Functional Metabolomics

Off target effects of lipid-lowering drugs

Lipid-lowering drugs like statins and fibrates are widely prescribed for the treatment of obesity and cardiovascular related diseases. The desired drug effects are, however, often accompanied by unwanted side effects. Since the molecular mechanisms behind the side effects are not or scarcely known we try to unravel these processes. We analyze the effects of lipid-lowering drugs on different human cell types. By using robust and reliable assays based on human cell culture and metabolite quantification by targeted and non-targeted metabolomics (at the Metabolomics Platform (Link: www.helmholtz-muenchen.de/gac/platforms/metabolomics/overview/index.html)) we can detect global metabolic changes upon drug challenges. The project can thus provide information on the metabolite profile changes induced by drugs of different classes as well as the identification of potential unknown off-targets.

Project lead: Dr. Janina Tokarz

Assay Development for TCA metabolites

The tricarboxylic acid (TCA) cycle is central for the basic metabolism of a cell and an organism. The disturbance of the TCA cycle is thus associated with diverse metabolic diseases. To be able to monitor changes in TCA cycle metabolites in biological samples, we develop and apply a GC/MS based quantification method.

Project lead: Florian Miehle

Effected Pathways in D-Bifunctional Protein deficiency

Multifunctional protein-2 (MFP-2) plays an important role in peroxisomal -oxidation. Deficiency of the enzyme in humans causes a severe developmental syndrome with multiple abnormalities, particularly in the brain. Most of the affected individuals die within the first year of life. There is no report on the metabolite profile nor the pathophysiology and etiology of malfunctions in several organs. To understand the effected pathways of the disease, metabolite profiles of tissues and plasma derived from the MFP-2 knockout mouse (MFP2 KO), partly phenocopying the human disease, are analysed. 

Project lead: Dr. Anna Artati

Detection of early onset of T2D – Development of a diagnostic assay and pathway characterization

Type 2 Diabetes (T2D) is a lifelong, incapacitating disease affecting multiple organs. Presently, T2D cannot be cured but (partially) prevented. A third up to a half of the adult population above age 50 may be in prediabetic state. Prediabetes is defined by impaired fasting glucose and/or impaired glucose tolerance (IGT) and may precede T2D for years. Until now, a repeated “oral glucose tolerance test” (OGTT) is the only golden standard to diagnose IGT, but it demands high efforts in logistics and medical care, is time consuming and costly. It is thus our aim within the framework of the EIT-Health project “DeTec2D” to develop a diagnostic assay which is more efficient than OGTT. 

Project Lead: Florian Miehle

Metabolomics on anti-diabetic drug treated cells

Metformin is the most prescribed anti-diabetic drug and becomes more and more attractive for the treatment of other diseases like cancer. Many modes of action of the drug are already deciphered, but not all are yet known. We apply cell culture techniques combined with omics methods to find new drug effected pathways or pathway connections. 

Project Lead: Florian Miehle