Topics 8 : Sinusoidal and ECM remodelling in liver diseases

Presentation of research topic 

Liver diseases represent a major and growing burden on human health, with increasing incidence driven by chronic injury, metabolic disorders, and biliary pathologies. These diseases are characterized by progressive alterations in liver architecture, including fibrosis, vascular remodeling, and impaired regeneration, ultimately leading to organ failure.
The liver is a highly organized and dynamic tissue in which multiple cell types—hepatocytes, cholangiocytes, and non-parenchymal cells such as sinusoidal endothelial cells—interact within a complex microenvironment. In chronic liver disease, this microenvironment is profoundly altered, with major changes in extracellular matrix (ECM) composition, mechanical properties, and vascular organization. These alterations disrupt normal cellular functions and promote pathological epithelial plasticity.
Team 8 – Sinusoidal Remodeling and ECM Biology in Liver Disease aims to understand how these microenvironmental changes control liver cell behavior. Our research focuses on two complementary aspects. First, we investigate how vascular remodeling, particularly at the level of liver sinusoids and endothelial cells, shapes liver architecture and impacts regeneration. Second, we study how ECM composition and mechanics regulate cholangiocyte plasticity through nuclear mechanotransduction and chromatin organization.
By combining advanced 3D culture systems, high-resolution imaging, and multi-omics approaches, including spatial transcriptomics, we dissect how biochemical and mechanical signals from the microenvironment are integrated at the cellular and nuclear levels to control cell fate.
Through this work, we aim to uncover the fundamental mechanisms driving liver disease progression and regeneration, with the ultimate goal of identifying new therapeutic strategies targeting the microenvironment to restore liver function.

Keywords

Liver regeneration; Extracellular matrix; Sinusoidal remodeling; Cholangiocytes; Epithelial plasticity; liver microenvironment