Charité - Universitätsmedizin Berlin
Campus Benjamin Franklin
Phone: +49 30 450 514343
In the tumor microenvironment, the metabolic milieu differs tremendously from healthy tissue. Glycolysis and fatty acid oxidation are out of balance; you find ongoing hypoxia, inflammation and regeneration. In our previous and recent studies, we see a clear effect of unsaturated fatty acids like oleic acid on the functional polarization of myeloid cells into a monocytic MDSC - as well as a TAM-like phenotype. We could also link this phenotype directly to the formation of lipid droplets inside these cells and an increased fatty acid oxidation compared to control groups. To discover the metabolic pathways and switches to modulate myeloid cell phenotypes in the context of tumor but also intestinal inflammation is one of our major projects in the group. Therefore, we will analyze different tumor entities for their fatty acid content as well as the role of lipid droplet bearing macrophages within these tumors. Ultimately, we will develop interventional strategies to reduce the regulatory effect of tumor-associated macrophages using specific carriers to deliver metabolic inhibitors.
We will decipher the intracellular pathway of external ingested free fatty acids of macrophages and will describe the functional role of lipid droplets as critical organelles using the respective KO mice.
- Rainer Glauben - PI
- Inka Freise - Technician
- Hsiang-Jung Hsiao - PhD student
- Yasmina Rodriguez Silke - PhD student
- Lorenz Gerbeth - PhD student
- Sophiya Siddiqui - PhD student
- Wu, H., Y. Han, Y. Rodriguez Silke, H. Deng, S. Siddiqui, C. Treese, F. Schmidt, M. Friedrich, J. Keye, J. Wan, Y. Qin, A. A. Kuhl, Z. Qin, B. Siegmund, and R. Glauben. 2019. Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages. EMBO Mol Med 11: e10698
- 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.