Our research focuses on how metabolic changes impact the epigenetic landscape. This is important, as changes in metabolic networks drive dramatic changes in cellular phenotypes and identity. The stark rise in metabolic disorders has given our research further impetus. Through a better understanding of how metabolic disease disrupts the epigenetic landscape, we hope to clinically address a rapidly growing health problem. We address our scientific questions using a multidisciplinary approach integrating metabolomics, epigenomics, transcriptomics, single cell technologies, proteomics, biochemistry and high-end confocal imaging.
Epigenetics
To map the impact of environmental and in particular metabolic changes on the epigenome, we utilize mass spectrometry methodologies to quantify changes in chromatin modifications. Through integration with transcriptomic and high-throughput ChIP-seq analyses, we are able to understand the genomic loci and mechanisms that respond to environmental changes. We confirm the mechanistic links between the metabolic and epigenetic landscapes through Crispr-Cas9 mediated gene deletions.
Metabolism
To understand metabolic changes in genetically modified cells, pre-clinical models and clinical samples, we undertake mass spectrometry-based metabolomics to quantify and map metabolic flux using 13C labelling. Coupled with sea-horse assays and proteomics, we aim to uncover how environmental, genetic and epigenetic influences drive shifts in metabolic flux.
Metabolic Disease
With a rapid rise in the global incidence of metabolic diseases such as obesity and diabetes, our research addresses how metabolic deregulations impacts the epigenetic and transcriptional profile. We achieve this by analyzing pre-clinical models as well as clinical samples from obese and diabetic patients. Together with the Leipzig LIFE Cohort, our research aims to uncover mechanisms that drive the development of co-morbidities associated with a pathological metabolic profile.
Vascular Disease
One common factor associated with virtually all metabolic disorders is the global presence of vascular disease. Utilizing single cell transcriptomic and epigenetic technologies, coupled with confocal and light-sheet imaging, we address how changes in the metabolic environment impact the function, phenotype and transcriptional state of vascular endothelial and mural cells. We undertake these investigations in clinical atherosclerosis samples, pre-clinical models and primary human vascular cells.