While animal studies are invaluable for understanding brain functions, animal models translate poorly to humans. This is largely due to fundamental differences in complexity and functional capacity between rodents and humans. Human brain shows also genetic variability and sensitivity to environmental factors. It is thus challenging to analyze molecular mechanisms of genetic and environmental factors in brain diseases, and develop preventive measures or therapies.
Our aim is to understand the impact of genetic and environmental factors in human brain cells of major brain diseases prior to disease onset and develop tools for predictive medicine and therapy.
We use iPS cells representing neurological and psychiatric diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia (SCZ) and psychopathy. Differentiation of iPSCs into neurons, astrocytes and microglia allow us to analyze aberrant gene and protein expression, function and metabolism in developing and maturing human brain well before the disease onset. The interplay between different cell types is analyzed in 3-dimentional cultures systems and by transplanting these cells into the mouse brain. Our models can be exposed to various environmental risk factors and brain insults. We also combine endothelial cells, pericytes and astrocytes for modelling blood-brain barrier. The impact of mutations and potential therapeutic genes are tested by using CRISPR/Cas9 system, gene transfer and novel small molecules.
Neurons, astrocytes and microglia show aberrant transcriptomic and protein expression profiles and have strong phenotype in several brain diseases, and that molecular mechanisms of brain diseases are partially sex-specific.