Hepatic organization and functions
Division Of Basic Sciences - Nci
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Abstract
We aim to identify the mechanisms that maintain cellular heterogeneity and spatial compartments in liver physiology and gain insights into how these mechanisms are disrupted in liver disease and cancer. We use diet-induced metabolic stress either through overnight (ON) fasting or western diet (WD) to model the onset of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), a major precursor for liver cancer, in mice. Additionally, primary hepatocellular carcinoma (HCC) models are utilized to investigate the early stages of tumorigenesis. In complementary studies, biopsies from patients shed light on zonation in the human liver. We apply cutting-edge technologies, including Intravital microscopy (IVM) and volumetric electron Microscopy (vEM), combined with in-house developed cell isolation and AI-guided image analysis. The knowledge gained will lead to a better understanding of liver physiology, approaches for tumor classification, prevention, and, ultimately, novel therapy approaches.
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