Glucocorticoïde receptor-gestuurde heterodimeervorming onder fysiologische en pathofysiologische omstandigheden

01-10-2021 → 30-09-2025
Gewestelijke en gemeenschapsmiddelen: Bijzonder Onderzoeksfonds
  • Medical and health sciences
    • Proteins
    • Medical transcriptomics
    • Endocrinology
glucocorticoïde receptor eiwit-eiwit interactie

Nuclear receptors are intracellular proteins that can function as transcription factors. Many researchers have contributed valuable work to understand how every activated nuclear receptor works by itself inside a given target cell. However, relatively little is known about how two given nuclear receptors with partially overlapping functions can “crosstalk”, i.e. how they cooperate with each other or how they can antagonize each other’s actions. The novel research niche of unconventional nuclear receptor heterodimers is increasingly attracting attention because of its high potential to innovate future drug development strategies. In this context, we aim to understand the fundamental role of glucocorticoid receptor (GR)-centered heterodimer formation under particular physiological and pathophysiological conditions within selected GR target cells. Our approach includes 1) a study of how different ligands and different cell states strengthen or inhibit endogenous nuclear receptor heterodimer formation 2) dedicated bio-assay development 3) use of original in-house tools to study heterodimer impact on nuclear receptor target gene/protein expression and functioning.