We aim to understand how genetic differences between people impact on our ability to mount an appropriate immune response and so may contribute to susceptibility to infectious, inflammatory and autoimmune diseases. We study both rare highly penetrant mutations which may cause Mendelian disease, for example primary immunodeficiency disorders, together with more common genetic variants that have been found to be associated with multifactorial traits involving inflammation and immunity. The latter typically involve noncoding regulatory variants that alter gene expression. We are seeking to take forward the results of genetic association studies to translate into potential clinical benefit by defining causal variants, resolving their mode of action and identifying the specific modulated genes and pathways which may be therapeutic targets.
Our work combines bioinformatics with functional genomic approaches studying genetic variants in primary cells in disease relevant contexts and establishing mechanism. This includes analysis of allele-specific gene expression, expression quantitative trait mapping and detailed characterisation of how sequence diversity modulates the epigenetic and genetic control of gene expression. We have established translational programmes in the genomics of sepsis and ankylosing spondylitis together with use of genomics for drug target identification and validation.
We actively seek to promote public engagement with genomics and implementation of genomic medicine in the clinic through education, training and a multidisciplinary approach.