Hormonal regulation and novel mechanism for the resolution of inflammation

Research directions:

  • Hormonal control and regulation of inflammatory processes
  • Regulators during inflammation and the resolution of inflammation

 

Inflammation is a natural reaction of the body to invading pathogens. Depending on the type of inflammatory response and pathology, it can occur as acute (sepsis, lung inflammation) or chronic inflammation. In addition, during inflammation, cells are exposed to constant mechanical stresses that influence their inflammatory status. The reduction of inflammation that in turn later supports the resolution inflammation is a crucial mechanism to revert the body back to a healthy status.

My group aims to investigate novel hormonal driven mechanisms in inflammation. With the aim to identify and target new regulators for anti-inflammatory processes, and pro-resolving mechanisms to accelerate the resolution of inflammatory processes.

[Translate to english:] AG Vettorazzi

 

 

Projects

1. Reversibility of long-term glucocorticoid effects

In this DFG funded project, we look at the long-term effects of glucocorticoid therapy in murine tissues. Glucocorticoids are widely prescribed to treat inflammatory diseases. The aim of this project is to understand glucocorticoid effects in non-immune cells to evaluate mechanisms involved in the adverse effects of glucocorticoid therapy. This project is a cooperation with Dr. Franziska Greulich at the TUM School of Life Science. We are using mouse models, histology, molecular biology, next-generation sequencing and single-cell analysis. We are looking for master students as well as student aids (HIWI) soon. If you are interested in this project, please contact me directly (sabine.vettorazzi(at)uni-ulm.de).

2. Peripheral nerve injury: cross-talk between Schwann cells and macrophages

Peripheral nerve injury affects 5% of all admitted trauma patients. Regeneration potential and functional recovery of peripheral nerves varies depending on age, injury severity and location. Schwann cells are the main drivers of peripheral nerve regeneration after injury by switching from a differentiated to a regenerative repair state. In addition, efficient macrophage phagocytosis is important to clear tissue debris from injury site and a crucial step in the degeneration phase to ensure a successful following regeneration phase. In this DFG funded project, within the CRC 1149 (danger response, disturbance factors and regenerative potential after acute trauma) we investigate the cross-talk between Schwann cells and macrophages and will identify crucial factors to enhance the regeneration potential after peripheral nerve injury. We are looking for PhD students as well as master. If you are interested in this project, please contact me directly.

3. Combined effects of adrenal gland hormones

Adrenal gland hormones contribute to an important extent during inflammatory processes by fostering the resolution of inflammation by their action on immune cells. This project aims to understand the underlying mechanisms in various inflammation models as well as the translational aspect into humans. We are looking for master and bachelor students. If you are interested in this project, please contact me directly (sabine.vettorazzi(at)uni-ulm.de).

4. Mechanostimulation

During inflammation (immune) cells are constantly experience to mechanical stimulation. In this project we investigate the impact of mechanostimulation and the role of nuclear receptors during (resolution of) inflammation. We are looking for master and bachelor students. If you are interested in this project, please contact me directly (sabine.vettorazzi(at)uni-ulm.de).

5. Arthritis (in cooperation with Prof. Dr. Tuckermann)

Glucocorticoids are used to treat rheumatoid arthritis in patients due to their potent anti-inflammatory actions, however their long-term use is compromised by side effects (glucocorticoid resistance and insulin, osteoporosis). In this project we aim to investigate the role of anti-inflammatory glucocorticoids in immune and non-immune cells during arthritis. We are looking for master and bachelor students. If you are interested in this project, please contact me directly (sabine.vettorazzi(at)uni-ulm.de).

 

Selected publications

Wepler, M., Preuss, J.M., Tilp, C., Keck, M., Blender, J., Wachter, U., Merz, T., Vogt, J.,Kress, S.,Groeger, M., Hoffmann, A., Fink, M., Calzia, E., Burret, U., Radermacher, P.,Tuckermann, J.,  Vettorazzi, S. (2022) Cigarette smoke exposure reduces hemorrhagic shock induced circulatory dysfunction in mice with attenuated glucocorticoid receptor function. Front. Immunol., 13;980707

Preuss JM., Burret U., Gröger M., Kress S., Scheuerle A., Möller P., Tuckermann JP., Wepler M., Vettorazzi S. (2021), Impaired glucocorticoid receptor signaling aggravates lung injury after hemorrhagic shock, Cells, doi: 10.3390/cells11010112

Stifel, U., Wolfschmitt, E.-M., Vogt, J., Wachter, U., Vettorazzi, S., Tews, D., Hogg, M., Zink, F., Koll, N. M., Winning, S., Mounier, R., Chazaud, B., Radermacher, P., Fischer-Posovszky, P., Caratti, G., and Tuckermann, J. (2021) Glucocorticoids Coordinate Macrophage Metabolism Through Regulation of the Tricarboxylic Acid Cycle. Mol. Metab., doi: 10.1016/j.molmet.2021.101424.

