Investigation of therapeutic targets of altered Hippo-signalling in liver cancer

• Applicant: Professor Dr. Darjus-Felix Tschaharganeh
• Subject Area: Pathology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 215611262

Hepatocellular carcinoma (HCC) is the fifth common cancer worldwide with an increasing incidence. To date there only exist a few therapeutic options for patients in advanced tumor stages despite intensive research. The molecular basis of HCC is complex and involves several signalling pathways which contribute to the progression of HCC. The Hippo-signalling pathway is a highly conserved signalling pathway which is involved in organ size control and organ homeostasis. Current publications could show that alteration of Hippo-signalling has an important function in the progression of HCC. The aim of this project is to investigate the contribution of the different Hippo-signalling pathway members to HCC progression by using an unique HCC-mosaic mouse in combination with in vivo RNA-interference (RNAi). Moreover, this project will identify therapeutic targets of altered Hippo-signalling by using two different strategies. Firstly, direct target genes of Hippo-signalling will be identified by gene expression analyses and genomic analyses and will be validated via RNAi. Secondly, Hippo-specific, synthetic lethal genes will be identified by using a RNAi-library containing druggable genes in combination with a currently discovered RNAi-based system for negative selection. Lastly, the data will be validated in human samples. These strategies will help to reach effective therapies for cancer with altered Hippo-signalling.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Scott Lowe, Ph.D.