Functional genomics of immunity
Our research aims to understand how genetic variation impacts genes critical to mounting an appropriate immune response and may contribute to susceptibility to infectious, inflammatory and autoimmune diseases. There is a wide spectrum of genetic variation modulating inter-individual differences in immune response with functional consequences ranging from severe primary immunodeficiency disorders to risk of multifactorial traits involving inflammation and immunity. Our recent discovery that non-coding regulatory variants are major drivers of diversity in the immune response transcriptome identifies an important mechanism for this.
The disease relevance of regulatory variants is highlighted by genome-wide association studies (GWAS) in which the majority of reported associations have been found to involve non-coding variants. To take forward the results of GWAS and translate into potential clinical benefit, we now need to define causal regulatory variants, resolve their mode of action and identify the specific modulated genes and pathways which may be therapeutic targets.
We have established translational programmes in the genomics of sepsis as part of the Genomic Advances in Sepsis study and in ankylosing spondylitis.We aim to promote use of genomics for drug target identification and validation, public engagement with genomics and implementation of genomic medicine in the clinic through education, training and a multidisciplinary team approach.
Wellcome Trust, Arthritis Research UK, Psoriasis Society, Oxford Biomedical Research Centre
Keywords: Gene expression, regulatory variants, genome editing, MHC, immunity, inflammation, sepsis, transcription, single nucleotide polymorphism, ankylosing spondylitis, eQTL, functional genomics, epigenomics, drug targets
Lees JA. et al, (2019), Nature Communications, 10
Taylor J. et al, (2019), Genome Medicine, 11
Al-Mossawi H. et al, (2019), Nature communications, 10
GENETIC DETERMINANTS OF TRANSCRIPTIONAL VARIATION IN PRIMARY HUMAN MONOCYTES ACROSS MULTIPLE CONTEXTS
Nassiri I. et al, (2019), EUROPEAN JOURNAL OF HUMAN GENETICS, 27, 1713 - 1714