|Knight Group 2015|
|Cover art for Human Genetic Diversity published by OUP|
|Overview of the human Major Histocompatibility Complex on chromosome 6p21|
Professor of Genomic Medicine
My 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.
Our goal is to leverage recent advances in human genetics to improve understanding of biological process in immune disease pathogenesis, validate drug targets and advance opportunities for precision medicine.
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 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 approach.
Erratum: Transcriptomic Signatures in Sepsis and a Differential Response to Steroids. From the VANISH Randomized Trial (American Journal of Respiratory and Critical Care Medicine (2019) 199 (980–986) DOI: 10.1164/rccm.201807-1419OC)
Antcliffe DB. et al, (2022), American Journal of Respiratory and Critical Care Medicine, 206, 1572 - 1573
Association between age and the host response in critically ill patients with sepsis.
Michels EHA. et al, (2022), Critical care (London, England), 26
Divergent trajectories of antiviral memory after SARS-CoV-2 infection
Tomic A. et al, (2022), Nature Communications, 13
Epigenomic analysis reveals a dynamic and context-specific macrophage enhancer landscape associated with innate immune activation and tolerance
Zhang P. et al, (2022), Genome Biology, 23
Identification of host–pathogen-disease relationships using a scalable multiplex serology platform in UK Biobank
Mentzer AJ. et al, (2022), Nature Communications, 13