IMMUNE REGULATION AND PATHOLOGY
Our aims are to understand immunity and immune responses in health and diseases. We are particularly interested in those diseases associated with abnormal antibody production. Inadequate or excessive immune responses lead to either immunodeficiencies or to autoimmune and inflammatory diseases, which place a major economic and social burden on healthcare systems and the quality of human life. The development of novel therapies for immune disease requires better understanding of the underlying cellular and molecular pathology and the identification of mechanistic pathways as potential therapeutic targets. So, we are interested in the following:
- Immune function and the consequences of genetic and molecular variation.
- Targeting the immune response in autoimmune disease and cancer.
- Classifying and treating immune disease in individuals based on molecular pathology.
B CELL SELECTION: MODELLING AUTOIMMUNITY AND SELF-TOLERANCE. We use transgenic models and other basic immunological assays to study antigen-specific B cells. This approach makes it possible for us to compare uniform populations of cells from mice with specific mutations affecting lymphocyte regulation, and track the response to foreign antigens and movement of antigen-specific cells in vivo. Some examples of our work are a study by Dr. Xijin Xu describing the role of LIN28B in B1 B cell ontogeny, and work by Dr. Rose Hodgson to investigate the role of NDRG1 in B cell tolerance and of PEPD in lupus-like autoimmunity. This work was in collaboration with Dr. Katherine Bull at the Centre for Human Genetics, Oxford.
A recent example of our work is a study by Dr. Mukta Deobagkar to investigate the role of DOCK8 in eliciting T cell help for the activation and survival of B cells, particularly when antigen amounts are limited. Current projects in the Cornall laboratory investigate how the immune system regulates the response to different forms of antigen and how B cells, in particular innate-like B1 B cells, are positively selected into the naïve repertoire during ontogeny.
B CELL DEVELOPMENT: MODELLING IMMUNODEFICIENCIES. Much of our knowledge about immune control has come from studying rare mouse and human mutations. One example of our work is the beautiful study by Dr. Consuelo Anzilotti on a human immunodeficiency caused by hypomorphic mutations in a zinc transporter SLC39A7 or ZIP7. This work was a collaboration with many groups, including Jean-Laurent Casanova and Mary Ellen Conley at Rockefeller University in New York, but primarily with Sophie Hambleton in Newcastle University. Current projects investigate the role of ZIP7 in the naïve immune repertoire and during antigen-specific responses .
IMMUNE REGULATION: DEVELOPING NOVEL THERAPEUTICS. Our final approach is to develop novel antibody-based therapeutics, which will reduce the immune or inflammatory response in human disease. This project, which is a longstanding collaboration with Professor Simon Davis at Oxford, targets superagonists against human leukocyte inhibitory receptors. To accelerate this work, we have developed a series of mice carrying human receptors and an array of novel superagonistic antibodies. https://doi.org/10.1016/j.immuni.2024.01.007
Our laboratory has been a part of the Medical Research Council Human Immunology Unit and has collaborations across the MRC Translational Immune Discovery Unit. Our work is funded by the Medical Research Council and the Wellcome Trust. The Cornall group are based at the Centre for Human Genetics.
Group Contact
Prof. Richard John Cornall, Nuffield Professor of Clinical Medicine and Head of Department
Professor of Immunology, MRC Investigator, Fellow of Magdalen College.
Old Road Campus,
Roosevelt Drive,
Headington,
Oxford,
OX3 7BN
PA 44-(0)1865-287986
Further details can be found on Richard Cornall's profile pages at the CHG and at NDM