The main interest of our group is the understanding of (patho-)physiological mechanisms underlying the crosstalk between the immune and central nervous systems. These complex and dynamic interactions are especially relevant in autoimmune diseases of the CNS such as multiple sclerosis (MS). Using broad technical expertise ranging from molecular biological, immunological and electrophysiological methods to animal experiments in disease models and blood and tissue samples from patients with multiple sclerosis, we are specifically interested in:
Ion channel mediated regulation of immune cell and CNS functions
Ion channels are ubiquitous signal integrators regulating basic cellular functions mandatory for key pathways in autoinflammatory conditions such as immune cell activation, effector functions, demyelination and neuronal cell death. Our focus is on two-pore domain (K2P) potassium channels, the latest discovered group of potassium channels, comprising 15 members with unique expression profiles, regulation and biophysical properties.
Regulation of immune cell migration into the CNS
Migration of immune cells into the CNS tissue is a multi-step process dependent on an interaction between leukocytes and endothelial cells of the blood-brain barrier. This process is especially relevant in multiple sclerosis as has become evident from clinical practice. We have recently discovered that KCNK2, a member of the K2P channel family, regulates the inflammatory phenotype of endothelial cells opening up novel research directions on the blood-brain barrier.
Therapeutic translation of immunophysiology
The therapeutic landscape of multiple sclerosis is rapidly evolving due to the development of novel, highly specific immunomodulatory therapies. A better understanding of the biological mode of action of preclinical and clinical concepts for treatment of MS is necessary to ensure optimal treatment selection and monitoring of treatment efficacy and side effects. A close connection to patient care in the Department of Neurology enables us to address patient-oriented research questions.
Bittner, S., Bauer, M. A., Ehling, P., Bobak, N., Breuer, J., Herrmann, A. M., Golfels, M., Wiendl, H., Budde, T., and Meuth, S. G. 2012. The TASK1 channel inhibitor A293 shows efficacy in a mouse model of multiple sclerosis. Exp Neurol 238: 149-155.
Bittner, S., Bobak, N., Herrmann, A. M., Gobel, K., Meuth, P., Hohn, K. G., Stenner, M. P., Budde, T., Wiendl, H., and Meuth, S. G. 2010. Upregulation of K2P5.1 potassium channels in multiple sclerosis. Ann Neurol 68: 58-69.
Bittner, S., Meuth, S. G., Gobel, K., Melzer, N., Herrmann, A. M., Simon, O. J., Weishaupt, A., Budde, T., Bayliss, D. A., Bendszus, M., and Wiendl, H. 2009. TASK1 modulates inflammation and neurodegeneration in autoimmune inflammation of the central nervous system. Brain 132: 2501-2516.
Bittner, S., Ruck, T., Schuhmann, M. K., Herrmann, A. M., Moha ou Maati, H., Bobak, N., Gobel, K., Langhauser, F., Stegner, D., Ehling, P., Borsotto, M., Pape, H. C., Nieswandt, B., Kleinschnitz, C., Heurteaux, C., Galla, H. J., Budde, T., Wiendl, H., and Meuth, S. G. 2013. Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS. Nat Med 19: 1161-1165.
Ehling, P., Cerina, M., Budde, T., Meuth, S. G., and Bittner, S. 2015. The CNS under pathophysiologic attack--examining the role of K(2)p channels. Pflugers Arch 467: 959-972.