Magdalena is a highly talented Master's student in the Master program Neuroscience at the University of Vienna. She is performing reprogramming of patient-derived PBMCs and establishes regionally specified brain organoids (forebrain and hindbrain) from our patient-derived iPSCs.

She has been able to show that patient-derived forebrain organoids develop hyperproliferative zones and tumor-like lesions, while at the same time displaying a dysintegration of rosettes. She will assess whether brain organoids with distinct regional patterning show different dynamics in tumor initiation. Furthermore, she will perform molecular profiling of patient-derived organoids and compare the results to profiles obtained from patient tumor biopsies.

Elena is a trained neurologist and currently obtaining her Master's degree in Molecular Precision Medicine at the Medical University of Vienna. With rigor and precision, she has established an applicable workflow for rapid methylation-based brain tumor classification using nanopore sequencing.

Elena's work has brought cutting-edge rapid molecular diagnostics to application in our Division. In a streamlined workflow using random genome-wide sequencing on a MinION device, she has implemented brain tumor classification in 8-24h (depending on the reusage performance of the flow cell). In a next step, Elena aims to achieve intraoperative ultra-fast classification, obtaining results within 90min. Additionally, she will establish adaptive sampling to specifically screen therapy-relevant loci, such as the MGMT promoter or the BRAF gene.

Eviana is a Master's student from the University of Cologne, who performed pluripotency validation in one of our patient-derived iPSC lines. She could also show comparable behavior of healthy donor-derived iPSCs and patient-derived iPSCs in terms of proliferation rate, expression of pluripotency markers and ability to give rise to cerebral organoids.

Maximilan attends Med School at the Medical University of Vienna. He has performed histological stainings for H3K27me3 on human fetal cerebellar tissue, where he observed dynamic, cell type-specific changes in H3K27me3 levels in the course of cerebellar development. He also became interested in a rare cerebellar malformation called rhomboencephalosynapsis, which shows distinct H3K27me3 levels.

The characterization of distinct cell types in human fetal brain malformations is surprisingly superficial. In order to overcome this knowledge gap, I am making use of my knowledge on particular cell type markers to visualize the various progenitor, neuron, and glia populations in fetal tissue archived in the impressive neurobiobank at the Division of Neuropathology and Neurochemistry at MedUniWien.

The resulting detailed description of cellular alterations in distinct malformations, such as hemimegalencephaly, will be highly valuable to the community as important reference for experimental models besides awareness about our biobank for research purposes.

Happy to collaborate!

GW22 hemimegalencephaly

In order to assess the function of the epigenetic regulator Polycomb Repressive Complex (PRC)2 in human brain development, we are applying immunohistochemistry stainings for H3K27me3 to human fetal brain FFPE sections. This approach allows us to monitor PRC2 dynamics across developmental stages and cell types in the human brain. Starting in the cerebellum, we observe H3K27me3 loss in the IGL over time, correlating with granule cell development. In contrast, we detect retainment of high H3K27me3 levels in the Purkinje cell layer.

In a rare cerebrallar malformation termed rhomboencephalosynapsis, where the vermis is completely missing and the cerebellar hemispheres are fused, we see higher H3K27me3 levels in the IGL as compared to age-matched controls. This rather immature state correlates with an immature appearence of Purkinje cells, potentially indicating an overall immature state of the cerebellum in the malformed condition.

Human fetal cerebellum: comparison of H3K27me3 levels in control and rhomboencephalosynapsis