A13

A13

In stroke, brain damage and secondary infarct growth are determined by local inflammatory reactions and blood-brain barrier breakdown which, in turn, are influenced by enzymes responsible for the conversion of ATP into adenosine (ADO), such as CD39 and CD73. The expression of CD73 differs substantially between human and murine cerebral endothelial cells and microglia. We will use targeted AAV vectors and nanobodies to humanize the ATP degradation pathways in murine cerebral EC and microglia in vivo, which will enable the assessment of the functional relevance of ATP breakdown/ purinergic signaling in the brain.

Prof. Dr. Tim Magnus

Selected publications (*equal contribution)

 

1. Winzer, R., Serracant-Prat, A., Brock, V. J., Pinto-Espinoza, C., Rissiek, B., Amadi, M., Eich, N., Rissiek, A., Schneider, E., Magnus, T., Guse, A. H., Diercks, B. P., Koch-Nolte, F. & Tolosa, E. (2022) P2X7 is expressed on human innate-like T lymphocytes and mediates susceptibility to ATP-induced cell death, Eur J Immunol.
2. Wilmes, M., Pinto Espinoza, C., Ludewig, P., Stabernack, J., Liesz, A., Nicke, A., Gelderblom, M., Gerloff, C., Falzoni, S., Tolosa, E., Di Virgilio, F., Rissiek, B., Plesnilla, N., Koch-Nolte, F. & Magnus, T. (2022) Blocking P2X7 by intracerebroventricular injection of P2X7-specific nanobodies reduces stroke lesions, J Neuroinflammation. 19, 256.
3. Schadlich, I. S., Schnapauff, O., Pols, L., Schrader, J., Tolosa, E., Rissiek, B. & Magnus, T. (2022) Nt5e deficiency does not affect post-stroke inflammation and lesion size in a murine ischemia/reperfusion stroke model, iScience. 25, 104470.
4. Schneider, E., Winzer, R., Rissiek, A., Ricklefs, I., Meyer-Schwesinger, C., Ricklefs, F. L., Bauche, A., Behrends, J., Reimer, R., Brenna, S., Wasielewski, H., Lauten, M., Rissiek, B., Puig, B., Cortesi, F., Magnus, T., Fliegert, R., Muller, C. E., Gagliani, N. & Tolosa, E. (2021) CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression, Nat Commun. 12, 5911.
5. Ramirez-Fernandez, A., Urbina-Trevino, L., Conte, G., Alves, M., Rissiek, B., Durner, A., Scalbert, N., Zhang, J., Magnus, T., Koch-Nolte, F., Plesnila, N., Deussing, J. M., Engel, T., Kopp, R. & Nicke, A. (2020) Deviant reporter expression and P2X4 passenger gene overexpression in the soluble EGFP BAC transgenic P2X7 reporter mouse model, Sci Rep. 10, 19876.
6. Er-Lukowiak, M., Duan, Y., Rassendren, F., Ulmann, L., Nicke, A., Ufer, F., Friese, M. A., Koch-Nolte, F., Magnus, T. & Rissiek, B. (2020) A P2rx7 Passenger Mutation Affects the Vitality and Function of T cells in Congenic Mice, iScience. 23, 101870.
7. Brenna, S., Altmeppen, H. C., Mohammadi, B., Rissiek, B., Schlink, F., Ludewig, P., Krisp, C., Schluter, H., Failla, A. V., Schneider, C., Glatzel, M., Puig, B. & Magnus, T. (2020) Characterization of brain-derived extracellular vesicles reveals changes in cellular origin after stroke and enrichment of the prion protein with a potential role in cellular uptake, J Extracell Vesicles. 9, 1809065
8. Rissiek, B., Stabernack, J., Cordes, M., Duan, Y., Behr, S., Menzel, S., Magnus, T. & Koch-Nolte, F. (2019) Astrocytes and Microglia Are Resistant to NAD(+)-Mediated Cell Death Along the ARTC2/P2X7 Axis, Front Mol Neurosci. 12, 330.
9. Rissiek, B., Lukowiak, M., Raczkowski, F., Magnus, T., Mittrucker, H. W. & Koch-Nolte, F. (2018) In Vivo Blockade of Murine ARTC2.2 During Cell Preparation Preserves the Vitality and Function of Liver Tissue-Resident Memory T Cells, Front Immunol. 9, 1580.
10. Kaczmarek-Hajek, K., Zhang, J., Kopp, R., Grosche, A., Rissiek, B., Saul, A., Bruzzone, S., Engel, T., Jooss, T., Krautloher, A., Schuster, S., Magnus, T., Stadelmann, C., Sirko, S., Koch-Nolte, F., Eulenburg, V. & Nicke, A. (2018) Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody, Elife. 7.

