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Content archived on 2024-06-18

Epigenetic mechanisms underlying inter-individual differences in drug response and hepatic disease

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 (EuroSciVoc)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

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FP7-PEOPLE-2013-IEF
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

KAROLINSKA INSTITUTET
EU contribution
€ 206 350,80
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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