Welcome to the Laboratory of Genome Stability and Innate Immunity (Zierhut Lab) at the Institute of Cancer Research in London. We study how cancer-associated genome instability activates immune signalling, and how this determines cell fate.
Our aim is to identify how chromosomal aberrations trigger intracellular immune responses, and how these control cell fate decisions. Ultimately, we aim to generate an understanding of innate immune responses during cancer development and treatment in order to suggest new therapeutic strategies.
cGAS is the major sensor of intracellular pathogen DNA, but despite the presence of endogenous DNA within host cells, self-DNA generally does not activate cGAS. We previously provided evidence that this is because the chromatin organisation of host DNA is incompatible with cGAS activation, thus silencing cGAS signalling during normal cell growth. In contrast, in response to genotoxic stress, cGAS can eventually be activated, regulating inflammatory responses, cellular senescence and cell death. Ultimately, activation of innate immunity via cGAS is critical for cancer development, chemotherapy and immune therapy.
We are currently investigating three major questions in order to understand silencing and signalling from self-DNA:
How does chromatin inactivate innate immune signalling?
How does genotoxic stress activate innate immune signalling?
How is cell fate controlled after genotoxic stress?
By understanding these questions, we hope to provide explanations for the behaviour of cancer cells during cancer development and treatment, and to reveal new therapeutic avenues. Read more details about our research here.
Summer 2021 Welcome to the lab, Negar Afshar and Rob Pickering!
26 Mar. 2021 Christian to speak at Virtually Dead Episode III: Cell Death and Inflammation.
15 Mar. 2021 Multiple post-doc positions available. Find out more here.
11 Nov. 2020 Christian to speak at Oxford University.
30 Oct. 2020 Christian to speak at SUNY Binghamton.
Laboratory of Genome Stability and Innate Immunity