Intravital Microscopy and Gene Expression (IMAGE) Lab

B cells make antibodies to protect us from infection by pathogens, such as bacteria and viruses. We harness the power of our own B cells every day, by using vaccines to generate long-lived plasma cells and memory B cells that are taught to remember which pathogens are threats through a selection process inside structures called germinal centres. These basic biological processes keep us alive because, without B cells and antibodies, we are prone to recurrent infections.

B cells can sometimes be harmful and make antibodies that inadvertently attack our own body. These autoantibodies are made by self-reactive B cells and can cause diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis and Sjögren’s syndrome. Furthermore, B cells have been implicated in autoimmune diseases, such as multiple sclerosis (MS), which were previously thought of as T cell-mediated diseases, although the mechanisms are unclear.

Finally, antibodies made by B cells can be engineered and mass-produced as therapeutic drugs, such as the immune checkpoint inhibitors used to treat some types of cancers. Intriguingly, the presence of ectopic germinal centres and B cell and plasma cell infiltration appear to predict favourable responses to immune checkpoint block

Our lab uses intravital microscopy to observe and decipher the complex in vivo cellular dynamics required for these biological processes and complements this with single-cell genomic approaches to determine the molecular drivers. We study these processes iteratively in animal models and patient samples to inform and refine our understanding, with a view to developing precision immunology therapies. The IMAGE Lab is also focused on understanding the process of cancer cell dormancy in bone, the role of osteoclasts and osteomorphs in bone homeostasis and diseases such as cancer metastatic relapse, osteoporosis and other complex diseases including atherosclerosis. These may represent ‘macrophage-opathies’ – or diseases that are caused by macrophage dysfunction and may be treated by targeting them.

Current lab projects

Our current projects are examining, in broad terms, questions such as:

• What is the role of macrophages in the germinal centre and how does this impact the pathogenesis autoimmune diseases such as SLE?
• What is the best way to generate long-lived memory against vaccine antigens that maximises both the quantity and quality of the antibody response?
• What is the long-lived plasma cell niche in bone and how does this impact plasma cell survival and the durability of vaccine-mediated protection?
• What is the dormant cancer cell niche in bone and how does it reprogram cancer cells to enter a dormant state?
• What is the source of interferon signalling in dormant cancer cells in bone?
• What is the driver of osteoclast recycling and osteomorph formation in bone?
• What is the role of osteomorphs in rheumatoid arthritis and other ‘macrophage-opathies’?

We are always on the lookout for curious thinkers who are not afraid to fail, so please contact us if you are interested in joining the IMAGE Lab.