Coregulators, epigenomes and metaflammation
Our research attempts to better understand how alterations of the epigenome control metaflammation, i.e. inflammation in the context of metabolic diseases such as obesity, type 2 diabetes, fatty liver disease and atherosclerosis. Thereby, we hope to identify novel epigenomic targets and chromatin-based strategies for future prevention and treatment of these diseases.
Epigenome alterations linked to gene expression are fundamental reprogramming processes of the chromatin landscape that are associated with diseases. However, the underlying regulatory mechanisms, the critical components, and the causal relationship of these associations are currently poorly defined. We address these issues with an emphasis on coregulators, proteins that modify chromatin and cooperate with transcription factors. Our search for candidates involved in metaflammation revealed a key role of a fundamental corepressor complex linked to histone deacetylation and demethylation. We suspect that inappropriate expression and function of the complex triggers epigenomic reprogramming and thereby enhances the susceptibility to develop inflammatory disturbances, insulin resistance and type 2 diabetes. To dissect the underlying mechanisms, we apply a multidisciplinary approach including conditional knockout mice, genomic and epigenomic profiling, and translational studies.