PhD defence B. (Bas) Lendemeijer

Research into the functioning of human brain cells has historically been difficult due to ethical concerns and limited availability of the primary tissue. Induced pluripotent stem cell (iPSC)-technology has created the ability to study the development of healthy and patient-derived neural cells in vitro and identify cellular phenotypes associated with certain disorders. The potential of this relatively new field has sparked great interest in the field of neuroscience and beyond. The work presented in this thesis attempts to improve the techniques to differentiate iPSCs towards cells of the neural lineage and demonstrates how these cells can be leveraged to study brain disorders. Patient-derived iPSCs are used for an in vivo preclinical screening of human antisense oligonucleotide therapy to treat Angelman Syndrome, restoring the expression of the causal gene defect in neurons. By performing genetic analysis on a family with a high incidence of schizophrenia and creating iPSCs from affected and unaffected siblings, we were able to identify a causative variant highly expressed in oligodendrocyte precursor cells, and show that these cells, when derived from patients, were less likely to mature into myelinating oligodendrocytes. The value of having quick access to iPSC-derived neural cells is demonstrated in our work with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the virus responsible for the current pandemic. Patients often experience neurological symptoms during or following infection. We show that although SARS-CoV-2 primarily infects neurons, it displays limited replication in neural cultures but does induce the production of pro-inflammatory cytokines.

The public defence will take place at the Prof. Andries Queridoroom, 3rd floor Education Center, Erasmus MC. The ceremony will begin exactly at 13.00 PM. In light of the solemn nature of the ceremony, we recommend that you do not take children under the age of 6 to the first part of the ceremony