Research Projects

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1. Metabolic Function of the Enzyme Retinol Saturase

Our lab is aimed at understanding the function of the enzyme Retinol Saturase (RetSat) in the development of obesity and type 2 diabetes. The enzyme catalyzes the reduction of retinol to 13,14-dihydroretinol and possibly functions in other yet unknown reactions. RetSat is expressed at high levels in metabolically active tissues like liver and fat. Liver expression of RetSat is strongly regulated by fasting and feeding, suggesting that it is involved in hepatic glucose and fatty acid metabolism. Furthermore, RetSat expression is induced during adipocyte differentiation. Strategies that modify the activity of this enzyme could be used for the treatment of metabolic diseases. (Schupp et al. PNAS 2009)

2. Transcriptional Networks Regulating Mesenchymal Stem Cell Differentiation

We also study the mechanisms by which certain transcription factors determine the fate of mesenchymal stem cells. These cells can give rise to a variety of lineages such as adipocytes, osteoblasts, chondrocytes or myogenic precursors. We are particularly interested in the interaction of these transcriptional regulators with cofactors, which mediate their activity towards the modification of histones. We are trying to understand how these transcriptional networks commit cells to a defined lineage by the induction of determining factors such as PPARg, Runx2, MyoD, Sox proteins, and others. Reprogramming of these pathways may allow us to control disease related maladaptation in mesenchymal differentiation programs. (Schupp et al. JBC 2009)

3. Regulators of Glucose-Mediated Cell Adaptations

How can cells sense the availability of glucose and how are their metabolic adaptations mediated? In order to understand the underlying mechanisms we study one of the proteins that can sense glucose, the transcription factor Carbohydrate Response Element Binding Protein (ChREBP). This protein is highly expressed in hepatocytes and adipocytes and required for sugar tolerance. We want to understand how physiologic or inadequate activation of ChREBP by glucose or fructose metabolites is linked to the development of diseases like insulin resistance and type 2 diabetes. Knowledge about these mechanisms may allow for new therapies treating these diseases. (Witte et al. ENDOCRINOLOGY 2015)

4. Retinoid Metabolism in Metabolic Diseases

Vitamin A/Retinol is a fat-soluble vitamin and both enzymes and transport proteins determining retinoid homeostasis have been shown to be affected by type 2 diabetes. We want to understand whether an imbalanced retinoid homeostasis may actually be causative for a subset of metabolic diseases. This could help identifying novel targets for pharmacological interventions tackling these diseases. (Muenzner et al. MCB 2013, Fedders et al, HMBCI 2015)

5. Functions of the Tumor Suppressor p53 in Glucose and Fatty Acid Metabolism

p53 is an important tumor suppressor and its loss-of-function is associated with cell transformation and cancer development. We investigate the function of p53 in regard to glucose and fatty acid metabolism and its regulation by food intake, with the primary focus on liver.  We could show that food withdrawal stabilizes p53 protein in liver and that this is required for the adaptation of hepatic glucose metabolism to starvation. (Schupp et al. BMC GENOMICS 2013, Prokesch et al. FASEB J 2017)