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Professor Derek Macallan’s group are using non-radioactive isotope tracers to discover the secrets of human immune homeostasis.
In order to address how human immune cells are maintained over long periods of time, Professor Macallan’s group have developed and applied methods to measure rates of in vivo proliferation for immune cells which can be applied in human clinical studies. Subjects are asked to drink harmless non-radioactive isotope tracers; either deuterium-labelled water (“heavy water”) or deuterium-labelled glucose.. When cells divide in the presence of these labelling molecules, their DNA is labelled with an isotopic fingerprint. Blood sampling, cell sorting and gas-chromatography mass-spectrometry then allow us to then define the turnover rates of specific subpopulations. Combining this experimental approach with mathematical modelling (in collaboration with Dr Becca Asquith at Imperial College London) allows us to tease apart not just the way in which cell populations are maintained but also their likely relationships to one another.
Demonstrating that “stem cell memory cells” are mostly high-turnover transient cells pivotal in the generation of immune memory (in collaboration with Cardiff University)
Clarifying the relationship between classical, intermediate and non-classical monocytes (with Dr Yona, UCL)
Exploring the survival of B cells in Chronic Lymphocytic Leukaemia (with King’s College, London)
Ahmed R et al. Human Stem Cell-like Memory T Cells Are Maintained in a State of Dynamic Flux. Cell Reports. 2016;17(11):2811-2818. doi: 10.1016/j.celrep.2016.11.037
Patel AA et al. The fate and lifespan of human monocyte subsets in steady state and systemic inflammation. J Exp Med. 2017;214(7):1913-1923. doi: 10.1084/jem.20170355
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