Frauke Zipp, Professor of Neurology and Neuroimmunology, Rhine-Main-Neuroscience Network, Director of the Department of Neurology at the University Medical Center of the Johannes Gutenberg University Mainz, Germany, is a Clinician Scientist. As such she performs research on effector mechanisms including their biomarker and concepts of repair in inflammatory pathology of the brain such as in multiple sclerosis, with a focus on the delicate balance of the immune and nervous system in health and disease. Apart from participating on several advisory or executive boards (such as MSIF, ECTRIMS, ISNI, KKNMS) and reviewing for international journals, research agencies as well as research and clinical societies, she has published in journals such as Lancet, Cell, Nature Medicine, Nature Neuroscience, Immunity and Nature Cell Biology. Frauke Zipp has served and is active as Associate Editor and Advisor for renowned journals, has organized international meetings and is member of the National Academy of Sciences Leopoldina and the European Academia Europaea.
She is the founding speaker of two trans-regional collaborative research centers and, together with four colleagues, founding member of a German Research Foundation (DFG) excellence cluster (NeuroCure, Charité Berlin). In addition, Frauke Zipp is member of the German National Academy of Sciences Leopoldina and the European Academia Europaea. Her work focuses on inflammatory neuronal damage and repair in multiple sclerosis, with an emphasis on biomarker and therapy including activities in trial steering committees and safety boards, as well as experimental and clinical work on more general questions of the crosstalk between the nervous and immune systems. Translational work has always been her motivation and allows for successful research as well as patients´ treatment. This guiding principal does not only influence her own work given in selected papers below, but also the work of all professors recruited to the Neurology Department over the past few years. Her understanding of a University Medical Hospital combining research, teaching and clinical care is best characterized as an Academic Health Center.
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Hanuscheck, N., Thalman, C., Domingues, M., Schmaul, S., Muthuraman, M., Hetsch, F., Ecker, M., Endle, H., Oshaghi, M., Martino, G., Kuhlmann, T., Bozek, K., van Beers, T., Bittner, S., von Engelhardt, J., Vogt, J., Vogelaar, C., Zipp, F. Interleukin-4 receptor signaling modulates neuronal network activity. J Exp Med; 219(6): e20211887
Bitar, L.*, Uphaus T.*, Thalman, C.*, Muthuraman, M., Gyr, L., Ji, H., Domingues M., Endle, H., Groppa, S., Steffen, F., Koirala, N., Fan, W., Ibanez, L., Heitsch, L., Cruchaga, C., Lee, J., Kloss, F., Bittner S., Nitsch§, R., Zipp§, F., Vogt§, J. Inhibition of the enzyme autotaxin reduces cortical excitability and ameliorates the outcome in stroke. Science Translational Medicine, Vol 14, Issue 641
*equally contributing first authors, §equally contributing senior authors
Engel, S., Zipp, F. Preventing disease progression in multiple sclerosis—insights from large real-world cohorts. Genome Med 14, 41.
Bittner S & Zipp F. A lymphocyte-glia connection sets the pace for smoldering Inflammation. Cell; 184(23): 5696-5698.
Bittner S, Oh J, Havrdova EK, Tintore M, Zipp F. The potential of serum neurofilament as biomarker for multiple sclerosis. Brain; 144(19): 2954-2963.
Wasser B*, Luchtman D*, Löffel J, Robohm K, Birkner K, Stroh A, Vogelaar CF, Zipp F§, Bittner S§. CNS-localized myeloid cells capture living invading T cells during neuroinflammation. J Exp Med; 217(6): e20190812. *equally contributing, §equally contributing and corresponding
Birkner K, Wasser B, Ruck T, Thalman C, Luchtman D, Pape K, Schmaul S, Bitar L, Krämer-Albers EM, Stroh A, Meuth S, Zipp F§, Bittner S§. ß1-Integrin- and KV1.2 Channel-Dependent Signaling Stimulates Glutamate Release From Th17 Cells. J Clin Invest 130(2): 715-732. § equally contributing and corresponding
International Multiple Sclerosis Genetics Consortium*. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science; 365: eaav7188. *FZ in governance group
Pape K, Tamouza R, Leboyer M, Zipp F. Immunoneuropsychiatry - novel perspectives on brain disorders. Nat Rev Neurol; 15: 317-328.
