Division of Molecular Metabolic Control
Prof. Dr. Stephan Herzig
The department “Molecular Metabolic Control” is a common research unit between the German Cancer Research Center (DKFZ), the Center for Molecular Biology (ZMBH) at the University of Heidelberg and the University Hospital Heidelberg.
The department is investigating the molecular basis of severe metabolic disorders, including the Metabolic Syndrome and type 2 diabetes, and their roles in tumor initiation and progression.
The main causes of these metabolic disorders are believed to be malfunctions in the activity of genes regulating our metabolism. By analyzing the signal-dependent activity of such genes in response to hormonal, nutritional and inflammatory cues, we aim to define disease-causing malfunctions in glucose, fat and protein metabolism, ultimately aiming at the identification of genes and gene products which increase the susceptibility to metabolic diseases.
Subsequently, identified gene defects are tested for their potential to serve as molecular connections between metabolic and tumor diseases and as potential novel drug targets within these disease entities. Thus far, we have already characterized a number of molecular switches that are dysregulated under certain metabolic conditions and promote aberrant metabolism in diabetes and cancer.
In the future, we will address the question if and how the differential recruitment of specific transcriptional complexes to genomic target sites provides a molecular relay station for nutritional, hormonal and inflammatory signals in the control of energy homeostasis and the pathogenesis of aging-associated diseases, including diabetes and cancer.
Specifically, we will investigate whether and how relevant transcription factor complexes bridge metabolism, inflammation and tumor development through the integrated control of metabolic pathways, inflammatory responses, and cell fate decisions.
By using a translational research approach, we anticipate unravelling clinically significant molecular determinants in the pathogenesis of the Metabolic Syndrome and type 2 diabetes that are directly coupled to an increased cancer risk in these patients, thereby serving as potential new therapeutic targets in metabolic disorders.In particular, we will focus on three main areas
1. Transcriptional networks, systemic lipid distribution, and lipotoxicity
2. Molecular integration of inflammation and metabolism
3. Brown adipocyte stem cells and control of energy homeostasis
Center for Molecular Biology (ZMBH) at Heidelberg University
Heidelberg University Hospital
Kulozik, Ph., Jones, A., Mattijssen, F., Rose, A. J., Reimann, A., Strzoda, D., Kleinsorg, S., Raupp, Ch., Kleinschmidt, J., Müller-Decker, K., Wahli, W., Sticht, C., Gretz, N., von Loeffelholz, Ch., Stockmann, M., Pfeiffer, A., Stöhr, S., Dallinga-Thie, G. M., Nawroth, P. P., Berriel Diaz M. and Herzig, S. (2011). Hepatic deficiency in transcriptional co-factor TBL1 promotes liver steatosis and hypertriglyceridemia. Cell Metabolism, 13, 389–400
Vegiopoulos, A., Müller-Decker, K., Strzoda, D., Schmitt, I., Chichelnitskiy, E., Ostertag, A., Berriel Diaz, M., Rozman, J., Hrabe de Angelis, M., Nüsing, R.M., Meyer, C., Wahli, W., Klingenspor, M., and Herzig, S. (2010). COX-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science, 328, 1158-1161
Lemke, U., Krones-Herzig, A., Berriel Diaz, M., Narvekar, P., Ziegler, A., Vegiopoulos, A., Bohl, S., Klingmüller, U., Cato, A., Screaton, R., Müller-Decker, K., Kersten, S., and Herzig, S. (2008). The glucocorticoid receptor controls hepatic dyslipidemia through Hes1. Cell Metab., 8, 212-223
Herzig, S., Long, F., Jhala, U.S., Hedrick, S., Quinn, R., Bauer, A., Rudolph, D., Schütz, G., Yoon, C., Puigserver, P., Spiegelman, B., and Montminy, M. (2001). CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature, 413, 179-183