Ongoing projects

Role of Structural Lipids and their Transporters in Alzheimer Disease and Neuropsychiatric Disorders 

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

We study the role of lipids and their transporters in the early inflammatory process of neurodegenerative diseases. In particular, we investigate the function/dysfunction of danger signal molecules, e.g. serum amyloid P component and the ceramide transporter.  Our team is leading a consortium funded by Memorabel/ZonMW studying the role of sphingolipids in AD. (https://www.sphingo-aid-memorabel.com)

Additionally, we collaborate with expert industrial- and academic partners in analytical technologies and health sciences in the Euregion (Interreg-Eurolipids). Recent findings have highlighted the importance of altered lipid metabolism in neurological disorders and evidence is mounting to support a key role of altered lipid profile. By using advanced lipid imaging technology we are investigating how lipid distribution throughout the brain is altered upon neurological disease onset and following therapy. This is critical to elucidate the effect of therapy on the brain lipidome and to identify diagnostic chemical patterns within the heterogeneous environment of the brain.
Together, we focus on the prediction and prevention of lipid-related diseases like cancer, cardiovascular-, and brain disorders. Furthermore, we aim to understand the exact role of ceramide transfer proteins and their relationship with inflammatory processes in the brain (Hersenstichting).

 
Autoimmune factors in Psychosis, Schizophrenia and Depression 

(ZonMW, Hersenstichting, NWO subsidienummer Aspasia: 015.011.033)

We aim to develop new methods to diagnose psychosis with autoimmune origin in order to enable specific immunosuppressive treatment of patients. These methods include a cell-based assay where human kidney cells are expressing the relevant target proteins and brain slices where binding of autoantibodies to intact neurons and non-nervous cells is analyzed. (http://www.psyantib.com)

 
Myasthenia gravis and related Neuromuscular Diseases

(MG project: Association fran├žaise 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.