PD Dr. Jakob Körbelin

Selected publications (*equal contribution)

 

1. Stamataki M, Lüschow J, Schlumbohm C, Alawi M, Lunding L, Fuchs E, Trepel M*, Schwaninger M*, Körbelin J*. Identification of AAV variants with improved transduction of human vascular endothelial cells by screening AAV capsid libraries in non-human primates. Gene Ther 2025 Oct;32(5):529-541. 
2. Vandal M, Institoris A, Reveret L, Korin B, Gunn C, Hirai S, Jiang Y, Lee S, Lee J, Bourassa P, Mishra RC, Peringod G, Arellano F, Belzil C, Tremblay C, Hashem M, Gorzo K, Elias E, Yao J, Meilandt B, Foreman O, Roose-Girma M, Shin S, Muruve D, Nicola W, Körbelin J, Dunn JF, Chen W, Park SK, Braun AP, Bennett DA, Gordon GRJ, Calon F, Shaw AS, Nguyen MD. Loss of endothelial CD2AP causes sex-dependent cerebrovascular dysfunction. Neuron 2025 Mar 19;113(6):876-895.e11.
3. Toma K, Zhao M, Zhang S, Wang F, Graham HK, Zou J, Modgil S, Shang WH, Tsai NY, Cai Z, Liu L, Hong G, Kriegstein AR, Hu Y, Körbelin J, Zhang R, Liao YJ, Kim TN, Ye X, Duan X. Perivascular neurons instruct 3D vascular lattice formation via neurovascular contact. Cell 2024 May 23;187(11):2767-2784.e23. 
4. Wu G, Liu S, Hagenstein J, Alawi M, Hengel FE, Schaper M, Akyüz N, Liao Z, Wanner N, Tomas NM, Failla AV, Dierlamm J, Körbelin J*, Lu S*, Huber TB*. Adeno-associated virus-based gene therapy treats inflammatory kidney disease in mice.  J Clin Invest 2024 Aug 15;134(17):e174722. 
5. Mehina EMF, Taylor S, Boghozian R, White E, Choi SE, Cheema MS, Körbelin J, Brown (2021) Invasion of phagocytic Galectin 3 expressing macrophages in the diabetic brain disrupts vascular repair. Sci AdvAug 18;7(34):eabg2712.
6. Ren AA, Snellings DA, Su YS, Hong CC, Castro M, Tang AT, Detter MR, Hobson N, Girard R, Romanos S, Lightle R, Moore T, Shenkar R, Benavides C, Beaman MM, Mueller-Fielitz H, Chen M, Mericko P, Yang J, Sung DC, Lawton MT, Ruppert M, Schwaninger M, Körbelin J, Potente M, Awad IA, Marchuk DA, Kahn ML (2021) PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism. Nature Jun;594(7862):271-276.
7. Yousef H, Czupalla CJ, Lee D, Chen MB, Burke AN, Zera KA, Zandstra J, Berber E, Lehallier B, Mathur V, Nair RV, Bonanno LN, Yang AC, Peterson T, Hadeiba H, Merkel T, Körbelin J, Schwaninger M, Buckwalter MS, Quake SR, Butcher EC, Wyss-Coray T (2019) Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1. Nat Med  Jun;25(6):988-1000
8. Körbelin J, Hunger A, Alawi M, Sieber T, Binder M, Trepel M. (2017) Optimization of design and production strategies for novel adeno-associated viral display peptide libraries. Gene Ther 24(8):470-481
9. Körbelin J, Dogbevia G, Michelfelder S, Ridder D, Hunger A, Wenzel J, Seismann H, Lampe M, Bannach J, Pasparakis M, Kleinschmidt J, Schwaninger M, Trepel M. (2016) A brain microvasculature endothelial cell-specific viral vector with the potential to treat neurovascular and neurological diseases. EMBO Mol Med 1;8(6):609-25
10. Körbelin J, Sieber T, Michelfelder S, Lunding L, Spies E, Hunger A, Alawi M, Rapti K, Indenbirken D, Müller O, Pasqualini R, Arap W, Kleinschmidt J, Trepel M. (2016) Pulmonary Targeting of Adeno-associated Viral Vectors by Next-generation Sequencing-guided Screening of Random Capsid Displayed Peptide Libraries. Mol Ther; 24(6):1050-61

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