Molecular Endocrinology

Cortisone metabolizing enzymes in humans

A novel cortisone metabolizing enzyme, 20beta-hydroxysteroid dehydrogenase type 2, was recently identified in the model organism zebrafish and some other teleost fish species and was postulated to be involved in cortisone catabolism. The enzyme product was found to be also present in human samples such as urine and plasma, however, the responsible human enzyme is yet unknown. In order to find the respective enzyme and to elucidate novel pathways for cortisone catabolism in humans, we employ different methods in molecular biology, biochemistry, as well as targeted steroidomics (in-house developed targeted metabolomics methods for steroid quantification).

Project Lead: Dr. Janina Tokarz

Development of methods for the quantification of steroids in tissue

The Metabolomics Platform at the GAC offers both commercial as well as in-house developed methods for the quantification of steroids in human or murine body fluids such as plasma (Portfolio of the Platform). However, to be able to quantify not only systemic but also local tissue steroids we develop novel protocols for the steroid extraction from several tissue types

Project Lead: Florian Miehle

Development of selective inhibitors for 17β-HSDs

17β-hydroxysteroid dehydrogenases (17β-HSDs) are important enzymes in steroid and lipid metabolism. Due to their central roles the enzymes are associated with diseases, like breast cancer and endometriosis (17β-HSD1), osteoporosis (17β-HSD2), pseudohermaphroditism (17β-HSD3), prostate cancer (17β-HSD5), D-bifunctional protein deficiency (17β-HSD4, also called MFP-2), Alzheimer disease and MHBD (17β-HSD10), to name some.
In order to develop new treatments for breast cancer, endometriosis and osteoporosis we are testing compounds synthesized by organic chemists or library compounds for their inhibitory potency against the respective target enzymes as well as off-target enzymes (screening assays, kinetics).

Project Lead: Dr. Gabriele Möller

Molecular Mechanisms of Adipogenesis – Mgll knockdown/knockout in adipose tissue and adipocytes

Common human diseases like diabetes, obesity and metabolic syndrome pose still unmet requirements for early diagnosis, treatment and care. Knowledge on mechanisms of disease is a prerequisite for safe and efficient treatment of disorders and development of medicines.
The aim of this project here is to investigate certain processes of adipogenesis on the molecular level in cell culture and a mouse model. Especially, the role of monoacylglycerol lipase (MGLL) will be characterized. The MGLL function will be modified by genetic approaches (e.g. knock down by siRNA or CRISPR/Cas technologies) or the treatment with inhibitors in the mouse and human cell models (3T3-L1 and SGBS). In parallel, an adipose tissue-specific Mgll knockout mouse at high fat diet (HFD) will be analyzed. In all models the influence of the Mgll knockout will be monitored by metabolomic and transcriptomic analyses. Data will be evaluated with integrative bioinformatics approaches (e.g. random forest or self-organizing maps) to reveal key players of the homeostasis in health and disease.  

Project Lead: Patrick Pann