Medical Scientist-Programm 2025

Thema: "Developing a synthetic stem cell model to decode gliomagenesis mechanisms in human brain organoids"

Zusammenfassung:
Glioblastoma multiforme (GBM) is the most debilitating cancer of the human brain. GBM includes glioma stem cells (GSCs) resistant to chemotherapy and radiation. Somatic mutations in several tumor suppressor genes contribute to high inter- and intra-tumoral heterogeneity, ultimately leading to the co-evolution of various GSC types through clonal extinction and divergence at the later stage. Therefore, dissecting the early events of gliomagenesis in a disease-relevant context is crucial. Additionally, current GBM research heavily relies on patient
biopsies, which are limited by sample quantity, feasibility of further culturing, and ethical challenges. An alternative is the murine model, but it is expensive, time-consuming, unsuitable for drug screening, and may not accurately reflect relevant brain biology. Consequently, it is
critical to develop a synthetic stem cell model that recapitulates the initial events of gliomagenesis and allows for drug testing in a human brain tissue-like environment. To achieve this, I will establish engineered neural stem cell models, “pre-Glioma Initiating
Cells (Pre-GICs)” where the key tumor suppressors TP53, PTEN, and NF1 can be spatiotemporally inactivated. Generating 3D human brain organoids from Pre-GICs will mimic GBM characteristics in a brain-like environment and facilitate drug discovery studies.