Role of stroma-regulated epithelial miRNAs and ZEB2 in pancreatic carcinogenesis

• Applicant: Professor Dr. Guido von Figura
• Subject Area: Gastroenterology
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 192431918

Pancreatic ductal adenocarcinoma is characterized by a high mortality, which is due to a diagnosis in often incurable stages and a lack of effective therapies. There is a desperate need to better understand the molecular basis of pancreatic carcinogenesis in order to develop efficient diagnostic and therapeutic tools.In the past years, a major progress in understanding the molecular basis of this cancer has been made. Mouse models have been developed that harbor genetic mutations that are also common in human pancreatic cancer (e.g. mutations in Kras, p53, INK4a). These mouse models closely resemble human pancreatic carcinogenesis.miRNAs are posttranscriptional regulators of gene expression and play a fundamental role for important cellular processes and also carcinogenesis. Recently, it has been shown that the stroma-tumor interaction leads to a dysregulation of epithelial miRNAs. However, the functional role of these miRNAs for carcinogenesis is not yet clear. This research project focuses on (a) characterization of the role of stroma-regulated epithelial miRNAs and ZEB2 in regulating growth and stem cell properties of pancreatic cancer cells, and (b) generation of a tumor mouse model with genetic alterations in miRNAs and ZEB2 to address their functional role for carcinogenesis in vivo. To understand the functional role of miRNAs for pancreatic carcinogenesis could provide new diagnostic and therapeutic tools to combat this fatal disease.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Matthias Hebrok, Ph.D.