Evolutionary trajectories in pediatric GBM
Our manuscript on genomic evolution in pediatric GBM was accepted for publication in Cancer Research and is now available on the journal website.
This project was led by Mary Hoffman, an MSc student in my lab. Her work showed that pediatric GBM harbors many genetic subclones – basically each tumor contains many mini-tumors, each with their own specific genomes.
In addition, our results indicate that pediatric GBM may be driven by populations of slow-cycling cancer stem cells. Because they do not divide very often, these cancer stem cells may be able to escape chemotherapy and radiotherapy during treatment, and may be responsible to re-grow the tumor at relapse.
Overall, Mary’s work showed that pediatric GBM is a complex ecosystem populated by cells with different genomes and functional properties, clearly challenging long-held views that postulated childhood cancers are relatively homogeneous malignancies.
Future efforts in our lab will be aimed at identifying new therapeutic opportunities that specifically target the slow-cycling cancer stem cell populations.
Two preprints from our lab are on bioRχiv
- Johnston et al. High-resolution structural genomics reveals new therapeutic vulnerabilities in glioblastoma.
- Hoffman et al. Subclonal architecture, evolutionary trajectories and patterns of inheritance of germline variants in pediatric glioblastoma.
Our research interests
Our Lab studies the epigenomes of pediatric and adult brain tumors. Our interest in the epigenome stems from our discovery that chromatin architecture specifies cell behaviour, including the key cancer property known as self-renewal. Self-renewing cells are thought to be the root cause of tumor recurrence, because they can contribute to propagation of the malignant cell population indefinitely.
In our Lab, we use patient-derived primary cultures and xenografts as model systems. These platforms can be used effectively to gain significant new knowledge on tumor biology, and as pre-clinical tools for personalized medicine.
Our academic affiliations
Departments of Physiology & Pharmacology, Biochemistry & Molecular Biology