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The main scientific focus of my group is the study of human T cell differentiation and longevity and whether end-stage differentiation can lead to the loss of immunity in ageing humans. Key landmarks that have been made by my group on T cell differentiation in the last 20 years include the first use of CD45R isoforms to identify primed and unprimed subsets of human T cells, the initial observation that memory populations of T cells are susceptible to apoptosis and have to be rescued by cytokines, dysfunctional apoptosis can lead to chronic inflammation and more recently, the potential role of telomere erosion in limiting human T cell memory to viruses. Throughout this time my group developed important new technologies such as 2 and 3-colour Flow-FISH which allows measuring of telomere lengths in different cell populations using flow cytometry. Furthermore, work that was aimed at understanding co-stimulatory molecule expression during CD8+ T cell differentiation involving a close collaboration with Drs. Alastair Lawson and Helene Finney at Celltech plc. resulted in the development of unique reagents. These constructs allow dissection of the complex array of signalling molecules and their respective roles in CD8 T cells subsets, specifically those close to end-stage differentiation. We are currently exploring mechanisms that regulate end-stage differentiation in primary human T cells.
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