WEHI Brain Tumour Research Group Special Seminar hosted by Dr Sarah Best

Dr Akram Hamed

Department of Molecular Genetics – University of Toronto, Canada

Single-cell mapping of gliomagenesis reveals links to neural crest and injury response programs

L7W Seminar Room

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Including Q&A

Dr Hamed received his PhD in Molecular Genetics from the University of Toronto. His research focuses on studying malignant gliomas and understanding how these brain tumours initiate and progress. He also studies normal brain development and tissue regeneration, focusing on the links between these processes and the development of brain cancers. His work revealed the mechanisms that drive the development of malignant gliomas from mutant cell populations, as well as the role of the brain microenvironment and injury programs in regulating the early stages of tumour formation. Dr Hamed has several publications in high impact journals and his work contributed to the understanding of brain development and brain cancer biology. 

Glioblastoma is an incurable brain malignancy. By the time of clinical diagnosis, these tumours display a degree of genetic and cellular heterogeneity that provides few clues to the mechanisms that initiate and drive tumourigenesis. To explore the early steps in gliomagenesis, we utilized conditional gene deletion and lineage tracing in tumour mouse models, coupled with serial magnetic resonance imaging to initiate and then closely track tumour formation. We isolated labeled and unlabeled cells at multiple stages — before the first visible abnormality, at the time of the first visible lesion, and then through the stages of tumour growth — and subjected each stage to single-cell profiling. We identify a malignant cell state with a neural crest-like gene expression signature that is highly abundant in the early stages, but relatively diminished in the late stage of tumour growth. Genomic analysis based on the presence of copy number alterations suggests that these neural crest-like states exist as part of a heterogenous clonal hierarchy that evolves with tumour growth. By exploring the injury response in wounded normal mouse brains, we identify cells with a similar signature that emerge following injury and then disappear over time, suggesting that activation of an injury response programme occurs during tumourigenesis. Indeed, our experiments reveal a non-malignant injury-like microenvironment that is initiated in the brain following oncogene activation in cerebral precursor cells. Collectively, our findings provide insight into the early stages of glioblastoma, identifying a unique cell state and an injury response programme tied to early tumour formation. These findings have implications for glioblastoma therapies and raise exciting new possibilities for early disease diagnosis and prevention. Hamed, A. A. et al. Nature 638, 499-509 (2025).

All welcome!