The general theme of my research is to elucidate the molecular regulation of metabolic processes with a focus on (chole)sterol metabolism. In this respect, my work is multidisciplinary extending beyond the physiology of metabolism to a number of relevant biological processes such as inflammation, regeneration and ageing as well as their related outcomes such as atherosclerosis. Central to my research are the relevance for human disease and the in vivo aspect, mostly comprising characterization of physiological processes with the help of mouse models. In our translational work we test concepts generated in animal models also in human patients or take a vice versa approach to understand the mechanistic basis of clinical observations with the help of animal or cell culture models.

Specifically, the following topics are the current focus of my work.

1. HDL function and regulation of reverse cholesterol transport.

For the in vitro part assays were developed to determine the efflux capacity, the anti-oxidative and anti-inflammatory functionality of HDL isolated either from mouse models or human populations. These assays have been validated for a high throughput format. In vivo, using mouse models, we aim to identify key factors impacting reverse cholesterol transport from macrophages to feces using specific knockout or overexpression models as well as pharmacological or surgical interventions.

2. Regulation of biliary as well as non-biliary routes of sterol elimination.

With respect to the biliary route of sterol elimination we aim to identify the lipoprotein sources as well as the intracellular trafficking routes and potential different pools of cholesterol in the liver. Regarding the non-biliary routes of cholesterol elimination I am interested in the still relatively novel pathway of transintestinal cholesterol excretion (TICE) and aspects of its molecular regulation.

3. Epigenetic programming of metabolic and cardiovascular health.

This line of research builds on the hypothesis that we are programmed for health or disease by early life events occurring either in utero or during the early postnatal period. I am interested to characterize specific insults underlying programming as well as the molecular characterization of epigenetic changes determining certain phenotypes. A specific focus is put on the definition of a susceptibility window for programming after birth. Main read-outs are related to cardiometabolic health.

4. Impact of the intestinal microbiota on inflammation, bile acid metabolism and cardiometabolic disease.

Here we make use of the germ-free mouse facility in our animal house. Thus far, we investigate the dependency of metabolic effects of complex carbohydrates on the intestinal microbiota and characterize cholesterol metabolism including reverse cholesterol transport in germ-free models. In addition, we assess, if and how the microbiota impacts epigenetic programming of cardiometabolic disease.