Our division works across five major research areas.
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 molecule hypoxia signalling targeting agents with therapeutic potential. We are also investigating the function of HIF in humoral immunity.
Tumour necrosis factor (TNF) mediates immunity and contributes to vascular disease. We are scrutinising its role in kidney inflammation and transplant rejection, using cell culture systems and histological analysis of primary human tissues. .
We have prospectively recruited and monitored cohorts of patients with autoimmune diseases (with a focus on small vessel vasculitis, systemic lupus erythematosus, inflammatory bowel disease) for more than ten years. Transcriptomics studies of peripheral blood immune cell subsets have allowed 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 to guide physicians in the treatment of patients with immune-mediated disease. We have also led international consortia to perform genome-wide association study (GWAS) in vasculitis, identifying novel genetic associations that inform our understanding of disease pathogenesis.
IgG antibodies play a pathogenic role in a number of autoimmune diseases and in transplant rejection. We have used an experimental medicine study to investigate the use of novel B cell targeted immunosuppressants in transplantation, and use primary human cells and tissues, as well as murine models and two-photon microscopy to investigate the cellular effector functions of IgG, mediated by Fc gamma receptors.
Tissue-specific immunity in the kidney (Dr Menna Clatworthy). The kidney presents a unique tissue environment for resident immune cells, with regional hypersalinity and hypoxia. We are investigating the immune landscape in human kidneys in health and disease using single cell approaches. We are also interested in using transcriptomics and image analysis of pre-implantation kidney biopsies to develop predictors of long-term outcome.