Within the group of Hans Jonker, we seek a Postdoc to investigate the role of fibroblast growth factor signaling in the development and treatment of NAFLD. We offer a challenging project in a well-organized, international, and high-profile research group within the University Medical Center Groningen.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and one of the most serious pathologies associated with obesity, yet there is still no approved pharmacologic treatment option. Several fibroblast growth factor family members, including FGF1, FGF19, and FGF21, have been shown to regulate hepatic lipid metabolism by targeting their cognate receptor systems consisting of FGF receptors and the co-receptor beta-klotho. Alterations in FGF signaling may therefore contribute to the development of NAFLD. Although various clinical trials are currently investigating the safety and efficacy of FGF-mimetics in the treatment of NAFLD, the underlying mechanisms through which modulation of FGFR activity controls hepatic lipid metabolism remain largely elusive.
This project aims to define the molecular mechanism by which activation or inhibition of FGFR signaling pathways affects hepatic lipid metabolism and how this can contribute to the development or treatment of NAFLD. The following key objectives will be addressed: (i) to study how pharmacological and genetic modulation of FGFR activity affect hepatic lipid metabolism; (ii) determine factors that control the transcriptional regulation of FGFR pathway components and how this impacts the FGF-based treatment of NAFLD, and (iii) mapping of the FGFR signaling machinery in tissue biopsies of NAFLD patients.
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