Dr. Henning Großkopf

 Postdoc in the group of Functional Genomics

Investigation of glycosaminoglycans-protein interactions

Due to the demographic change, a considerable increase of bone defects and chronic wounds can be observed. The Transregio 67 research program of the German Research Foundation (DFG) aims for the development of novel biomaterials that support the healing capacities in skin and bone defects. As components of the physiological extracellular matrix, glycosaminoglycans (GAG) are in the focus of this research.
In this project, cellular adaptions to GAG-treatment in terms of altered protein expression or activity of specific signaling pathways are investigated utilizing mass spectrometry-based, quantitative proteomics, and phosphoproteomics. A special focus is on the identification of novel GAG-interacting proteins by means of affinity-purification MS (AP-MS).

The impact of pollutants on ubiquitin-mediated signaling processes of the aryl hydrocarbon receptor in macrophages

The aryl hydrocarbon receptor (AhR) is activated by endogenous ligands, as well as, pollutants, e.g. dioxins and polycyclic aromatic hydrocarbons from combustion processes. The formed receptor-ligand complex translocates to the nucleus and stimulates the expression of target genes. Among these are enzymes which are involved in the metabolisation of xenobiotics, including proteins of the cytochrome P450-family. In addition, the AhR acts as a substrate recognition subunit of Cullin-RING ubiquitin ligases. The complex ubiquitinates target proteins specifically and thus initiates their degradation.
In the course of immunoreactions, the AhR has a regulatory role. Thereby it provides either pro- or anti-inflammatory signals, depending on the specific ligand and cell type. On the one hand, AhR interaction partners in macrophages are investigated by means of affinity-purification MS (AP-MS), in this project. On the other hand, AhR-dependent, ubiquitin-mediated signaling processes are investigated utilizing global ubiquitome and proteome approaches.

Großkopf, H.; Walter, K.; Karkossa, I.; von Bergen, M.; Schubert, K. (2021)
Non-Genomic AhR-Signaling Modulates the Immune Response in Endotoxin-Activated Macrophages After Activation by the Environmental Stressor BaP.
Frontiers in Immunology.
doi: 10.3389/fimmu.2021.620270

Wang, Z.; Karkossa, I.; Großkopf, H.; Rolle-Kampczyk, U.; Hackermüller, J.; von Bergen, M.; Schubert, K. (2020)
Comparison of quantitation methods in proteomics to define relevant toxicological information on AhR activation of HepG2 cells by BaP.
Toxicology.
doi: 10.1016/j.tox.2020.152652

Tsikas, D.; Böhmer, A.; Großkopf, H.; Beckmann, B.; Dreißigacker, U.; Jordan, J.; Massen, N. (2012)
Clinical-chemistry laboratory relevant hemolysis is unlikely to compromise human plasma concentration of free asymmetric dimethylarginine (ADMA).
Clinical Biochemistry.
doi: 10.1016/j.clinbiochem.2012.03.020

Großkopf, H.; Böhmer, A.; Tsikas, D. (2012)
Letter to the editor: “Role of the human erythrocyte in generation and storage of asymmetric dimethylarginine.”
American journal of physiology. Heart and circulatory physiology.
doi: 10.1152/ajpheart.00449.2012

Böhmer, A.; Großkopf, H.; Jordan, J.; Tsikas, D. (2012)
Human hemoglobin does not contain asymmetric dimethylarginine (ADMA).
Nitric Oxide.
doi: 10.1016/j.niox.2012.03.013