Prof. Ari Waisman PhD
University Medical Center of the Johannes Gutenberg University
Institute for Molecular Medicine
Mainz | Germany
My whole scientific career is focused on the study of basic mechanisms that regulate the development of central nervous system (CNS) autoimmunity. Since the time of my first postdoc in the lab of Larry Steinman, I have been interested to study how the immune system induces damage to the CNS, focusing both on the effector immune cells as well as on the responding CNS cells. Currently, my lab consists of a unique mixture of immunologists and neurobiologists, which teams up to study immune-CNS interactions.
In the last years, my labs focus has been on understanding how immune cells convey damage to CNS cells. For that, we work with genetic tools to specifically study the blood-brain barrier (BBB), neurons and the different glial cells (oligodendrocytes, microglia and astrocytes), all being potential targets for immune attacks. We generated mice that lack the receptors for important molecules produced by the immune cells, for example, IL-1, IL-6 and IL-17. Using these unique genetic tools, we are able to appreciate the exact contribution of immune and inflammatory mediators to CNS damage. On the other hand, my lab has contributed to the advance of our understanding of the immune cells that participate in MS and its animal model, where we focused our studies on Th17 cells and regulatory T cells. Our studies also helped to understand how dendritic cells induce both pathogenic T cells and regulatory T cells, knowledge that will help us in the future reduce the pathogenic population and increase the regulatory one, to inhibit CNS autoimmunity.
I believe that this is of outmost importance to for basic but especially for translational MS research, as the data from the mouse models can be extrapolated to the human patients, since the cells involved in CNS inflammation are the same in people and mice. The discovery of how immune mediators induce damage to the CNS will allow us and others to design much more accurate therapies for the patients. Our ultimate aim is to tailor these therapies to specific molecules and even to specific cells of the CNS. This way, we can prevent overwhelming tolerance of the immune system, whereas a clever tailored therapy will only inhibit a small part of the immune system but otherwise allow it to function properly. Such a strategy should be advantageous compared to the current therapies used in MS where whole immune cellular populations are depleted or important pathways are inhibited.
In the future, we plan to translate our findings from the mouse model to the human disease. Although the EAE mouse model is different in many aspects to human MS, it can nevertheless teach us important lessons on how CNS cells respond to autoimmune attacks. We plan therefore to use the data generated from the mice and investigate if similar mechanisms occur also in MS patients, with the aim to better understand the mechanisms leading to CNS damage in MS patients, with the aim of reaching personalized therapy.