Glioblastoma (GBM) is the most common and deadly form of adult brain cancer, with only 2-3% of patients surviving more than five years after diagnosis. One defining feature of GBM is a leaky, tortuous, and abnormally functioning vasculature. Significant time and resources have been devoted to developing drugs that block blood vessel growth in GBM, but these investments have yielded no improvements in overall survival. One reason for this lack of efficacy is a diverse tumor vasculature, as the identities and properties of the blood vessel populations remain poorly defined. This is a major hurdle in the development of new treatments for this deadly disease. Therefore, the goal of this study is...

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Glioblastoma (GBM) is the most common and deadly form of adult brain cancer, with only 2-3% of patients surviving more than five years after diagnosis. One defining feature of GBM is a leaky, tortuous, and abnormally functioning vasculature. Significant time and resources have been devoted to developing drugs that block blood vessel growth in GBM, but these investments have yielded no improvements in overall survival. One reason for this lack of efficacy is a diverse tumor vasculature, as the identities and properties of the blood vessel populations remain poorly defined. This is a major hurdle in the development of new treatments for this deadly disease. Therefore, the goal of this study is to (1) define endothelial diversity in GBM and (2) understand how these diverse populations affect tumor progression in the presence of existing chemotherapies, while (3) exploring a novel therapeutic concept: targeting gene expression within the blood vessels themselves. To address these problems, we will use mouse models of GBM and compare them to primary human GBM stem cell-derived tumors to determine how blood vessel diversity affects tumor progression and response to therapy. Simultaneously, we will determine how genetic and pharmacologic inhibition of a novel transcription factor, BRD, impacts tumor vascularization and endothelial gene expression. These studies will pave the way for the generation of therapeutics to target the GBM vasculature and benefit patients.

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