Ongoing projects

Role of Structural Lipids and their Transporters in Neuropsychiatric Disorders. Targeting Lipids to Diagnose and Treat disease.

(ZonMW-Memorabel, Weston Brain Institute, Hersenstichting (immunotherapy and PET)

Recent studies point to the role of lipids in inflammation in neurodegenerative diseases such as Alzheimer’s disease (AD). The metabolism of certain lipids could be changed and be part of the early disease process. Our research group aims to understand the effect of membrane lipid dysregulation in disease onset and progression. Current knowledge supports the hypothesis that targeting this pathway may be beneficial to slow down or even stop disease development.
We have tested with our team several putative treatment strategies, which together demonstrate that modulation of this lipid pathway can modify the pathophysiology in animal models for AD. We plan to clarify the molecular pathways involved to fine-tune our targeted strategy in the coming years.
Additionally, we are exploring the possibility that some of these lipids can serve as biomarkers of neurodegenerative/neuropsychiatric diseases.

 
Autoimmune factors in Neurological, Psychiatric and Neuropsychiatric Disorders. Improvement of Diagnosis and Treatment.

(ZonMW, Hersenstichting, NWO subsidienummer Aspasia: 015.011.033)

Recent data point to the occurrence of autoantibodies in subgroups of patients in neuropsychiatric disorders, including data shown by our group. Currently, for this new type of autoimmune disorders of the CNS improved diagnosis and treatment strategies are being investigated. Our work clearly shows that known autoantibodies present in autoimmune encephalitis are not present in chronic patients with psychotic disorders. We are currently investigating other groups of mental disorders.  
Additionally, efforts are being made to understand the role of autoimmune antibodies against specific targets, e.g. at the neuromuscular junction. In this research line, new strategies for immunosuppression are being investigated. We have recently started a collaboration with Prof. Rene Hout to work in checkpoint inhibitors in myasthenia gravis (MG). Additionally, studies are initiated with Washington University to search for treatment response biomarkers. Moreover, the role of the thymus in autoimmunity is currently a focus from this research line for the next years since MUMC+ is a center of excellence for thymectomies.
Finally, new animal models of MG are being developed in collaboration with Yale University.”

 
Myasthenia gravis and related Neuromuscular Diseases

(MG project: Association française contre les Myopathies, AFM-20851)  

In MG we are investigating the possible use of proteasome inhibitors for targeting autoimmune long-living plasma cells. These plasma cells are resistant against broad-range immunosuppressants and since they keep producing autoantibodies this is a major problem in the current treatment of MG and other antibody-mediated autoimmune diseases. Plasma cells depend on their proteasome to sustain high-rate protein synthesis. Consequently, proteasome inhibitors have the capacity to kill plasma cell by inducing accumulation of the terminal unfolded proteins that ultimately are lethal for these cells. In a variant of MG caused by antibodies against the synaptic protein MuSK we aim to provide a human recombinant monoclonal MuSK autoantibody. This enables us to study the pathogenic mechanisms. Here we also aim to find the cellular B cell subset responsible for the production of MuSK autoantibodies which may identify therapeutic targets for a tailored therapy.