Christian Kanstrup Holm, Associate Professor, Aarhus University Department of Biomedicine, Denmark
Christian Kanstrup Holm received his PhD in December 2009 from Faculty of Health Sciences at Aarhus University. Christian completed his postdoc work in the laboratory of professor Søren R. Paludan, also at Aarhus University. This work was focused on new DNA independent mechanism for the activation of the adaptor protein STING by infection with enveloped viruses. Christian started his own research group in December 2014 and is currently focusing on regulatory mechanisms of cellular innate immune responses to infection. His work is based on in vivo models for viral and bacterial infection supported by cellular in vitro work.
The perspective of Christians focus is to exploit built-in regulatory mechanisms of the immune system to dampen immunopathology in infectious as well as in chronic inflammatory diseases.
Abstract from Young Investigator Award’s Session Presentation at Cytokine 2017 in Kanazawa:
The adaptor molecule STING (stimulator of interferon genes) is central to production of type I IFN in response to infection with viruses – in particular DNA viruses. During infection, viral DNA bind the cytosolic DNA sensor and enzyme cGAS, which in response hereto produces the cyclic di-nucleotide cGAMP. Binding of cGAMP to STING leads to STING dimerization and recruitment of the kinase TBK1 and subsequent activation of the transcription factor IRF3 by phosphorylation. infections.Nitro-fatty acids (NFA) are formed naturally by a non-enzymatic addition of NO or NO2 to unsaturated fatty acids and have previously been reported to reduce inflammation in models of heart ischemia.Here, we demonstrate for the first time that NFAs are formed in response to infection with virus. Further, that NFAs can reduce production of type I IFN in response to herpes simplex virus and to stimulation with the STING agonist cGAMP and dsDNA by covalently modifying STING by nitro-alkylation.
NFA hereby represent a novel mechanism to regulate IFN responses by targeting the central adaptor molecule STING.