Development of a novel in vitro tumorigenesis model to characterize the cellular perturbations induced by the distinct driver mutations in pancreatic adenocarcinoma

• Applicant: Dr. Matthäus Felsenstein, Ph.D.
• Subject Area: General and Visceral Surgery
• Term: from 2017 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 377963688

Pancreas adenocarcinoma is one of the deadliest malignancies and increasing incidences urge for earlier detection and improved therapies. It arises from pancreatic precursor lesions mainly from duct epithelial cells by accumulating genetic alterations (KRAS, CDKN2A, TP53, SMAD4). Despite best efforts, no conclusive cellular in vitro carcinogenesis model is currently available. A general issue is the derivation of non-neoplastic epithelial cells and their limited propagation in vitro. E6/E7 immortalized Human Pancreatic Duct Epithelial cells (HPDE) are the only available source, but already harbor significant perturbations in cell cycle checkpoints. A less aggressive option for cellular immortalization will be applied (hTERT), which could help to improve the analysis of earlier genomic events in pancreatic cancer. With the innovative field of CRISPR/Cas9 genome engineering, genetic alterations can be accurately installed and tumor progression models implemented. Thus the central goal of this study will be the application of a convincing in vitro carcinogenesis model using a new pancreatic duct cell line in conjunction with modern genomic engineering techniques.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Laura Delong Wood, Ph.D.