammation or during allergy.  We have established models for the following infections:Influenza virus (H1N1, H3N2 and H5N1), Respiratory Syncytial virus, Streptococcus pneumoniae, Haemophilus influenzae and Pseudomonas aeruginosa, Cryptococcus neoformans and Aspergillus. All provide acute infection of varying severity depending on the dose of pathogen, the age of the host and the strain of mouse used. Further we are part of the MOSAIC consortium analysing the pathogenesis of recent avian influenza viruses in humans. The projects leading on from resolution of these acute infections include:

a) Analysis of long term alterations in innate immune subsets, particularly airway macrophages

b) Alteration of the commensal microbial flora by these acute infection (by 16s ribosomal RNA sequencing)

c) Altered epithelial and endothelial control and permeability

d) Changes in micro inhibitory RNA species in respiratory epithelial cells and macrophages

e) Parameters contributing to susceptibility to secondary bacterial pneumonia

f) control of pathogens in the allergic lung

 

3. Novel pathways of innate immune regulation in the steady state and post acute inflammation.  These novel pathways (envisaged to lead to translatable compounds and processes) include: a) TAM receptors, b) Interleukin 33 and its receptor, ST2L, c) IL-10 receptor, d) transforming growth factor beta receptor, e) micro-inhibitory RNA species, f) CD200 and its receptor and g) TREM1 and 2

4.. Therapeutic modulation of acute and chronic inflammation.We have developed pre-clinical data showing the relative advantages of a number of compounds compared to those currently in use.  For example, in collaboration with GSK we have defined a reduced infectious risk using agents that only block TNFR1 compared to etanercept (widely used in the treatment of arthritis) that blocks TNFR1 and TNFR2.  Reduced infectious risk provides new and developing reagents with a market advantage.

We have also identified OX40 blockade as a realistic replacement for anti-TNF therapy in acute infectious, and chronic autoimmune, disease.  The treatment only targets recently activated antigen specific T cells and so once again reduces the infectious risk in treated patients. This work is in collaboration with UCB Celltech.  The list continues with reagents that harness innate negative regulators such as CD200 receptor (in collaboration with Neil Barclay, Oxford), inhibition of reactive oxygen and nitrogen species (in collaboration with Storm bio, New Jersey) and we are currently trialling micro-inhibitory RNA species in smoke-induced exacerbation of human COPD (In collaboration with Trevor Hansel, Imperial College).

 

Projects

Research and projects

  1. NIHR Biomedical Research Centre: Cancer Precision Medicine Theme.

    Dive, C., Baena Chaparro, E., Blackhall, F., Bruce, I., Bundred, N., Carter, L., Clarke, R., Cook, N., Crosbie, P., Evans, D., Harris, J., Hawkins, R., Hussell, T., Illidge, T., Jayson, G., Jorgensen, C., Kirwan, C., Kostarelos, K., Krebs, M., Lorigan, P., Marais, R., Marshall, K., Metcalf, R., Payne, K., Radford, J., Somervaille, T., Springer, C., Taylor, S., Thistlethwaite, F., Viros Usandizaga, A. & Zelenay, S.

    1/04/1731/03/19

    Project: Research