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Fatty Liver Disease and Liver Fibrosis Research Team

Principal Investigator: Yang Zhang and Jing Zhang

The Fatty Liver Disease and Liver Fibrosis Research Team brings together the Beijing Institute of Hepatology, with    its expertise in basic research, and Beijing You’an Hospital, Capital Medical University, which provides    comprehensive clinical care and research. Operating within a basic-clinical-translational framework, the team    investigates the mechanisms driving Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) across its    progression, from hepatic steatosis through metabolic dysfunction-associated steatohepatitis (MASH) to liver    fibrosis, with the ultimate goal of developing targeted, precision interventions for clinical applications.

Main Research Directions:

1. Mechanisms of the Cascade Progression of MASLD Driven by Imbalance in the Energy-Lipid Metabolic Network

We focus on key elements linking the energy metabolism network and lipid homeostasis system. By examining organelle    interactions, activation of metabolic sensing pathways, and toxic accumulation of metabolic intermediates, we aim to    elucidate the cascade mechanisms that drive the transition from energy surplus to lipid homeostasis collapse. In    particular, we seek to identify critical regulators governing progression from steatosis to inflammation and    fibrosis, thereby establishing an integrated paradigm of "Metabolic Stress Sensing-Organelle Communication    Remodeling-Metabolic Flux Redirection."

2. Molecular Network Remodeling and Regulatory Mechanisms of Genetic Susceptibility in MASLD

This research direction explores the core mechanisms by which genetic factors confer susceptibility to MASLD. We aim    to construct a molecular susceptibility framework, clarifying how hereditary alterations in key lipid metabolism    genes, imbalances in glucose and lipid metabolism, and defects in organelle interaction regulation contribute to    disease risk. Furthermore, we seek to elucidate the regulatory networks through which gene-environment interactions    synergistically drive MASLD progression, providing novel theoretical foundations and research paradigms for    understanding the pathogenesis of hereditary MASLD.

3. Comorbidity Mechanisms and Molecular Regulatory Networks of MASLD, Obesity, and Diabetes

MASLD, obesity, and type 2 diabetes mellitus (T2DM) share core pathological features, including insulin resistance,    chronic inflammation, and lipotoxic stress. Our team investigates the molecular regulatory networks that govern    their interactions and the spatiotemporal dynamics of multi-organ metabolic imbalance. We aim to elucidate key    mechanisms, including inter-organ transmission of lipotoxic signals, MASLD-specific regulatory hubs,    microenvironmental dysregulation, cellular heterogeneity, and microbiome-host co-metabolism. The ultimate goal is to    identify novel coordinated regulatory targets and develop multidimensional intervention strategies for this    comorbidity network.