Ellwardt E*, Pramanik G*, Luchtman D, Novkovic T, Rosales Jubal E, Vogt J, Arnoux I, Vogelaar CF, Mandal S, Schmalz M, Barger Z, Ruiz de Azua I, Kuhlmann T, Lutz B, Mittmann T, Bittner S, Zipp F§, Stroh A§. 2018. Maladaptive cortical hyperactivity upon recovery from experimental autoimmune encephalomyelitis. Nat Neurosci 21(10): 1392-1403. *equally contributing, §equally contributing and corresponding
Bittner S, Zipp F. AAN unveils new guidelines for MS disease-modifying therapy. Nat Rev Neurol; 14(7): 384-386.
International Multiple Sclerosis Genetics Consortium*. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk. Cell; 175: 1–9. *FZ in governance
Vogelaar CF*, Mandal S*, Lerch S*, Birkner K, Birkenstock J, Bühler U, Schnatz A, Raine CS, Bittner S, Vogt J, Kipnis J, Nitsch R, Zipp F. 2018. Fast direct neuronal signaling via the IL-4 receptor as therapeutic target in neuroinflammation. Sci Transl Med 10(430): eaao2304. * equally contributing
Larochelle C*, Uphaus T*, Broux B, Gowing E, Paterka M, Michel L, Dudvarski Stankovic N, Bicker F, Lemaitre F, Prat A§, Schmidt MMH§, Zipp F§. 2018. EGFL7 reduces CNS inflammation in mouse. Nat Commun 9(1): 819. *,§ equally contributing
Paterka M, Siffrin V, Voss JO, Werr J, Hoppmann N, Gollan R, Belikan P, Bruttger J, Birkenstock J, Esplugues E, Yogev N, Flavell RA, Bopp T, Zipp F. 2016. Gatekeeper role of antigen-presenting CD11c+ cells in neuroinflammation. EMBO Journal 35(1): 89-101.
Ulges A, Witsch E, Pramanik G, Klein M, Birkner K, Bühler U, Wasser, B, Luessi, F, Stergiou N, Dietzen S, Brühl T-J, Bohn T, Bündgen G, Kunz H, Waisman A, Schild H, Schmitt E, Zipp F§, Bopp T§. 2016. Protein kinase CK2 governs the molecular decision between encephalitogenic TH17 cell and Treg cell development. Proc Natl Acad Sci USA 113(36): 10145-50. § equally contributing
Larochelle C, Uphaus T, Prat A, Zipp F. 2016. Secondary progression in multiple sclerosis: neuronal exhaustion or distinct pathology? Trends Neurosci 39(5): 325-339
Ellwardt E, Walsh JT, Kipnis J, Zipp F. 2016. Understanding the Role of T Cells in CNS Homeostasis. Trends Immunol 37(2): 154-65.
Walsh, J. T., Hendrix, S., Boato, F., Smirnov, I., Zheng, J., Lukens, J. R., Gadani, S., Hechler, D., Golz, G., Rosenberger, K., Kammertons, T., Vogt, J., Vogelaar, C., Siffrin, V., Radjavi, A., Fernandez-Castaneda, A., Gaultier, A., Gold, R., Kanneganti, T. D., Nitsch, R., Zipp §, F., and Kipnis §, J. 2015. MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4. J Clin Invest 125: 699-714. § equally contributing.
Methner, A., and Zipp, F. 2013. Multiple sclerosis in 2012: Novel therapeutic options and drug targets in MS. Nat Rev Neurol 9: 72-73.
Liblau, R. S., Gonzalez-Dunia, D., Wiendl, H., and Zipp, F. 2013. Neurons as targets for T cells in the nervous system. Trends Neurosci 36: 315-324.
IMSGC (Zipp F as part of strategy group). 2013. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet 45: 1353-1360.
