Metabolic Interactions and Transport across the Neurovascular Unit

The neurovascular unit is a gate-keeper of the central nervous system. We aim to study the metabolic changes of the neurovascular unit under steady state and under stimuli of neuropsychiatric drugs, known to have metabolic side effects.

We use stem cell-derived Organ-on-a-Chip models to re-create the human blood barrier function, both in terms of passive permeability and relevant transporter functionality. This model serves to predict blood-brain-barrier passage of novel drugs and known toxicants and the possible drug-drug interactions effecting transport event. Moreover, we are also using micro-engineering to build up a holistic model of the neurovascular unit also integrating interactions with models of neuronal tissue. Specifically, we use this model as a tool to study the metabolic interplay in-between the constituting cells by evaluating transcriptomic and proteomic profiles in combination with targeted and untargeted mass spectroscopy to study metabolic signatures.

The Organ-on-a-Chip models allows for integration of all from vascular endothelial cells to functional neuronal cells, not possible in static cultures while giving a temporal and spatial resolution not doable in vivo.