Novo Nordisk Fonden - Hepatic dysfunction in cancer cachexia

Cancer cachexia is a devastating multi‐factorial condition characterized by massive loss of adipose tissue and skeletal muscle mass, which is believed to be the direct cause of up to 30% of cancer‐related deaths in humans. Despite frequently documented steatohepatitis in experimental and human cancer cachexia, and its central role in other metabolic diseases, the liver has received little attention in this context. This project is aimed at unequivocally demonstrating the importance of hepatic dysfunction for energy wasting in cancer cachexia, and more specifically defining the role of systemic insulin resistance induced by the cachexiainduced transcriptional repressor TSC22D4 herein. Concurrently, new state-of-the-art experimental platforms for hepatocyte-specific in situ genomic and transcriptomic profiling will be implemented and applied to the genomewide characterization of the genomic and transcriptional reprogramming of hepatocyte function in cancer cachexia. We expect the proposed project to challenge the current perception of cancer cachexia as a condition of the adipose and muscle tissues, which given the high potential of the liver for uptake of drugs and particularly siRNA-based therapeutics may outline possibilities for improved therapeutic intervention in cancer cachexia. The majority of the project will take place in the group of Prof. Stephan Herzig, Institute of Diabetes and Cancer (IDC), Helmholz Zentrum Munich (HMGU). Through research-based training in methodologies for genetic manipulation and phenotyping of mice and interaction and collaboration with other research groups at HMGU, the outlined project will facilitate my transition from postdoctoral to independent researcher. The developed methodologies will serve as a natural platform to build future collaborations and projects both at HMGU and at the Department of Biochemistry and Molecular Biology (BMB) upon my return to University of Southern Denmark (SDU) for the last year.