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. (link to memorable Website)

 
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.