Nicholas Mikolajewicz is a postdoctoral researcher at the Terrence Donnelly Centre for Cellular and Biomolecular Research at the University of Toronto. He is a recipient of the William Donald Nash Brain Tumour Research Fellowship, and we are proud to support his work and recognize his dedication to helping end brain tumours.

Read more about his exciting new project, “Identifying transcriptional drivers of glioblastoma heterogeneity.”

Brief summary of research:

Glioblastoma multiforme (GBM) remains an incurable brain cancer, largely due to its ability to transition and co-exist between multiple distinct states within individual patient tumours. Resistant GBM subpopulations are capable of evading immunotherapy and result in aggressive recurrent tumours with poor clinical outcomes. This project will use a combination of bioinformatic and genetic tools to identify gene expression regulators in GBM cells (i.e., transcription factors) that enable the reprogramming of heterogeneous GBM tumours into uniform states that are responsive to immunotherapy.

Candidate transcription factors that control the transition of GBM between different cell states will be identified using (i) a combination of single-cell transcriptomics and bioinformatics to map GBM-subtype-specific gene expression patterns to known gene regulators, and (ii) genome-wide CRISPR screens to identify genes that influence GBM immune resistance. GBM cells will then be genetically engineered to disrupt the functions of candidate transcription factors, thereby identifying specific genetic perturbations that reprogram GBM cells into uniform cell states for each GBM subtype. Ultimately, the growth of reprogrammed GBM tumours in mice receiving tumour-targeting T-cell transfers will be evaluated. This work will provide novel insights into the drivers of GBM heterogeneity and explore whether reprogramming GBM tumours can improve immunotherapy outcomes.

What receiving this award means to Nicholas:

Being awarded the William Donald Nash Brain Tumour Research Fellowship will allow me to develop an exciting project on glioblastoma that addresses one of the greatest challenges in cancer treatment: how do we treat something that actively evades conventional and emerging therapies? Emerging single-cell genomic technologies make this an exciting time for cancer research, as they provide tools to glimpse tumour heterogeneity and complexity at unprecedented single-cell resolution. Over the term of this fellowship, I will develop and apply these technologies to identify novel molecular targets that will reprogram glioblastomas to different states, with the aim of sensitizing these tumours to existing and emerging treatments. As a postdoctoral fellow, this fellowship is an incredible opportunity to develop my own ideas and apply my interdisciplinary training in statistics, cellular biology, and single-cell genomics to the complexities of glioblastoma. As a medical student, my excitement for this project cannot be overstated, as the support of this fellowship sets the stage for me to develop my eventual findings into novel and exciting therapies as a clinician-scientist. I am grateful to the Nash Family and the Brain Tumour Foundation of Canada for this generous opportunity and for supporting my aspirations towards becoming a clinician scientist.