The ‘Neuro-Aging’ team focuses on glutamate transport, with emphasis on system xc - , in health and disease. We have ongoing projects on the role of system xc - or the cystine/glutamate antiporter in e.g. Parkinson’s disease, Alzheimer’s disease, and (central effects of) (pancreatic) cancer. In most of these projects, neuroimmune communication is receiving increasing attention. Our overall hypothesis that inhibition of system xc - might be a therapeutic strategy to treat (age-related) diseases that are characterized by excitotoxicity and neuroinflammation, also necessitates research towards the importance of system xc - in normal (healthy) brain functioning. As such, we are investigating how system xc - regulates glutamatergic transmission and plasticity under physiological conditions. Finally, we study the involvement of system xc - in the process of brain aging, how this is impacted by peripheral immune senescence and by age-induced shift in cellular energy metabolism. To increase the translational value of this research, we actively search for novel strategies to target system xc -.

Research within the ‘Viro-Immunotherapy’ team can be divided in two parts: the first part focuses on the development of novel immunotherapeutic approaches for the treatment of HIV infections. We have a longstanding expertise in this field, with a special focus on raising strong T cell responses to keep the virus at bay. Starting with in vitro generated autologous dendritic cell vaccines, we are now investigating mRNA and self-replicating RNA packaged by state-of-theart nanoparticle systems for optimal delivery in patients. A longstanding collaboration with prof. Sabine Allard of the UZ Brussels ensures access to relevant patient samples and offers the possibility to set-up investigator driven (often first in human) clinical trials. A major bottleneck for this type of research is the presence of a latent reservoir, consisting of resting immune cells that harbor the HIV virus in their genome. The possibility to target latently infected cells by stimulating various aspects of the immune system, with a special focus on natural killer cells, is being investigated. Collaborators include: Guido Vanham and Kevin Ariën, ITM, Linos Vandekerckhove, UGent; Rob Gruters, RESEARCH & DATA MANAGEMENT 4 Erasmus MC Rotterdam; Felipe Garcia, Hospital Clinic Barcelona. The second part of our research is focused on immunogenic cell death in cancer cells and how this can contribute to enhanced anti-tumor responses. Viruses have the unique capacity to outsmart tumor cells by exploiting mechanisms that are used to transform normal cells (e.g. a reduced type 1 interferon production capacity). Based on this principle so-called oncolytic viruses, can replicate exclusively in tumor cells, but not in healthy cells. We want to explore how oncolytic viruses can be modified in order to increase immunogenic cell death, thus enhancing their anti-tumor immune responses. A collaboration with prof. Bart Neyns of UZ Brussels ensures access to relevant samples and material. Other collaborators include: B. van den Hoogen, Erasmus MC Rotterdam and Iain McNeish, Imperial College, London. Recently, the Aerts team, together with the Infectious Disease department of UZ Brussels started to collect samples from COVID-19 patients. Using our extensive immunological expertise, we will analyze these samples and hope to learn which immunological phenomena contribute to disease but also to protection.