Our division works across five major research areas and we are able to draw on a variety of computational, laboratory and clinical methods to pursue our goals.
Oxygen is central to life and we are interested in the sensing machinery, in particular hypoxia-inducible factor (HIF). HIF regulates DNA transcription in response to changes in oxygenation and shapes many aspects of behaviour at both the cellular and whole-organisms level. It contributes to a range of cardiovascular and renal diseases, as well as the most common form of kidney cancer, clear cell renal cell carcinoma. We use multidisciplinary collaborative approaches to develop novel small molecules to target hypoxia-signaling as potential therapeutics. We are also investigating the function of HIF in humoral immunity.
Signalling by tumour necrosis factor (TNF) mediates immunity and contributes to vascular disease. We are scrutinising its role in kidney inflammation and transplant rejection by using cell culture systems and histological analysis of primary human tissues. In the kidney, tissue-specific immunity is unusual as this organ presents a unique tissue environment for resident immune cells that are exposed to regional hypersalinity and hypoxia. Using single cell approaches, we are investigating the immune landscape of human kidneys in health and disease.
IgG antibodies play a pathogenic role in a number of autoimmune diseases and in transplant rejection. Our experimental medicine investigates the use of novel B cell targeted immunosuppressants in transplantation and uses murine models, primary human cells and tissues, and two-photon microscopy to investigate the cellular effector functions of IgG via Fc gamma receptors.
We also use genomic and transcriptomics to study autoimmunity, and have prospectively recruited and monitored cohorts of patients with autoimmune diseases for more than ten years (with a focus on small vessel vasculitis, systemic lupus erythematosus and inflammatory bowel disease). Our transcriptomics studies of peripheral blood immune cell subsets allow us to identify biomarkers/signatures that are predictive of long-term outcomes. PredictImmune Ltd is a university spin-out company based on this research, and provides tools that guide physicians in the treatment of patients with immune-mediated disease. We lead international consortia that perform genome-wide association study (GWAS) in vasculitis, identifying novel genetic associations that inform our understanding of disease pathogenesis. These have led to the first study of B cell depletion therapy in vasculitis and resulted in subsequent Phase III studies and drug registration.