Circadian desynchronization and epigenetic alteration crosstalk on the development and resolution of metabolic dysfunction-associated steatohepatitis (B02)

• Subject Area: Gastroenterology ; Endocrinology, Diabetology, Metabolism
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 541063275

Hepatologist Jens Marquardt teams up with chronobiologist Maria Robles, an expert in circadian mass spectrometry-based quantitative proteomics to study the crosstalk between circadian desynchronization and epigenetic alterations in the development and resolution of metabolic dysfunction-associated steatohepatitis (MASH). While a synchronized circadian-epigenetic network is critical for maintaining metabolic homeostasis, the precise circadian- and epigenetic-dependent changes that drive the development and resolution of MASH remain unknown. Using mouse models, ex vivo primary hepatocyte cultures and organoids as well as in a cohort of obese patients with MASH following bariatric surgery and defined lifestyle interventions, the project will investigate how circadian disruption modulates liver DNA methylation and nuclear proteome, and how this depends on a functional circadian clock, DNA methyltransferase 1, and diet.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 418: Foundations of Circadian Medicine
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Heads: Professor Dr. Jens U. Marquardt; Professorin Dr. Maria Robles