The decline in cost for high throughput methodologies such as next generation sequencing (NGS) and powerful computing enables researcher to obtain genetic information from the entire genome. The availability of such methodologies requires a high sensitivity to ethical aspects. Also several scientific issues are remaining. Thus, before such methodologies can enter clinical practice, experiences with NGS in clinical settings have to be acquired. We choose to investigate on the genetics of diseases employing family sequencing. Family sequencing offers significant benefits over sequencing cohorts of unrelated individuals, because it allows a more accurate construction of the inheritance of genetic information on every piece of the chromosomes.

University of Luxembourg and the Luxembourg National Research Fund (FNR)

We are interested in studying dynamic changes in the microbiome of healthy individuals and patients. Understanding microbiome-related consequences in health and disease opens a huge opportunity for designing personalised diagnostics and treatments. Together with collaborators at the LCSB and the hospitals we focus on microbiome-dependent changes in conditions such as malignant diseases or inflammation. In the SMART (saliva microbiome and radiation therapy) clinical study, we are investigating the changes in the saliva microbiome of head and neck cancer patients undergoing radiation therapy. The microbiome signatures are expected to facilitate understanding the severity of side effects as well as to discover novel and individualized treatment options. In the MICROH-Liver project, using 3D liver models, we will be investigating the role of microbial metabolites in glucose and lipid homeostasis.

University of Würzburg

An ongoing effort relies in the detection of candidate genes for endocrine disorders, both in familial or sporadic settings. Together with the University of Wuerzburg we sequence a series of adrenal tumors and the corresponding leukocyte DNA to find the causing mutations for the onset of sporadic Cushing´s disease. Conn syndrome is another adrenal disease. It is an aldosterone-producing adenoma which may result in hypertension, muscle cramps and weaknesses as well as chronic headaches. With our partners from Alicante and Munich, we have identified a family with a suspected inherited genetic cause of Conn syndrome. We have sequenced the family to investigate the genetic causes. We are validating the results with a CRISPR/Cas gene-edited in vitro model. The results of the project will help identify modifiers of the disease and discover new drug targets in aldosterone regulation.

Charité Berlin, University of Magdeburg, the Saarland University Medical Center in Homburg/Saar and the University of Lorraine in Nancy

Metabolic disorders include obesity, insulin resistance, diabetes and fatty liver diseases. Several clinical and experimental projects are ongoing in collaboration with several clinical partners such as the University of Magdeburg, the Saarland University Medical Center in Homburg/Saar and the University of Lorraine in Nancy. Together with Charité Berlin, we will be investigating the effects of calorie restriction / fasting on inflammation and especially Rheumatoid arthritis.

This research has received funding from the European Union’s Seventh Framework Programme.

Inflammatory vascular disease such as atherosclerosis or vascular inflammation affect many subjects of the world population. Since vascular diseases represents a lipid-driven inflammation the pathophysiology requires a wiring of metabolism and immune system. IRG1 is a macrophage specific gene characteristic for immune system activation and is induced by bacterial stimuli as well as oxLDL. The IRG-1 dependent production of the substrate itaconic acid (ITA) directly interferes with cellular tricarboxylic cycle (TCA) metabolism. IRG-1 also mediates the production of reactive oxygen species (ROS) in macrophages. These data suggest that IRG-1 links innate immune activation with metabolism. We aim to characterize the role if IRG-1 in inflammatory vascular disease in vivo and in vitro. This project aims at defining a novel player as potential target mechanism for inflammatory processes in the vasculature. Another molecule of interest is β3 integrin, which is shown to be involved in various pathophysiologic processes such as cancer/neoangiogenesis, platelet aggregation, inflammation, bone resorption, and vascular disease. We further elucidate the role of β3 integrin in a cell-specific fashion using Cre/Lox technology in vivo, in conditional β3 deletion in vitro models and in silico utilising high-throughput data acquisition followed by modelling of the signalling pathway based on the experimental data.

Charité Berlin, Centre Hospitalier Emile Mayrich, Department of Life Sciences and Medicine, Luxembourg Institute of Health and the Integrated Biobank of Luxembourg

In collaboration with Charité Berlin providing a huge cohort of tinnitus and comorbid disorders, we are investigating the epigenome and metabolome of these patients to discover mechanistic causative factors to stratify the study population. As preparatory work, we will be collaborating with the Department of Life Sciences and Medicine, the Luxembourg Institute of Health and the Integrated Biobank of Luxembourg for the development of analytic methods. In another study, PERMENTI, we are investigating the psychological effects, especially depression, caused by inflammatory bowel disease (IBD). Together with the Centre Hospitalier Emile Mayrich in Esch-sur-Alzette, we will investigate the effects of immunological factors in IBD patients on the mental well-being of the patients.

In addition to the research projects described above, Prof. Jochen Schneider also holds various functions impacting the biomedical landscape in Luxembourg and beyond by:

• Serving as deputy director for the first year of medical education of students at the University of Luxembourg
• Being a member of the Comite Nationale d´Ethique de Recherche de Luxembourg (CNER) and the Vice-Chair of the Ethics Review Board (ERP) of the University of Luxembourg
• Being a member of the Animal Experimentation Ethics Committee (AEEC)