MAPPING SINGLE-CELL DRUG RESPONSES IN GLIOBLASTOMA USING A MULTI-OMICS APPROACH

(ref. BAP-2022-8)

Laatst aangepast : 7/01/2022

The laboratory of Precision Cancer Medicine (www.LPCM.be) is a young team within the Translational Cell and Tissue Research Unit at the department of Imaging and Pathology (KULeuven) and directly affiliated to the University Hospitals Leuven, one of the largest hospitals in Belgium and Europe. The team is led by Prof. De Smet, a Bioengineer with a PhD in Biomedical Sciences, who founded the laboratory in 2016. Our group harbors one of the largest biobanks of living and cryopreserved human brain tumor tissues and research models, derived from patients treated in our hospital and across Belgium, which are available for research. Through a close collaboration with the neuro-oncology department of the University Hospitals Leuven, this department is ideal to do translational research. Next to state-of-the-art brain tumor models, we have experience with various single-cell technologies, including CyTOF and single-cell RNA sequencing on dissociated materials or patient-derived cell lines. Finally, our group recently installed a platform for multiplexed immunohistochemistry that allows for spatially resolved, single cell analysis, for which we have now an extended team of bio-informaticians to develop the required analysis tools.

Responsibilities

Glioblastoma (GBM) remains the most malignant primary brain tumor. In spite of intensive treatment, current approaches are insufficiently effective to achieve major clinical benefits. GBM typically exhibits complex genetic aberrations which lead to extensive inter- and intratumoral heterogeneity. The presence of exceptional responders across many failed clinical trials suggests that GBM consists of dozens of small subgroups that likely all require a different therapeutic approach. Because this functional heterogeneity remains largely unexplored, this project aims at mapping single-cell drug responses across GBM tumor types. To achieve this, in this project, we will compare control- and drug-treated tumor samples using an ex vivo multi-omics approach combining transcriptomic and protein-based single cell measurements. As such, we will not only be able to define responsive and resistant tumor cell (sub)populations, it will also allow us to identify potential biomarkers for each included therapy. Appropriate experimental conditions and biomarkers will first be identified using a heterogeneous library of patient-derived GBM cell lines. Next, we will use mouse models of GBM to correlate the ex vivo and in vivo response capabilities at single cell level, to eventually analyse these features in freshly resected clinical tumor samples. Finally, we aim to further validate our findings using spatially resolved technologies (spatial multiplexed IHC or transcriptomics). This project will as such describe the landscape of drug responsiveness across GBM at unseen resolution, and provide a fundamental step towards more tailored therapies.

Profile

We are looking for a motivated and enthusiastic postdoctoral researcher with a strong interest in bioinformatics to strengthen our bio-informatics team of postdoctoral and PhD researchers. We look for someone who wants to use his project to grow his/her skills in single-cell data analysis and apply it to develop the clinical tools of the future. You will have the opportunity to work in a young, dynamic and interdisciplinary team that brings together bio-informaticians, clinicians, pathologists and molecular biologists.

Offer

We offer a full time 2-year postdoc position within our research team. The ability to apply for additional fellopwship is an additional plus (e.g. at www.FWO.be). During this time, you will also receive the chance to strategically shape the future of this challenging project.

Interested?

For more information please contact Prof. dr. Frederik De Smet, tel.: +32 16 37 25 75, mail: [email protected].

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