How DNA Damage Response contributes to Liver Metabolic Disorders – DNAFAT

Non-Alcoholic Fatty Liver Disease (NAFLD) is a major public health concern. Alarmingly, steatosis (NAFL) progresses pejoratively to Non-Alcoholic Steatohepatitis (NASH), which is considered as a growing worldwide epidemic threat, due to the absence of treatment. DNA-FAT consortium identified for the first time how DNA Damage Response triggers the cGAS-STING pathway in hepatocytes linking DNA lesions, metabolism and immunosurveillance. The goal of DNA-FAT project is now to determine how DNA Damage Response contributes to Liver Metabolic Disorders. Our project involves efficient teamwork, sharing unique tools, techniques and scientific expertise and will be dedicated to: Obj. 1: - Monitor the outcome of DNA lesions accumulation in fatty hepatocytes during NAFLD. Obj. 2: - Decipher the role of DDR genes in metabolic reprogramming during NAFLD, Obj. 3: - Unravel the role of STING/cGAS pathway in the inflammatory response during NAFLD. Obj. 4: - Perform a translational analysis in human NAFLD. DNA-FAT project should represent an important step towards that will allow the identification of novel therapeutic candidates to prevent the NAFLD progression.