Grant: Team Grant: Epigenomics of Complex Diseases

Obesity is a leading cause of death worldwide affecting over 500 million individuals' worldwide, figures that have nearly doubled since 1980. While the disease is an important risk factor for the development of type 2 diabetes (T2D) we still do not know why not all obese patients develop T2D. Likewise, no clear explanations exist that can fully explain why some but not all individuals treated for obesity by bariatric surgery recover from T2D. Genetic influences are important but confer only a modest risk indicating key role of environmental factors acting either alone or together with genetic factors. To this end, we aim to take advantage of the ability of modern, high-throughput DNA technologies to characterize millions of not only genetic variants but also environmental influences on gene function and disease risk that are not caused by an indivuals' DNA sequence. We will apply these tools in adipose and liver cells derived from both clinical cohorts and pre-clinical models targeting these metabolic conditions. More specifically, we will combine work in disease and population-based study materials with experimental animal models (rats and mice) that mimic novel and immediately relevant aspects of human metabolic disease pathology, ruling out genetic variables and thus dramatically strengthening statistical power for detecting relevant changes. Results from the joint investigations in these well-established models of obesity and T2D in mice and rats have strong translational potentials into human diseases. Finally, with the access to unique longitudinal studies following bariatric surgery patient over time we will also be able to address whether identified environmental marks can be used to predict bariatric surgery outcomes such as T2D recovery - breakthroughs that would have great potential for the development of new treatment strategies.