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Project Overview:

 Our immune response is designed to protect us from danger including infection, tissue injury, cellular stress and tumour invasion.  We are investigating how inflammation is triggered by endogenous danger signals compared to exogenous pathogenic molecules, with a major focus on how dysregulation of these pathways drives chronic inflammation in autoimmune, fibrotic and metabolic diseases, and enables tumors to escape immune elimination.   Our research explores a new model of immune surveillance, where crosstalk between the extracellular matrix, stromal cells and immune cells plays a critical role in orchestrating immunity.

The extracellular matrix is essential for life; this 3D macromolecular network provides structural support to tissues and environmental signals that dictate cell behaviour.  Matrix molecules that are not expressed in healthy tissues, but which are induced upon tissue injury or cellular stress, create a pro-inflammatory niche that supports resident stromal cells and infiltrating immune cells, providing mechanical cues and patterning soluble signalling factors.  Within this distinct microenvironment, immuno-modulatory matrix molecules also directly activate site-specific inflammatory programmes designed to drive controlled inflammation, promote tissue repair and restore homeostasis.

Our work has revealed significant mechanistic differences underlying immune responses driven by endogenous matrix triggers compared to host defence against pathogen invasion.  We also demonstrated how persistent expression of immuno-modulatory matrix molecules drives chronic inflammation in autoimmune and fibrotic diseases, and, more recently, how successful tumors exploit these properties of the matrix to switch the tumor microenvironment from an immunogenic to a tolerogenic state.

Building on these data we are using an interdisciplinary approach to better understand the precise immunological roles of distinct components, and compartments, of the extracellular matrix, and to determine whether targeting matrix molecules can effectively re-programme aberrant inflammation, adding new ammunition to the fight against inflammatory disease.

Training:

The Kennedy Institute is a world-renowned research centre, housed in a brand new, state-of-the-art facility at the University of Oxford.  Training will be provided in traditional biochemical, structural and molecular techniques, as well as cutting edge cellular immunology, imaging, computational genomics, genome editing and disease models. 

NDORMS had a vibrant post doc community that offers many opportunities for career development.  The Kennedy Institute runs a weekly seminar series hosting world leading speakers; all staff are encouraged to attend and to meet with speakers.  Staff will present their own data regularly within the department and attend external conferences globally.  Staff also benefit from University mentoring schemes and formal training including in undergraduate tutoring at Oxford, techniques for successful teaching and lecturing, and graduate student supervision.  

Relevant Publications