Cel 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. Dziedzina nauki medical and health sciencesclinical medicineoncologyliver cancernatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicinehepatologymedical and health sciencesbasic medicinepharmacology and pharmacyadverse drug reactionsnatural sciencesbiological sciencesgeneticsepigenetics Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2013-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Zaproszenie do składania wniosków FP7-PEOPLE-2013-IEF Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-IEF - Intra-European Fellowships (IEF) Koordynator KAROLINSKA INSTITUTET Wkład UE € 206 350,80 Adres Nobels Vag 5 17177 Stockholm Szwecja Zobacz na mapie Region Östra Sverige Stockholm Stockholms län Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Eva Gipperth (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych