Multi-Omics and Spatial Analyses of Immune-metabolic Crosstalk in Steatotic Liver Diseases (MOSAIC-SLD)

• Applicant: Dr. Hanyang Liu
• Subject Area: Gastroenterology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 576404128

The liver is a complex organ responsible for vital metabolic functions, including processing nutrients, detoxifying harmful substances, and regulating energy. These functions are not evenly distributed but vary across specific zones of the liver lobule. This “zonal heterogeneity” plays an essential role in maintaining liver health. However, in steatotic liver diseases (SLD), including metabolic dysfunction-associated steatotic liver disease (MASLD), this functional organization becomes disrupted, especially under the influence of immune system activity. Among the immune cells involved, liver macrophages (including Kupffer cells and monocyte-derived macrophages) are known to actively communicate with hepatocytes (the main liver cells) and influence their functions during disease. Yet, it remains poorly understood how this cellular crosstalk contributes to disease progression and treatment response, especially in specific regions of the liver. This project, building on the applicant’s prior research, aims to decode how interactions between hepatocytes and macrophages drive liver injury, inflammation, and fibrosis in SLD. The study will pursue three main objectives: 1. Mapping liver regions in health and disease: Using advanced techniques such as single-cell and spatial transcriptomics, the project will map how hepatocytes behave differently across various liver zones, particularly focusing on their gene activity and metabolic functions during disease. 2. Identifying regulators of disease-prone hepatocytes: The study will explore why certain hepatocytes, particularly those in the mid-lobular region, are more vulnerable in SLD. By identifying key regulatory genes and pathways, it will uncover what drives their dysfunction. 3. Understanding immune-metabolic interactions: Using a combination of animal models and cutting-edge liver-on-a-chip systems, the project will study how diseased hepatocytes affect macrophage behavior and immune responses, and how they respond to treatment. By clarifying how hepatocytes and macrophages interact across different zones of the liver during disease, this research will provide novel mechanistic insights and open new paths to more precise and targeted therapies for SLD.

• DFG Programme: Position