Research Studentship - Ashley Adile

Ashley Adile is an Undergraduate Science Student at McMaster University

Ashley's project has been generously supported by a gift from the Taite Boomer Foundation

Progress Report

To date, dose response curves, western immunoblotting, RT-qPCR, secondary sphere formation, limiting dilution and cell cycle analysis assays were employed to functionally investigate the effects of small molecule inhibitors against Bmi1. Collectively, the multitude of in vitro experiments demonstrated the ability of Bmi1 inhibitors to significantly diminish Bmi1 activity in medulloblastoma. A loss in Bmi1 expression levels have shown increased sensitivity to ionizing radiation, rather than resistance - typical of BTICs. This insinuates that decreased Bmi1 protein levels may circumvent challenges of current therapeutic modalities for treatment of pediatric MB. With Group 3 MB patients limited to palliation, novel Bmi1 inhibitors show promise to selectively target the driving clonal populations. Additionally, dose response curves were generated in our Group 3 MB stem cell lines with various Stat3 inhibitory agents, generously provided by our collaborator from the University of Toronto. One such compound was found to be a potent inhibitor of histone deacetylase, which is thought to impede on the survival of cancer cells. A publication for this small molecule inhibitor is in preparation. Future work will consist of in vivo validation of the inhibitor with the greatest in vitro efficacy in our established mouse adapted patient-derived therapy models.

About the research

Project:”Small molecule inhibitors targeting self-renewal as a therapeutic option for recurrent childhood medulloblastoma”

As the most common malignant pediatric brain tumour, medulloblastoma (MB) remains one of the leading causes of childhood cancer mortality. Its aggressive nature has recently been attributed to a rare cell population termed brain tumour-initiating cells (BTICs). BTICs alone can drive tumour formation and lead to poor outcomes by escaping available radio-chemotherapy regiments. MB patients who have relapsed hold the worst clinical prognosis, as they are limited to palliation due to a paucity of clinical trials using targeted approaches. In our work, we have identified novel therapeutic targets, Bmi1 and STAT3, both of which play an important role in MB development and metastasis. Our early experiments have identified small molecule inhibitors that can effectively reduce levels of both targets and prolong survival in preclinical models. The main objective of the proposed study is to discover new opportunities for treating the most aggressive type of brain cancer affecting children, and thus not only improves the quality of treatment received by the children, but also the overall survival of patients with MB.

About Ashley, in her own words...

Research Student -  Ashley Adile, Undergraduate Science Student, McMaster UniversityBeing awarded a Brain Tumour Research Studentship means the opportunity to continue my life motto that “the learning never stops”, allowing me to pursue valuable work in medulloblastoma research. This recognition strengthens my commitment towards a career in medicine, in hopes of making a meaningful contribution towards finding a cure for those impacted by this debilitating disease. I am both honoured and humbled by this studentship and sincerely thankful to Brain Tumour Foundation of Canada, its generous donors and patients who nobly donate their tumour samples to make this research possible. I am grateful for the opportunity to work alongside Dr. Sheila Singh and her lab of innovative scientists.

They, along with the patients through my volunteer work at McMaster Children’s Hospital and Ronald McDonald House Charities South Central Ontario fuel my motivation, making it a privilege to explore such novel work over the next two summers and beyond. 

As a recipient of this research studentship I aspire to further progress and make a difference in pediatric brain cancer research. I hope that one day I will make Taite and his family, who graciously funded this award, proud knowing how his life gave meaning to the world.

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