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Research Fellows Directory

Pascal Meier

Professor Pascal Meier

Research Fellow


Institute of Cancer Research

Research summary

Inflammation and cell death are ancient processes of fundamental biological importance that enable survival and adaptation during infection and injury. Tumour necrosis factor (TNF) is the prototypical proinflammatory cytokine that signals, through its type 1 receptor (TNF-R1), either cell survival, cell proliferation or cell death. TNF stimulates an inflammatory response whose 'purpose' is to remove the source of the disturbance, allowing the host to adapt to an abnormal condition, and, ultimately, to restore functionality and homeostasis to the tissue. However, when deregulated, inflammation can drive chronic remodelling and tissue repair, which contributes to chronic inflammatory diseases, cancer and treatment failure. It is now clear that many chronic inflammatory diseases are caused by aberrant cytokine-induced cell death, yet the molecular players that regulate this process are unknown. Even though TNF was originally identified as a cytokine that potently induces cell death of experimental cancers, it remains unclear what switches the response to TNF from inflammation to cell death. We have addressed an issue that has remained enigmatic for the last 40 years. Over the last year we now have resolved what determines whether an inflammatory cytokine, such as TNF, stimulates either an immune response or triggers rapid cell death? This discovery is very important as an inflammatory tumour microenvironment can drive cell survival and dictate the aggressiveness of tumours, or influence the response to therapy. If we were able to convert the tumour promoting inflammatory pathways into cytotoxic ones, we would be able to exploit cytokines of the tumour microenvironment to kill tumour cells. Moreover, cells that die in response to TNF initiate adaptive immunity by providing both antigens and inflammatory stimuli for dendritic cells, which in turn activate immune cells through a process called antigen cross-priming.

Grants awarded

Ubiquitin mediated regulation of cell survival and cancer

Scheme: Wolfson Research Merit Awards

Dates: Apr 2012 - Mar 2017

Value: £50,000

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