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Research interests

Group: The Wülfing laboratory

The research focus of the Wuelfing laboratory is to understand how T cell activation is controlled in health and the immune response in cancer. To gain unique access to the system-wide, complex processes driving T cell activation, we directly determine signalling as it occurs in time and space inside primary T cells activated by antigen presenting cells with large-scale live cell imaging approaches.

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Activating T cells forming deep invaginations with antigen presenting cell (APC) membrane still attached, as visualized by electron microscopy.

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Live cell imaging with the CD48 APC ligand for the CD2 T cell costimulatory receptor tagged with green fluorescent protein.

The key physiological problem we are addressing is the suppression of cytotoxic T cell function in the tumour microenvironment. Cytotoxic T cells are commonly found in tumours. They have the ability to kill tumour target cells. Yet, this ability is commonly suppressed in the tumour microenvironment by multiple, often redundant mechanisms. We have established in vivo validated, three-dimensional tissue culture apporaches to gain experimental access to murine and human cytotoxic T cell suppression in vitro. Using these approaches, we investigate mechanisms of action of T cell inhibitory receptors, such as PD-1 and TIM-3, of soluble mediators such as adenosine and of suppressive cell types such as cancer-associated fibroblasts. In collaboration with industrial partners we investigate mechanisms of action of T cell-focussed therapeutics. 

The research is described in more detail on our laboratory website http://www.bristol.ac.uk/cellmolmed/research/infect-immune/wuelfing/

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