Neurological diseases are often underpinned by inappropriate CNS immune cell reactions. Thus, their underlying cellular and molecular mechanisms have emerged as a potential therapeutic target. The Neuro-Immunology Group aims to identify the immunological properties of CNS immune cells, with microglia representing the key effector cells, as well as to investigate their crosstalk with peripheral immune cells under tumorigenic, inflammatory and neurodegenerative conditions in order to identify specific programs which could represent targets for therapeutic intervention.
1. We characterise cells at the -omics level, for instance elucidating their epigenetic, transcriptional and metabolic signatures;
2. We identify genes and pathways that are perturbed under disease conditions and compare them to homeostatic states;
3. We investigate how manipulating the identified pathways affects the acquired phenotype and eventually the disease outcome.
To reach our objectives, we take advantage of specific mouse models for brain tumours and neurodegenerative diseases as well as in vitro eukaryotic cell cultures. Lastly, we validate our findings using valuable biological samples from patients. We combine -omics analyses with specific molecular biology tools and cutting-edge biochemical assays. Additionally, we work in collaboration with bioinformaticians and computational biologists to infer the underlying networks as well as to integrate our data with existing information gathered through literature review.
On top of this systems approach, much of our attention is focused on IRG1/ACOD1, a key immune response gene expressed by myeloid cells under inflammatory, tumorigenic and neurodegenerative processes. We have previously elucidated the function of IRG1/ACOD1 protein by demonstrating that it links metabolism to immunity by catalyzing the production of the anti-microbial/anti-inflammatory metabolite itaconate from cis-aconitate in the tricarboxylic acid (TCA) cycle. Notably, our discovery contributed to pave the way to the emerging field of immunometabolism, which is currently revealing the crucial role of metabolic reprogramming in immune responses.
A better understanding of the cellular and molecular mechanisms underlying the immunological properties of CNS immune cells and the subsequent ability to manipulate them, such as render them anti-tumorigenic in brain tumours or neuroprotective under neurodegenerative conditions, is critical to us. This will pave the way to novel therapeutic applications tailored to specific neurological diseases with an immunological component.
Luxembourg Institute of Health is a public biomedical research organisation. Striving for excellence, its researchers, by their creativity, enthusiasm and commitment, generate knowledge on disease mechanisms and contribute to the development of new diagnostics, preventive strategies, innovative therapies and clinical applications that impact the healthcare of Luxembourgish and European citizens.