Science
Our research is focused on molecular neurobiology in the context of severe mental disorders, including bipolar disorder (BD), schizophrenia (SCZ) and major depression (MDD). In specific we are interested in how disturbances in the development of neural networks lead to manifest psychiatric illness. Family based studies have revealed high heritability in primarily SCZ and BD (up to 80%) and thus genome-wide association studies have resulted in multiple associated SNPs. One of the repeatedly found SNPs lie in the intronic region of the calcium channel gene CACNA1C. We have multiple iPS lines of both healthy controls and BD patients with known variants of this SNP. We are also interested in potential splice variants of CACNA1C and try to find novel variants together with professor Paul Harrison in Oxford and Pantazis group at Linköping University.
We are also planning for harvesting skin cells from SCZ patients. As BD and SCZ show strong similarities with regards to genetics and partially also clinic, we plan to compare iPS derived neurons from SCZ with BD patients. One line of research is looking at rare risk genes for SCZ using CRISPR in both neuron/glia cultures and in placenta. In collaboration with Dr Gianluca Ursini at the Lieber Institute for Brain Development we develop placenta organoids to study how this model could be used to understand early risk factors. In order to increase the phenotypic precision, we aim at developing new methods for deep phenotyping using clinical data. One potential way of stratifying patients is how they respond to different treatments. For instance lithium responders in BD are thought to constitute a rather homogeneous population. We are running one project in treatment response in MDD using iPS cells. This is in collaboration with professor Johan Lundberg at the Karolinska Institutet, who is PI of a psilocybin study.
iPS cells are differentiated to neurons and glia using both 2D and organoid cultures (see images below). We perform both molecular based (RNAseq, CRISPR) and functional assays (calcium imaging, MEA, optogenetics). We also develop pipelines for image analysis to quantify for instance the dendritic tree.
One recent line of research involves diving into the field of cancer neuroscience. We want to understand neural networking processes among healthy cells and glioma cells. This is in collaboration with the neurosurgery professor Asgeir Jakola at GU as well as professor Frank Winkler in Heidelberg.
Please see publications for more detailed information on previous work.
