Cancer Immunology:
Hedgehog signalling in the Immune System
Hedgehog is an ancient cell-cell signal transduction pathway known to control embryonic development and adult tissue maintenance. In vertebrates the pathway is tied to the primary cilium – a hairlike signalling organelle protruding from nearly every cell in the body.
The cells of the immune system do not form primary cilia. Instead, they form immune synapses, that are morphologically very similar to the primary cilium, to communicate with each other and the environment.
We have previously shown that Hedgehog is activated downstream of the T cell receptor at the immune synapse of CD8 T cells and controls killing in vitro. We now want to understand how the diverse cells of the immune system differentially exploit Hedgehog signalling in vivo in the context of cancer, infection, and autoimmunity.
The laboratory has generated unique mouse models and reagents to investigate the role of Hedgehog signalling in various immune cell subsets and is running a clinical trial investigating the role of Hh-mutations and Hedgehog inhibitor treatment in cancer patients.
We aim to characterise the distinctive mechanistic features of immune Hedgehog signalling with the long-term goal to modulate Hh signalling in immune cells to improve immune responses in the context of cancer, infection, autoimmunity and vaccination.
Selected publications
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Cell-autonomous Hedgehog signaling controls Th17 polarization and pathogenicity
E-pub date: 14 Jul 2022Journal name: Nat Commun
Non-canonical Hedgehog signaling through L-type voltage gated Ca2+ channels controls CD8+ T cell killing
E-pub date: 1 Mar 2021Journal name:
LGR5 targeting molecules as therapeutic agents for multiple cancer types
E-pub date: 1 Aug 2022Journal name:
IL-7-dependent compositional changes within the γδ T cell pool in lymph nodes during ageing lead to an unbalanced anti-tumour response.
E-pub date: 31 Aug 2019Journal name: EMBO Rep
Hedgehog signaling controls T cell killing at the immunological synapse.
E-pub date: 6 Dec 2013Journal name: Science
Funding