Dr. rer. nat. Rainer Glauben

AG Siegmund
Division of Gastroenterology, Infectiology, and Rheumatology
Charité - Universitätsmedizin Berlin
Tel: +49 30 450 514343

E-Mail: rainer.glauben(at)charite.de
https://gastro.charite.de/forschung/ag_siegmund/

Scientific Scope

Class II histone deacetylases (HDAC) orchestrate T cell-dependent immune responses via epigenetic control of genes and via post-translational modifications. When T cell-specific HDAC7-KO mice were analyzed by mass cytometry, they revealed a highly pre-activated phenotype of CD8+ T cells. Further analysis via infection and tumor models demonstrated an impaired cytokine production, memory recall response and cytotoxic killing capacity. This phenotype could be linked to reduced SOCE and transcriptional deregulation of metabolism- and apoptosis-regulating genes resulting in an impaired glycolytic capacity and apoptosis of CD8+ T cells. These results could be confirmed in virus infection models as well as in tumor transplantation models. To identify the mechanisms how HDAC7 and other HDACs modulate the phenotype of adult T cells, especially how they control the tumor killing capacity, is one of our long standing goals in the group.

Selected References

  • Friedrich, M., Gerbeth L., Gerling M., Rosenthal R., Steiger K., Weidinger C., Keye J., Wu H., Schmidt F., Weichert W., Siegmund B., and Glauben R. HDAC inhibitors promote intestinal epithelial regeneration via autocrine TGFbeta1 signalling in inflammation. Mucosal immunology. 2019;12(3):656-67.
  • Bottcher, C., Schlickeiser S., Sneeboer M. A. M., Kunkel D., Knop A., Paza E., Fidzinski P., Kraus L., Snijders G. J. L., Kahn R. S., Schulz A. R., Mei H. E., Psy N. B. B., Hol E. M., Siegmund B., Glauben R., Spruth E. J., de Witte L. D., and Priller J. Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry. Nature neuroscience. 2019;22(1):78-90.
  • Wu, H., Weidinger C., Schmidt F., Keye J., Friedrich M., Yerinde C., Willimsky G., Qin Z., Siegmund B., and Glauben R. Oleate but not stearate induces the regulatory phenotype of myeloid suppressor cells. Scientific reports. 2017;7(1):7498.
  • Poralla, L., Stroh T., Erben U., Sittig M., Liebig S., Siegmund B., and Glauben R. Histone deacetylase 5 regulates the inflammatory response of macrophages. Journal of cellular and molecular medicine. 2015;19(9):2162-71.
  • Glauben, R., Sonnenberg E., Wetzel M., Mascagni P., and Siegmund B. Histone deacetylase inhibitors modulate interleukin 6-dependent CD4+ T cell polarization in vitro and in vivo. The Journal of biological chemistry. 2014;289(9):6142-51.