- Nuclear receptors and their co-factors in hematological and inflammation-driven disorders
C.J.M. de Vries
V. de Waard
- Award date
- 6 July 2018
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
Nuclear receptors are a class of ligand-activated transcription factors that regulate the expression of genes involved in all aspects of cellular biology. The nuclear receptors Nur77 and liver X receptor (LXR) are two well-established regulators of inflammation and metabolism that play important roles in the pathogenesis of diseases driven by excessive inflammation and dysregulated metabolism, such as atherosclerosis. This thesis describes new ways in which the activity of Nur77 and LXR is regulated and how they, in turn, can regulate cellular metabolism, inflammatory responses, and immune cell differentiation. The key findings of this thesis include the identification of two novel coregulatory proteins that enhance Nur77 and LXR activity, the genome-wide profiling of Nur77 binding sites and target genes in macrophages, the identification of Nur77 as an important factor in the metabolic switch of macrophages upon inflammatory stimulation, and the characterization of differences in hematological phenotypes between two distinct Nur77-deficient mouse models.
Thesis (complete) (Embargo up to and including 6 July 2020)
Chapter 5: Nuclear receptor Nur77 limits the macrophage inflammatory response by reprogramming mitochondrial metabolism (Embargo up to and including 6 January 2019)
Chapter 8: Nuclear receptor Nur77 variants solely comprising the aminoterminal domain activate HIF-1α and affect bone marrow homeostasis in mouse and man (Embargo up to and including 6 January 2019)
Chapter 9: Nuclear receptor Nur77 and transcription factor YY1 synergistically increase mitochondrial content and activity in macrophages (Embargo up to and including 6 July 2020)
Chapter 11: General discussion (Embargo up to and including 6 July 2020)
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