We aim to determine the development, regulation and function of B and T cell populations in health and immunological diseases. This will lead us to an understanding of why certain individuals are at greater risk of developing immunological disease, as well as to identify potential therapeutic targets or improved clinical management. This is achieved through the development and application of novel experimental and computational approaches, working in partnership with a global network of clinicians, immunologists and sample cohorts.
HOW ARE DIFFERENT B CELL POPULATIONS DEVELOPMENTALLY LINKED IN HUMAN HEALTH?
We are investigating the generation, function and plasticity of B cell populations in human health. In particular, we are interested in how different lymphocyte subsets are developmentally linked and differences in function, and therefore providing a platform to understand how B cell fate may be different in human disease.
IMMUNO-SURVEILLANCE IN CANCER
There is accumulating evidence for the role of both T and B cells in modulating immune responses to both solid tumours and haematological malignancies. We are investigating the contributions, function and heterogeneity of B and T cells on the immune responses to tumours and their potential role in cancer detection and treatment.
HOW IS B CELL REPERTOIRE AND FUNCTION DIFFERENT IN AUTOIMMUNE DISEASE AND LEUKAEMIA
B cells, and the antibodies they produce, have long been associated with autoimmune and inflammatory disease. We have developed improved technical approaches that permits increased analysis of the B cells in the context of disease. We have performed the first systematic comprehensive analysis to determine the global differences in B cell repertoire between autoimmune diseases and relationship to disease pathology in pre- and post-therapy patients. Diseases include:
- Systemic lupus erythematosus (SLE)
- IgA vascultis (formally Henoch Schönlein purpura, HSP)
- Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV)
- Eosinophilic granulomatosis with polyangiitis (EGPA)
- Crohn's disease (CD)
- Behcet’s disease (BD)
- Chronic lymphocytic leukaemia (CLL)
WHAT IS THE EFFECT OF GENETIC AND ENVIRONMENTAL VARIATION ON B AND T CELL FATE?
We are integrating genomics, transcriptomics, and metabolomics data, serological, B /T cell repertoire and viromics datasets to investigate the effect of both genetic variation and environmental factors on B cell fate, regulation, and the relationship to disease susceptibility.
HOW ARE B /T CELL POPULATIONS RECONSTITUTION DURING AND AFTER IMMUNOMODULATORY THERAPY?
We have shown that B cell depletion therapy and/or immunosuppression therapy in patients with a range of autoimmune diseases is associated with significant changes in B cell repertoires reflecting different mechanisms of B cell modulation. However, the effect of different therapeutic interventions on B and T cell function and the resulting reconstitution is not well understood, particularly in relationship to patient prognosis. We are applying single-cell genetic technologies to investigate the determinants of B cell persistence and reconstitution during and after therapy in autoimmune disease. This information may be used to develop potential biomarkers of resistance to therapy and to determine potential therapeutic interventions that could be combined with the current standard of care that could target persistent clones in autoimmune diseases.
We aim to develop novel experimental and computational tools to investigate the function of immune responses through advances in high-throughput and genetic technologies. These technologies can be readily applied to existing cohorts to investigate the immune system from unique perspectives.