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Project

Development and preclinical assessment of a multiplex, single-cell, protein-based assay for functional drug screening of glioblastoma

Glioblastoma (GBM) is the deadliest brain tumor, and remains, to date, largely incurable. GBM’s poor prognosis has been attributed to a broad heterogeneity occurring not only between different patients, but also within each tumor. The diversity and complexity of this disease suggests a need for more personalized treatments, which is not being met by current standard-of-care. In this project, I will overcome this issue by directly evaluating the sensitivities of single tumor cells to potential treatments at an unprecedented resolution. To do so, I will develop so-called functional diagnostic assays using mass cytometry by time-of-flight (CyTOF) through which the molecular effects of therapy will be measured in patient-derived cell lines and freshly resected ex vivo tumor samples upon drug exposure. As I have demonstrated in pilot experiments, this approach will enable me to differentiate tumor cell subpopulations which react differently to particular treatments, providing a rational explanation of why clinical trials have not been more successful so far, and supporting a novel framework to develop precise selections of treatments in a more personalized way. Subsequently, I will test the diagnostic value of my approach by using mouse models of GBM to assess whether CyTOF-based treatment recommendations provide survival benefits as opposed to non-personalized treatment regimes.

Date:15 Sep 2018 →  31 Dec 2019
Keywords:CyTOF, Proteomics, Glioblastoma
Disciplines:Morphological sciences, Laboratory medicine
Project type:PhD project