Molecular mechanisms of insulin action / Foundations of insulin resistance
The proteome, which defines all the proteins of a tissue, a cell or a compartment, is highly dynamic and reacts directly to set stimuli. The parallel analysis of such complex protein networks provides new insights into protein regulation and interaction and provides important access to the identification of molecular targets and manipulated variables as well as potential biomarkers. For this purpose, the mass spectrometry-supported functional proteome analysis provides the appropriate platform.
The Proteome Analysis Unit investigates the molecular mechanisms of insulin action and the basics of insulin resistance. It utilizes a high-resolution mass spectrometer (Orbitrap ™ Fusion ™ Lumos ™ Tribrid ™) to quantify secondary protein modifications as well as identify novel predictive biomarkers for type 2 diabetes mellitus and sequelae.
Aims
One focus of our research is the analysis of fatty tissue and skeletal muscle secretagogues, especially identifying marker proteins involved in crosstalk between organs and in the pathogenesis of insulin resistance. The results of our systematic secretome examinations are summarized in the DiabesityProteom database and can be accessed at www.diabesityprot.org.
Protein Rainbow Workshop
Our annual Protein Rainbow Workshop offers the opportunity to learn about modern techniques of protein analysis and apply it to their own sample material.
Team
Selected Publications
- Franko A, Hartwig S, Kotzka J, Ruoß M, Nüssler AK, Königsrainer A, Häring H-U, Lehr S, Peter A 2019. Identification of the Secreted Proteins Originated from Primary Human Hepatocytes and HepG2 Cells. Nutrients. 11. https://doi.org/10.3390/nu11081795
- Petz A, Grandoch M, Gorski DJ, Abrams M, Piroth MA, Schneckmann R, Homann S, Müller J, Hartwig S, Lehr S, Yamaguchi Y, Wight TN, Gorressen S, Ding Z, Kötter S, Krüger M, Heinen A, Kelm M, Gödecke A, Flögel U, Fischer JW 2019. Cardiac Hyaluronan Synthesis Is Critically Involved in the Cardiac Macrophage Response and Promotes Healing After Ischemia Reperfusion Injury. Circ Res. 124: 1433-1447. https://doi.org/10.1161/CIRCRESAHA.118.313285
- Hartwig S, De Filippo E, Göddeke S, Knebel B, Kotzka J, Al-Hasani H, Roden M, Lehr S, Sell H 2019. Exosomal proteins constitute an essential part of the human adipose tissue secretome. BBA Proteins and Proteomics. 1867. https://doi.org/10.1016/j.bbapap.2018.11.009
- Keipert S, Kutschke M, Ost M, Schwarzmayr T, van Schothorst EM., Lamp D, Brachthäuser L, Hamp I, Mazibuko SE., Hartwig S, Lehr S, Graf E, Plettenburg O, Neff F, Tschöp MH, Jastroch M 2017. Long-Term Cold Adaptation Does Not Require FGF21 or UCP1. Cell Metab. 26: 437-446.e5. https://doi.org/10.1016/j.cmet.2017.07.016
- Markgraf D, Al-Hasani H, Lehr S 2016. Lipidomics-Reshaping the Analysis and Perception of Type 2 Diabetes. Int J Mol Sci. 17. https://doi.org/10.3390/ijms17111841
- Fröbel J, Hartwig S, Jourdain S, Fischer JC, Zilkens C, Kündgen A, Suckau D, Germing U, Czibere A, Lehr S 2015. Deep serum discoveries: SDF-1α and HSA fragments in myelodysplastic syndromes. Am J Hematol. 90: E185-E187. https://doi.org/10.1002/ajh.24070
- Hartwig S, Raschke S, Knebel B, Scheler M, Irmler M, Passlack W, Muller S, Hanisch F-G, Franz T, Li X, Dicken H-D, Eckardt K, Beckers J, de Angelis MH, Weigert C, Häring H-U, Al-Hasani H, Ouwens DM, Eckel J, Kotzka J, Lehr S 2014. Secretome profiling of primary human skeletal muscle cells. BBA Proteins and Proteomics. 1844: 1011-7. https://doi.org/10.1016/j.bbapap.2013.08.004
- Lehr S, Westermeier R 2013. 2-dimensional gel electrophoresis reloaded. Arch Physiol Biochem. 119: 93. https://doi.org/10.3109/13813455.2013.812122
- Hartwig S, Lehr S 2012. Difference Gel Electrophoresis (DIGE): Combination of highly efficient hexapeptide ligand library-based sample preparation with 2D DIGE for the analysis of the hidden human serum/plasma proteome. https://doi.org/10.1007/978-1-61779-573-2_12
- Lehr S, Hartwig S, Lamers D, Famulla S, Müller S, Hanisch F-G, Cuvelier C, Ruige J, Eckardt K, Ouwens DM, Sell H, Eckel J 2012. Identification and validation of novel adipokines released from primary human adipocytes. Mol Cell Proteomics. 11: M111.010504. https://doi.org/10.1074/mcp.M111.010504
Cooperations
- CIBIO - University of Trento, Laboratory of Biotechnology and Nanomedicine, Department of Cellular, Computational and Integrative Biology: V. D'Agostino
- Universitätsklinikum Tübingen, Institut für Klinische Chemie und Pathobiochemie: A. Peter
- Universität zu Lübeck, Interdisziplinäres Centrum für Biobanking-Lübeck: T. Gemoll
- Deutsches Institut für Ernährungsforschung, Nuthetal, Zentrale Regulation des Stoffwechsels: A. Kleinridders
- Universitätsklinikum Düsseldorf, Institut für Pharmakologie und Klinische Pharmakologie: M. Grandoch
Teaching Activities
- Master module: Insulin Resistance and Diabetes Mellitus 2020 (Lehr)
- Anleitung zu wissenschaftlichen Arbeiten/ Biochemisches Kolloquium (Lehr)