Prof. Dr. Rainer Glaß

Primary research focus: Biomedical Neuroscience

Second research focus: Cellular & Systems Neuroscience

Third research focus: Molecular & Developmental Neuroscience

Keywords: TAMEP, microglia, macrophages, pericytes

Brief research description: The pathological impact of brain tumor-associated progenitor cells and myeloid cells; mechanisms of neoplastic angiogenesis. The abundance and pathological impact of parenchymal cell types in brain tumors (glioblastoma; GBM) is well established. However, recently we discovered a previously unacknowledged GBM parenchymal cell type, which we designated “TAMEP” (tumor associated cells with a myeloid expression profile). TAMEP share many features with myeloid cells, but have a different developmental origin. They derive from local progenitor cells, which are dormant in the healthy brain but get activated in brain tumors. We could specifically manipulate these progenitors in a transgenic mouse model and observed that progenitor ablation resulted in loss of TAMEP, profound reduction in glioblastoma (GBM) vascularization and diminished tumor size. In particular, we have found that TAMEP control the intratumoral vascular network and tightness of neoplastic vessels. Since TAMEP are required for the formation of the blood-tumor barrier (BTB), we hypothesize that preclinical strategies to target TAMEP are suited to diminish BTB formation and thereby facilitate the intratumoral accumulation of therapeutics in GBM.

Selected publications:

Marie N. M. Volmar, Jiying Cheng, Haitham Alenezi, Sven Richter, Alisha Haug, Zonera Hassan, Maria Goldberg, Yuping Li, Mengzhuo Hou, Christel Herold-Mende, Cecile L. Maire, Katrin Lamszus, Charlotte Flüh, Janka Held-Feindt, Gaetano Gargiulo, Geoffrey J. Topping, Franz Schilling, Dieter Saur, Günter Schneider, Michael Synowitz, Joel A. Schick, Roland E. Kälin, Rainer Glass. Cannabidiol converts NFB into a tumor suppressor in glioblastoma with defined antioxidative properties. Neuro-Oncology: 2021, doi: 10.1093/neuonc/noab095

Roland E. Kälin, Linzhi Cai, Yuping Li, Dongxu Zhao, Huabin Zhang, Jiying Cheng, Wenlong Zhang, Yingxi Wu, Katharina Eisenhut, Philipp Janssen, Lukas Schmitt, Wolfgang Enard, Friederike Michels, Charlotte Flüh, Mengzhuo Hou, Sabrina V. Kirchleitner, Sebastian Siller, Matthias Schiemann, Immanuel Andrä, Eloi Montanez, Claudio Giachino, Verdon Taylor, Michael Synowitz, Jörg-Christian Tonn, Louisa von Baumgarten, Christian Schulz, Ines Hellmann and Rainer Glass. TAMEP are brain tumor parenchymal cells controlling neoplastic angiogenesis and progression. Cell Systems. 2021; 12(3):248-262.e7. doi: 10.1016/j.cels.2021.01.002

Giorgia Mastrella, Mengzhuo Hou, Min Li, Veit M. Stoecklein, Nina Zdouc, Marie N.M. Volmar, Hrvoje Miletic, Sören Reinhard, Christel C. Herold-Mende, Susanne Kleber, Katharina Eisenhut, Gaetano Gargiulo, Michael Synowitz, Angelo L. Vescovi, Patrick N. Harter, Josef M. Penninger, Ernst Wagner, Michel Mittelbronn, Rolf Bjerkvig, Dolores Hambardzumyan, Ulrich Schüller, Jörg-Christian Tonn, Josefine Radke, Rainer Glass, and Roland E. Kälin. TargetingAPLN/APLNRImproves Antiangiogenic Efficiency and Blunts Proinvasive Side Effects of VEGFA/VEGFR2 Blockade in Glioblastoma. Cancer Res; 2019; 79(9): 2298-2313. doi: 10.1158/0008-5472.CAN-18-0881

Glass R, Synowitz M. CNS macrophages and peripheral myeloid cells in brain tumours. Acta Neuropathologica. 2014;128(3):347-62. doi: 10.1007/s00401-014-1274-2.

Kristin Stock; Jitender Kumar; Michael Synowitz; Stefania Petrosino; Roberta Imperatore; Ewan St. J. Smith; Peter Wend; Bettina Purfürst; Ulrike A. Nuber; Ulf Gurok; Vitali Matyash; Joo-Hee Wälzlein; Sridhar R. Chirasani; Gunnar Dittmar; Benjamin F. Cravatt, Stefan Momma, Gary R. Lewin, Alessia Ligresti; Luciano De Petrocellis; Luigia Cristino; Vincenzo Di Marzo; Helmut Kettenmann; Rainer Glass. Nature Medicine. 2012; 18(8): 1232-8. doi: 10.1038/nm.2827.