Welcome to the Laboratory of Genome Stability and Innate Immunity at the Institute of Cancer Research in London. We study how cancer-associated genome instability activates immune signalling, and how this determines cell fate.
Overview
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:
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How does chromatin inactivate innate immune signalling?
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How does genotoxic stress activate innate immune signalling?
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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.
News
May 2024 New pre-print from the lab: A microscopy reporter for cGAMP reveals rare cGAS activation following DNA damage, and a lack of correlation with micronuclear cGAS enrichment
Dec. 2023 New review article by Christian on potential cGAS functions in DNA damage responses, DNA replication and DNA repair.
23rd Nov. 2023 Christian to speak at the Pasteur International Cancer Conference 2023.
2nd Nov. 2023 Christian to speak at Barts Cancer Institute.
27th Oct. 2023 Christian to speak at the Nucleic Acids Immunity conference in Dresden.
16th Oct. 2023 Christian to speak at the Medical University of Innsbruck.
Sept. 2023 We will be starting a new project funded by Breast Cancer Now. Read more here.
Sept. 2023 New comment piece by Christian on cGAS functions in a hematological model of genome instability (Dressel et al., 2023).
18th May 2023 The lab goes to Oxford to discuss innate immunity.
11th May 2023 Christian to speak at the Medical University of Vienna.
Apr. 2023 We are the ICR's Easter Egg Hunt champions!
4th April 2023 Christian to speak at the Institut Curie.
Jan. 2023 Welcome to the lab, Arjun Udupa!
Nov. 2022 Lauren Davies aces her transfer viva!
Oct. 2022 Welcome to the lab, Odysseus Grünert!
Oct. 2022 Congratulations to Alyssa for obtaining A+ results for both her thesis and her viva!
2 June 2022 Christian to speak at the Annual Meeting of the Association for Radiation Research.
May 2022 Welcome to the lab, Alyssa Nicholls!
May 2022 Many congratulations to Jeff Zhang for passing his thesis and viva with As!
Apr. 2022 We moved into our new lab space!
4 Feb. 2022 Christian to speak at the WUSTL Center for Genome Integrity.
Jan. 2022 Welcome to the lab, Zhang Qingyang.
10 Dec. 2021 Federico awarded for his excellent PhD thesis.
3 Dec. 2021 Christian to speak at Stanford University.
2 Nov. 2021 Christian to speak at the CRUK Manchester Institute.
Oct. 2021 First annual Mansfeld/Zierhut workshop held! Read more here!
Oct. 2021 Welcome to the lab, Lauren Davies!
11 Oct. 2021 Christian to speak at Vienna University.
Sept. 2021 Welcome to the lab, Federico Tidu and Vicente Lebrec!
2 Sept. 2021 Christian to speak at the Social DNAing seminar series.
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.
26 Feb. 2021 Christian awarded a CRUK career development fellowhsip.
11 Nov. 2020 Christian to speak at Oxford University.
30 Oct. 2020 Christian to speak at SUNY Binghamton.
ZierhutLab
Laboratory of Genome Stability and Innate Immunity