Hypoxia-driven spatial dynamics of transcriptional and epigenetic cell states in glioblastoma

Mapping glioblastomas to better understand the role of hypoxia in tumour heterogeneity 

Glioblastoma (GBM) is one of the most aggressive and treatment-resistant cancers, in part because of the incredible diversity found within each tumour. Now, with support from the 2025 Marathon of Hope Health Informatics and Data Science Award, Phoebe Lombard (Princess Margaret Cancer Centre) will investigate how a powerful force may be shaping this diversity from within: oxygen. 

As tumours grow, they often develop regions with dramatically different oxygen levels. These oxygen gradients—or areas of low oxygen (hypoxia) and high oxygen—can influence how cancer cells behave, pushing some to become more invasive, more resistant to therapy or better able to evade the immune system. But exactly how oxygen levels affect the gene activity and identity of different GBM cell types remains poorly understood. 

As part of her project, Lombard will use cutting-edge spatial multi-omic profiling to map where different subtypes of GBM cells appear within a tumour and how those locations correlate with oxygen levels. She and her team will then analyze tumour samples from patients and conduct follow-up studies in mouse models to determine how altering oxygen availability impacts tumour composition. Ultimately, her goal is to uncover the molecular mechanisms—particularly oxygen-sensitive enzymes—that drive GBM cell diversity. 

By revealing how something as fundamental as oxygen influences tumour behaviour, Lombard’s work could lead to new therapeutic targets—and fresh hope—for patients facing this devastating disease. 

“I am thrilled and so grateful to be amongst the recipients of the Marathon of Hope Health Informatics and Data Science Award this year,” said Lombard. “This award will enable my team and I to employ the most cutting-edge spatial multi-omic profiling techniques in our patient cohort — the results from which will help us to uncover how the gene regulatory landscape changes throughout the tumour in glioblastoma.” 

Funding envelope 

As part of the Health Informatics and Data Science Award, Lombard will receive $40k over the next year from the Network, which is matched by her host institution for a total envelope of $80k. 

Her mentor, Dr. Brad Wouters, emphasized the project’s importance: 
“I am extremely excited about the potential of the project funded by the Marathon of Hope Health Informatics and Data Science Award to Phoebe Lombard. Her project will tackle the challenges of biological diversity within glioblastoma that are responsible for treatment failure and disease progression.”