Cytotoxic lymphocytes recognise and kill cancerous and virus-infected cells through the cytotoxic granule exocytosis pathway. Cytotoxic granules store a pore-forming protein, perforin, and serine proteases, granzymes. Once released, perforin transiently disrupts a target cell membrane, thus permitting the delivery of granzymes into the cytosol, where they initiate various apoptotic death pathways. This is a fundamental homoeostatic process; when disrupted, it has catastrophic consequences leading either to fatal hyperinflammation or, in milder cases, resulting in haematological malignancies in childhood or adolescence.
Exploring the biology of cytotoxic lymphocytes is critical for understanding the fundamental principles of immunity, predisposition to blood cancers and immune deficiency. We take a multidisciplinary approach that encompasses immunology, biochemistry, structural biology, cell biology, and genetics to answer these important questions.
Current projects
We investigate the regulation and effector function of cytotoxic lymphocytes, including cytotoxic granule exocytosis and biogenesis, the biology of granzymes (with Prof Joe Trapani), the molecular bases of congenital immune deficiencies due to impaired function of cytotoxic lymphocytes, lysosomal storage diseases (with Prof Mark Walterfang), and the effector mechanism of CAR T cells.
Related pages