Roep, B. O., Buckner, J., Sawcer, S., Toes, R., and Zipp, F. 2012. The problems and promises of research into human immunology and autoimmune disease. Nat Med 18: 48-53.
IMSGC (Zipp F as part of strategy group). 2011. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476: 214-219.
Siffrin, V., Vogt, J., Radbruch, H., Nitsch, R., and Zipp, F. 2010. Multiple sclerosis - candidate mechanisms underlying CNS atrophy. Trends Neurosci 33: 202-210.
Siffrin, V., Radbruch, H., Glumm, R., Niesner, R., Paterka, M., Herz, J., Leuenberger, T., Lehmann, S. M., Luenstedt, S., Rinnenthal, J. L., Laube, G., Luche, H., Lehnardt, S., Fehling, H. J., Griesbeck, O., and Zipp, F. 2010. In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis. Immunity 33: 424-436.
Schulze-Topphoff, U., Prat, A., Prozorovski, T., Siffrin, V., Paterka, M., Herz, J., Bendix, I., Ifergan, I., Schadock, I., Mori, M. A., Van Horssen, J., Schroter, F., Smorodchenko, A., Han, M. H., Bader, M., Steinman, L., Aktas, O., and Zipp, F. 2009. Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system. Nat Med 15: 788-793.
Prozorovski, T., Schulze-Topphoff, U., Glumm, R., Baumgart, J., Schroter, F., Ninnemann, O., Siegert, E., Bendix, I., Brustle, O., Nitsch, R., Zipp §, F., and Aktas §, O. 2008. Sirt1 contributes critically to the redox-dependent fate of neural progenitors. Nat Cell Biol 10: 385-394. § equally contributing.
Hoffmann, O., Priller, J., Prozorovski, T., Schulze-Topphoff, U., Baeva, N., Lunemann, J. D., Aktas, O., Mahrhofer, C., Stricker, S., Zipp §, F., and Weber §, J. R. 2007. TRAIL limits excessive host immune responses in bacterial meningitis. J Clin Invest 117: 2004-2013. § equally contributing.
Zipp, F., and Aktas, O. 2006. The brain as a target of inflammation: common pathways link inflammatory and neurodegenerative diseases. Trends Neurosci 29: 518-527.
Aktas, O., Smorodchenko, A., Brocke, S., Infante-Duarte, C., Schulze Topphoff, U., Vogt, J., Prozorovski, T., Meier, S., Osmanova, V., Pohl, E., Bechmann, I., Nitsch, R., and Zipp, F. 2005. Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL. Neuron 46: 421-432.
Wandinger, K. P., Lunemann, J. D., Wengert, O., Bellmann-Strobl, J., Aktas, O., Weber, A., Grundstrom, E., Ehrlich, S., Wernecke, K. D., Volk, H. D., and Zipp, F. 2003. TNF-related apoptosis inducing ligand (TRAIL) as a potential response marker for interferon-beta treatment in multiple sclerosis. Lancet 361: 2036-2043
Diestel, A., Aktas, O., Hackel, D., Hake, I., Meier, S., Raine, C. S., Nitsch §, R., Zipp §, F., and Ullrich §, O. 2003. Activation of microglial poly(ADP-ribose)-polymerase-1 by cholesterol breakdown products during neuroinflammation: a link between demyelination and neuronal damage. J Exp Med 198: 1729-1740. § equally contributing.
Aktas, O., Waiczies, S., Smorodchenko, A., Dorr, J., Seeger, B., Prozorovski, T., Sallach, S., Endres, M., Brocke, S., Nitsch, R., and Zipp, F. 2003. Treatment of relapsing paralysis in experimental encephalomyelitis by targeting Th1 cells through atorvastatin. J Exp Med 197: 725-733.
Nitsch, R., Bechmann, I., Deisz, R. A., Haas, D., Lehmann, T. N., Wendling, U., and Zipp, F. 2000. Human brain-cell death induced by tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL). Lancet 356: 827-828.
Zipp, F., Weil, J. G., and Einhaupl, K. M. 1999. No increase in demyelinating diseases after hepatitis B vaccination. Nat Med 5: 964-965.