Shivani Singh

PhD Student

Verena Keitel-Anselmino

Project Leader

Biliary diseases are characterized by complex interactions between various liver cell types, including hepatocytes, cholangiocytes, and immune cells, mediated through intricate intra- and intercellular signalling pathways. Understanding these communication networks is essential for deciphering disease mechanisms and identifying effective therapeutic targets. Traditional models often fail to capture the complexity of cellular crosstalk and the dynamic microenvironment of the biliary system, limiting their utility for understanding disease progression and testing therapies. This highlights the need for more sophisticated multicellular organoid models and patient-specific systems to enable personalized medicine.

This study focuses on the development and optimization of advanced in vitro models to investigate cellular crosstalk in biliary diseases. Key approaches include:

1. Organoid Systems: Advanced organoid models, such as tumoroids and spheroids, will be utilized to study cholangiopathies and bile duct remodelling. These models aim to incorporate multiple cell types, including immune cells, fibroblasts, and endothelial cells, to better replicate the complex interactions within the biliary system.
2. Co-Culture Systems in Biliary Disease Modelling: Co-culture systems will be employed to replicate the dynamic liver microenvironment by integrating various liver cell types, such as hepatocytes, cholangiocytes, immune cells, fibroblasts, and endothelial cell. These systems provide a physiologically relevant platform to study intercellular signalling and interactions critical to biliary disease pathogenesis, including inflammation and fibrosis development as well as bile acid regulatory networks.
3. Multi-Omics Approaches: RNA sequencing data from (P11-2) will be used to identify key signalling pathways within biliary epithelial cells. By integrating transcriptomic data with proteomic (Multiplex; CSP-5) and epigenomic analyses (Cooperation P12-2, P12-3), these approaches will provide a comprehensive understanding of the cellular and molecular mechanisms underlying disease pathology and help identify potential therapeutic targets. 

The advanced models developed in this study will enhance our understanding of biliary disease pathophysiology and provide valuable platforms for drug screening and the development of targeted therapies. This work underscores the importance of precise and physiologically relevant models in advancing biliary disease research and lays a solid foundation for future translational studies.

Establishment of in vitro liver models using organoids, spheroids, and co-culture systems to study cellular crosstalk in normal and diseased conditions. Functional validation is performed through RNA sequencing, immunohistochemistry, immunofluorescence, and proteomics.