Objective Inter-individual differences in reaction to drugs and pharmacological treatments can cause severe adverse drug reactions (ADRs) and are a common reason of withdrawal of drugs from the market. ADRs are as costly for society as treatment itself and are a major cause of hospitalizations and deaths. Genetic polymorphisms in genes encoding enzymes involved in drug metabolism can only explain a small subset of the inter-individual differences in response to pharmacological treatment. Recently, the host lab identified DNA hydroxymethylation (5hmC) as a stable and abundant epigenetic modification that influences liver function and development. The project proposed here aims at the elucidation of epigenetic polymorphisms that impact on the expression of hepatic genes involved in metabolism and disease with particular focus on 5hmC. To this end, a multidisciplinary approach is employed using bioinformatic analyses of Next Generation Sequencing data and functional testing of identified sites in 3D integrated liver cultures and iPS derived hepatocytes. The identification of DNA elements whose epigenetic status influences liver gene expression and drug response is directly translated to clinical applications as it will improve pharmacological treatment by tailoring to the epigenomic information of the individual patient.Additionally, the identification of epigenetic polymorphisms in obesity and liver diseases such as cholestatic disease, liver cancer metastases, steatosis or cirrhosis promises a better understanding of these common detrimental liver conditions and can contribute to the design of novel therapeutic strategies.Furthermore, differentially modified DNA elements will be used as hepatic biomarkers for the non-invasive blood-based detection of liver diseases. Fields of science medical and health sciencesclinical medicineoncologyliver cancernatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicinehepatologymedical and health sciencesbasic medicinepharmacology and pharmacyadverse drug reactionsnatural sciencesbiological sciencesgeneticsepigenetics Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2013-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2013-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator KAROLINSKA INSTITUTET EU contribution € 206 350,80 Address Nobels Vag 5 17177 Stockholm Sweden See on map Region Östra Sverige Stockholm Stockholms län Activity type Higher or Secondary Education Establishments Administrative Contact Eva Gipperth (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
