About EpiFlaMe P07:
Little is known about inflammatory memory and innate immunity in the liver. Therefore, P07 will break new ground in determining molecular mechanisms of inflammatory memory and assessing its consequences. P07 will provide epigenetic and transcriptional signatures in response to bacterial infection or in response to fatty liver-inducing metabolic stress, define molecular regulators of inflammatory memory in liver epithelial cells, and assess consequences of inflammatory memory on the defense of bacterial infection and liver tumor formation.

Specifically, we will analyze how bacterial infections and metabolic stress induce inflammatory memory in the liver. We will use spatially resolved methods such as spatial transcriptomics and spatial metabolomics to specifically analyze spatial segregation of inflammatory memory in the liver. By using genetic models of hepatocarcinogenesis we will investigate how inflammatory memory in hepatocytes cooperates with oncogenes frequently mutated in human liver cancer. In this context we will also assess if metabolic stress-induced memory is transmitted in utero. Using CRISPR screens we will identify key regulators of inflammatory memory in liver epithelial cells and consequently if pharmacological inhibition of these factors prevents predisposition to liver cancer formation.

Keywords: Cancer, Immunology, inflammation, infection