Our immune system is constantly confronted with the decision of whether to launch an immune response or not. On one hand, these responses are essential for repelling pathogens or cancers. On the other hand, they can be detrimental when directed against our own tissues and cause autoimmune disease.
Our laboratory studies how the immune system makes these decisions. We are interested in how cell death is involved in immunological tolerance and responses to infection. By understanding the ‘choreography’ of immune cell death, we seek to design better treatments for immune disorders and cancer.
Our vision is to elucidate the mechanisms of immunological tolerance to improve human health.
Our mission is to make fundamental discoveries about immune function that create new diagnostics and treatments for disease.
The Gray Lab has made notable contributions to the understanding of how the thymus makes T cells, the molecular control of immunological tolerance and therapies that enlist the immune system to treat cancer.
We have pioneered:
FOXP3+ regulatory T (Treg) cells are essential for restraining immune function. Their antagonism of autoimmune responses is crucial for health, but they also block responses to chronic infection and cancer. We are interested in how cell death processes shape the homeostasis of Treg cells with a view to modifying them to tailor immune responses. We have discovered the molecular control of Treg cell apoptosis under steady-state conditions (papers #2, 6, 7, 8) and recently defined a new pathway controlling the population during inflammation. This project will explore how to engage Treg cell death to improve responses to cancer and infection.
Dr Charis Teh, Dr Lucille Rankin, Dr Alissa Robbins
In this project, we aim to direct new therapies for treating chronic lymphocytic leukaemia (CLL) and other blood cancers by using CyTOF and high parameter flow cytometry to resolve cell death pathways in millions of individual cancer cells from patients. By understanding how cancerous cells are impacted by new targeted therapies and adapt to resist them, we will be able to inform more effective treatments for CLL and other blood cancers (papers #3, 4).
Dr Charis Teh, Ms Tania Tan, Ms Mengxiao Luo
The thymus is the exclusive site for differentiation of haematopoietic progenitors into the various T cell lineages. Curiously, although the thymus is essential for adaptive immunity, it is easily damaged and undergoes age-related atrophy to become virtually non-functional in adults. However, the thymus can be induced to regenerate and restore T cell immunity. This project focuses on the unique epithelial cells of the thymus that govern these processes. We use cutting edge imaging approaches to resolve how the thymic epithelium changes during involution and thymic regeneration to better understand how immune function might be restored (papers #1 and #5).
Ms Kelin Zhao
We are a multidisciplinary, highly motivated team committed to elucidating the molecular and cellular basis of immunological tolerance. We collaborate closely with multiple groups at WEHI, The Peter MacCallum Cancer Center, Columbia University (USA) and The University of Cambridge (UK).