(MRC DTP) Identification of underlying immune dysfunction in psoriasis to allow targeted patient stratification

Psoriasis is a relatively common inflammatory skin disease affecting 1-3% of the population. It can vary in severity, the skin sites affected, stimuli triggering a disease episode and the age of onset of disease. It is therefore likely that psoriasis is actually comprised of multiple similar conditions that have a common outcome of skin inflammation, but may be caused by different environmental and underlying immune system factors.

Psoriasis is known to be T cell driven and involves the cytokines IL-23 and IL-17, but the underlying cause of this enhanced immune response remains elusive. In the past 10 years, treatment for moderate to severe psoriasis has been revolutionised by the introduction of biologics targeting the IL-23/IL-17 pathway, but not all patients respond well to these treatments, there can be severe side effects, and they have a large cost. There is therefore a need for better targeting of treatments to the patient groups that will most benefit from these therapies.

This project will use RNA seq analysis of immune cells from patient skin biopsies from sites that have recovered from psoriasis, and sites that have never been affected by disease. This will identify changes in the immune cell transcriptome that underlie disease and those that are a consequence of inflammation failing to resolve. Mechanistic insights will be gained using pre-clinical models of inflammatory skin disease. Together, this will supply insight into factors underlying the hyperactive immune response driving psoriasis, which will allow patient stratification to be based on the underlying causes of disease. Findings from this project may also suggest novel therapeutic targets, which could benefit those with particular subsets of psoriasis.

http://www.mccir.ls.manchester.ac.uk/research/skininflammation/
http://www.mig.ls.manchester.ac.uk/people/amysaunders/
https://www.research.manchester.ac.uk/portal/Christopher.Griffiths.html
http://research.bmh.manchester.ac.uk/skin/staff/ChrisGriffiths/


This is a potential studentship to be funded via the MRC Doctoral Training Programme. Projects under this scheme are competitively funded; i.e. there are more projects advertised than available.