The cellular diversity of the human brain is immense, which is generated through evolutionarily conserved developmental mechanisms. Neural stem cells (NSCs) are on top of the neural hierarchy and need to give critical cell fate choices to generate the adult brain through various cellular differentiation trajectories. Specialized microenvironment (niche) of the adult human brain contain NSCs lifelong. Whether neurogenesis is ongoing in the adult human brain remains controversial, however, their presence raises hopes for regenerative medicine approaches. This stem-cell based system is robust enough to create a functional masterpiece, yet is susceptible to failure that may lead to cognitive dysfunction and disease. A marginal example is Glioblastoma Multiforme (GBM) that likely originates from malfunctioning adult human NSCs.
My ambition is to discover the molecular mechanisms regulating the function of NSCs using a holistic, systems biology approach. I believe this curiosity-driven research will lead to new treatment strategies for neurodevelopmental disorders and gliomas as well as their use for regenerative purposes following neurodegeneration.
The research in my lab focuses on understanding how neural stem cells integrate niche signals and epigenetic changes with their cell fate choices to build a healthy brain, and how this is lost in the context of glioma.
This research can be described in 3 questions:
- Can we reconstruct the neural lineage trajectories at a single cell level?
- How do the epigenetic changes affect cell fate choices of the developing and adult NSCs?
- How are the niche signals, lineage trajectories and epigenetic marks dysregulated in the human glioma stem cell niche?