Generously funded by The Frazer Anderson Pediatric Research Grant, funded by Acuitas Therapeutics Inc.

Alan Underhill – University of Alberta, AB

Project Title: “Determinants of KMT5B dysfunction in pediatric glioma”

Description of Project:

Gliomas are a type of brain cancer and represent the most common solid tumor type seen in children. Although adults get these cancers with lower frequency, they are fundamentally different at the molecular level. Specifically, the types of DNA mutations that occur in these tumors in children are not the same as those in adults, suggesting the disease process is different and will likely require different approaches for treatment. In this proposal, we use multiple microscopy approaches to visualize cells from these childhood gliomas with the goal of understanding how their unique mutations cause this devastating disease. This knowledge can be applied to identifying strategies that enhance the utility of current treatments such as radiation therapy.

What receiving this award means:

“The funds received from the Brain Tumour Foundation of Canada will allow us to build on exciting preliminary results and are critical to sustaining longer term studies aimed at evaluating clinical utility in childhood brain cancers.”

October 2023 – Update

With funding from the Brain Tumour Foundation of Canada, we have been able to carry out more detailed studies of the KMT5B protein. At the same time, other research has identified additional KMT5B mutations in both pediatric and adult gliomas that reinforce its role in tumour progression. One of our initial premises was that the differences in the cellular environment created by glioma alter what KMT5B does and where it goes within tumour cells. To that end, we have found that KMT5B can occupy several discrete locations within glioma cells and identified a ‘molecular switch’ that accounts for how the protein moves between two of these locations. We have also gained some understanding of how the on/off state of this switch is controlled. With our remaining funding on this grant, we hope to test ideas on how this switch may aberrantly function in glioma.