Functional genomics approach to understanding sepsis heterogeneity

    Research output: ThesisThesis fully internal (DIV)

    446 Downloads (Pure)

    Abstract

    Every day, we are exposed to bacteria, fungi and viruses present in the environment. However, this exposure usually does not make us sick, thanks to the protection of our immune system. Normally, the responses of the immune system are regulated such that the host body does not get harmed. However, in the case of blood infection, or sepsis, the over-worked immune system can cause life-threatening damage to various organs. Every year, there are more than 31 million cases of sepsis globally, with mortality rates of 17-26%. Sadly, we still do not know why patients have such a large diversity of symptoms and organ failure. The differences in symptoms between patients can be explained by the nature of the pathogens and the human host susceptibility, but the mechanisms involved remain elusive. Therefore, in this thesis, we aim to enhance our understanding of sepsis heterogeneity by applying a functional genomics approach. In chapter 1, we discuss the recent advances on the underlying mechanisms of organ failure in sepsis, focusing on the responses of the endothelial cells in blood vessels. In chapter 2 and 3, we explored how genetic differences between individuals can predispose them to sepsis. In chapter 4, we further delineated the interaction between the white blood cells and endothelial cells in response to sepsis-inducing pathogens. Altogether, our work highlights the important role of endothelial function, together with the immune system, in sepsis pathogenesis.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Wijmenga, Cisca, Supervisor
    • Magadi Gopalaiah, Vinod Kumar, Co-supervisor
    • Moser, Jill, Co-supervisor
    Award date16-Oct-2019
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-034-2095-0
    Electronic ISBNs978-94-034-2094-3
    DOIs
    Publication statusPublished - 2019

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