Human Brain Disease Modelling (Lehtonen lab)

Research group

Our research focuses on revealing the cellular and molecular mechanisms of neurological diseases, especially Parkinson`s disease (PD). We utilize patient-derived brain cells in novel human-based models, including 3D culture systems and midbrain organoids, to more accurately mimic the diseased brain’s pathological conditions. We are especially interested in the glial non-cell-autonomous mechanisms and their contribution to the degeneration of dopaminergic neurons. We use breakthrough single-cell and imaging technologies combined with bioinformatics to reveal the mechanisms and identify key therapeutic targets and pathways responsible for PD’s pathological glial phenotype.

Funder(s)

Main funder

Jane and Aatos Erkko Foundation

Other funders

Sigrid Juselius Foundation

Päiviki ja Sakari Sohlberg Foundation

Business Finland

The Finnish Parkinson Foundation

The Finnish Culture Foundation

We are also interested in building up a human organ-on-chip model for the blood-brain barrier (BBB) as the BBB and drugs’ ability to cross the BBB and reach the correct target is critical when designing drugs for neurological diseases. To this end, we utilize stem cell-derived human endothelial cells, astrocytes, and pericytes and combine them with organ-on-chip technology. The use of all human cells omits problems arising from cross-species differences, and the organ-on-chip technology mimics the physiological architecture of the BBB and fully control the cellular microenvironment. The chips are provided by Finnadvance – an Oulu-based startup company. Our goal is to use the BBB chips for testing novel drugs and biomolecules like extracellular vesicles to penetrate the BBB. We are also interested in using the model to uncover the molecular and transport mechanisms that regulate BBB permeability in physiological and pathological conditions.

Homepage of the group

Keywords

astrocytes blood-brain barrier dopaminergic neurons endothelial cells humanised mouse models iPSC microfluidics microglia midbrain organoids neurons organ-on-chip Parkinson's disease pericytes psychopathy schizophrenia