Intravital imaging study of leukocyte motility and function during CNS autoimmunity
Molecular Biology and Physiology of Neurons and Glial Cells
Final Report Abstract
During my Heisenberg fellowship, I applied my expertise, EAE intravital imaging and activation sensors. By further developing these, I showed calcium activities in encephalitogenic T cells in vivo. At each step of their in vivo migration, the encephalitogenic T cells get characteristic calcium signaling and each step can be used as therapeutic target. I also used my rat EAE model to evaluate human autoantibodies. This method directly shows the pathogenicity of human derived autoantibody and can be used for many different projects. I adopted newly developed technologies, such as CRIPSR/Cas gene editing and Next Generation Sequencing. Especially, CRISPR/Cas gene editing is a very powerful tool and will be continuously used in my research projects. In addition, I started research about autoreactive B cells in EAE. Despite their obvious importance as shown by the efficacy of B cell depletion therapies in MS, the function of B cells in the CNS is still largely unknown. I also expanded my research interest to T cell stimulation in the GALT. This is a very hot topic in all areas of neurouinflammation/neurodegeneration and I believe the research in this field will provide a lot of useful information. I believe my existing expertise together with the newly acquired one will contribute significantly. I started some collaboration during my Heisenberg fellowship, within the Institute, Biomedical Center, national and international. Some of them resulted already in publications. I would like to continue contributing to others by proving my expertise in future. Taken together, this Heisenberg fellowship enabled me to build a solid foundation for my scientific career, to deepen my understanding and to intensify my experience which in turn made me an interesting collaborator for many scientists in the field. Successful projects within these frameworks but also in my own lab that were funded by the Heisenberg fellowship ultimately resulted in a permanent position at the LMU in Munich.
Publications
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In vivo imaging in autoimmune diseases in the central nervous system.
Allergology International, Vol. 65. 2016, Issue 3, pp. 235-242.
Kawakami N.
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Post-CNS-inflammation expression of CXCL12 promotes the endogenous myelin/neuronal repair capacity following spontaneous recovery from multiple sclerosis-like disease. Journal of Neuroinflammation, Vol. 13. 2016, Article number: 7.
Zilkha-Falb R., Kaushansky N., Kawakami N., Ben-Nun A.
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A Novel Cervical Spinal Cord Window Preparation Allows for Two-Photon Imaging of T-Cell Interactions with the Cervical Spinal Cord Microvasculature during Experimental Autoimmune Encephalomyelitis. Frontiers in Immunology, Vol. 8. 2017, 406.
Haghayegh Jahromi N., Tardent H., Enzmann G., Deutsch U., Kawakami N., et al.
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Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses. Immunity, Vol. 46. 2017, Issue 1, pp. 120-132.
Druzd D., Matveeva O., Ince L., Harrison U., He W., Schmal C., Herzel H., Tsang A.H., Kawakami N., et al.
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Visualizing context-dependent calcium signaling in encephalitogenic T cells in vivo by two-photon microscopy. Proceedings of the National Academy of Sciences of the USA, Vol. 114. 2017, no. 31, E6381-E6389.
Kyratsous N.I., Bauer I.J., Zhang G., Pesic M., Bartholomäus I., Mues M., Fang P., Wörner M., Everts S., Ellwart J.W., Watt J.M., Potter B.V.L., Hohlfeld R., Wekerle H., Kawakami N.
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Intravital Imaging of T Cells Within the Spinal Cord. In: Masaru Ishii (ed.), Intravital Imaging of Dynamic Bone and Immune Systems. Methods in Molecular Biology, Vol. 1763. 2018, pp. 119-127.
Kawakami N.
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Pathogenicity of human antibodies against myelin oligodendrocyte glycoprotein. Annals of Neurology, Vol. 84. 2018, Issue 2, pp. 315-328.
Spadaro M., Winklmeier S., Beltrán E., Macrini C., Höftberger R., Schuh E., Thaler F.S., et al.