Vettorazzi, S., Nalbantoglu, D., Christof, J., Gebhardt, M., Tuckermann, J., Gebhardt, J. C. M., and Tuckermann, J. (2021) A guide to changing paradigms of glucocorticoid receptor function—a model system for genome regulation and physiology. FEBS J., doi: 10.1111/febs.16100.

Pfänder, P., Eiers, A.-K., Burret, U., Vettorazzi, S. (2021) Deletion of Cdk5 in Macrophages Ameliorates Anti-Inflammatory Response during Endotoxemia through Induction of C-Maf and Il- 10. Int. J. Mol. Sci. Artic., doi: 10.3390/ijms22179648.

S. Vettorazzi, C. Bode, L. Dejager, L. Frappart, E. Shelest, C. Klassen, A. Tasdogan, H.M. Reichardt, C. Libert, M. Schneider, F. Weih, N.H. Uhlenhaut, J.-P. David, M. Graeler, A. Kleiman, J.P. Tuckermann (2015), Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1, Nature Communications, doi: 10.1038/ncomms8796.

Further publications by Dr. Sabine Vettorazzi can be found in our publications directory.

 

Current lab members

08/2019 - 01/2024, PhD student Jonathan Preuß, University Ulm „ Crosstalk of adrenal gland hormones“

01/2020 - current, PhD student Denis Nalbantoglu, University Ulm „ Mechanostimulation in the innate immune system”

07/2022 - current, PhD Student Ann-Kathrin Eiers, University Ulm „Regulation of fibroblast-like synoviocytes by glucocorticoids in arthritis"

02/2023 - current, PhD Gizem Öztürk, Doktorand Universität Ulm, „Reversibility of long-term glucocorticoid effects"

04/2023 – current PhD, Lorena-Madeleine Witzl, University Ulm

“Glucocorticoids influence Schwann cell and macrophage responses in a mouse      

  model of peripheral nerve injury”

07/2023 – current, Masterstudent, Matthias Bauer, University Ulm

Biological Technical Assistant, Ute Burret

Alumni

Bachelor students

  • 11/2013 Ferdinand Schlichtig, Bachelor, University Ulm „Regulation of gene expression in primary macrophages under inflammatory conditions “
  • 10/2014 Aline Gold-Jaudas, Bachelor, University Ulm „Regulation entzündlicher Mediatoren in Makrophagen durch den Glucocorticoidrezeptor“
  • 04/2016 Pauline Pfänder, Bachelor, University Ulm „Die Wirkung von CDK5-Inhibitor Roscovitin und Dexamethason in LPS-stimulierten Makrophagen“
  • 06/2016 Sonja Schmuker, Bachelor, University Ulm „The impact of Axl in macrophages“
  • 03/2019 Kalvin Nugraha, Bachelor, University Ulm „The impact of Sphk1 deletion in myeloid cells on the expression of adipogenic genes and macrophages in mice eWAT”
  • 07/2019 Lena Lipinski, Bachelor, University Ulm „Role of Cdk5 in the anti-inflammatory process of glucocorticoids”
  • 03/2021 Sandra Hägele, Bachelor, College Reutlingen „Exploring the synergism of β-adrenergic agonist and glucocorticoids in endothelial cells and macrophages“
  • 03/2021 Franziska Meichsner, Bachelor, University Ulm „Regulation of Yap signaling by glucocorticoids“
  • 09/2021 Luana Bajer, Bachelor, College Esslingen „Etablierung eines mit Zigarettenrauch behandelten Zellkultursystems zur Untersuchung von COPD molekularen Mechanismen“
  •  10/2021 Katharina Oßwald, Bachelor, University Ulm „(Reversible) long term glucocorticoid effects on metabolism and bone”
  • 08/2022 - current, Sebastian Lehner, Bachelorstudent, University Ulm „Long term Glucocorticoid effects on bone mediated via the Glucocorticoid receptor"

Masterarbeiten

  • 08/2015 Rebecca Zeh, Master, University Ulm „The role of SphK1 in Immunometabolism”
  • 05/2016 Carmen Jessica Strobel, Master, College Albstadt-Sigmaringen „Establishment and modification of primary macrophages and characterization after treatment”
  • 11/2016 Miray Fidan, Master, University Ulm „Polarization of primary macrophages and the impact of glucocorticoids”
  • 04/2017 Hannah Luisa Peters, Master Psychologie, University Trier „Die Rolle der Glucocorticodrezeptor Dimerisation bei einer systemischen  Entzündungs-reaktion: ein pathogenetischer Mechanismus der entzündungsbedingten Depression?”
  • 05/2017 Pauline Pfänder, Master, University Ulm „The role of CDK5 in macrophages”
  • 07/2019 Jonathan Preuß, Master, University Ulm „Impairment of GR dimerization affects lung compliance and immune status”
  • 06/2022 - current, Ann-Kathrin Eiers, Master, University Ulm „The impact of attenuated glucocorticoid receptor dimerization in stromal cells in rheumatoid arthritis & The role of Cdk5 deletion in myeloid cells during acute inflammation"

Group leader