CRIG 'young investigator proof-of-concept projects’: laureates 14th call

In collaboration with vzw Kinderkankerfonds, CRIG provides research grants for young (postdoctoral and/or senior doctoral) cancer researchers at CRIG to initiate potentially high-risk and innovative cancer research projects. In this 14th call, following postdocs were awarded, and have started their project in this month.

• Dr. Jill Deleu – ‘The exploration of cell-free mRNA to monitor therapy response in a neuroblastoma xenograft model’ (promotors of the grant: Prof. Jo Vandesompele, Prof. Bram De Wilde & Prof. Tom Van Maerken) - Unfortunately, the prognosis for most high-risk neuroblastoma patients remains poor, and the prevalence of chronic disease due to treatment related toxicities high. Targeted cancer therapeutics might lower this toxicity, but require insights into the mechanisms of drug efficacy and resistance. Understanding the differential (molecular) response of neuroblastoma patients to therapies is therefore a pressing clinical need. Unfortunately, longitudinal sampling of tumor tissue to assess treatment response is not feasible due to invasiveness, costs, and often limited accessibility. Furthermore, it often does not reflect the tumor heterogeneity, as only a small part of the tumor is sampled. In her project, Jill will investigate whether cell-free RNA, especially mRNA can be exploited to monitor on target activity of an anti-cancer drug by using blood from neuroblastoma xenograft models.
   
• Dr. Lisa Depestel – ‘Disrupting RRM2-PHF6 interaction to target replication stress resistance in neuroblastoma’ (promotors of the grant: Prof. Frank Speleman & Prof. Kaat Durinck) - Neuroblastoma is a pediatric tumor of the sympathetic nervous system with poor survival for high-risk cases. Many cancer cells, including neuroblastomas, show an increased dependency on replicative stress response pathways to keep up with their high and error-prone proliferation activity. Recently, the group of Prof. Speleman and Prof. Durinck have identified the interaction between RRM2 and PHF6 as important in this neuroblastoma cell replication stress resistance. Therefore, in her project, Lisa will try to identify compounds that potentially can disrupt this PHF6-RRM2 interaction, and might therefore hold therapeutic potential for the treatment of high-risk neuroblastoma patients.
   
• Dr. Cláudio Pinheiro – ‘A fine-grained view on the biomolecular corona of extracellular vesicles to steer therapeutic applications’ (promotor of the grant: Prof. An Hendrix) - Extracellular vesicles (EVs) are complex nanoparticles required for the intercellular transfer of diverse biological cargoes. Recently, a tremendous interest in exploiting EVs as advanced nano delivery systems (NDS) for the treatment of a range of challenging pathologies, including cancer, has arisen. Similar to other NDS, EVs are known to acquire a biomolecular corona upon administration which impacts their bioactivity and might serve as potential disease biomarkers. However, there is a current lack of knowledge on the composition of this corona and its impact on EV uptake and (sub)cellular interaction, which hampers the clinical translation of EV-based therapeutics. In his project, Cláudio will use cutting-edge technologies to allow for in-depth mapping and interpretation of the EV-associated protein corona. Hopefully, his work will serve as a foundation for the use of EVs as NDS for the treatment of several diseases.
   
• Dr. Niki Rashidian – ‘Towards Dynamic Image-Guided Hepatectomy using Computer Vision for 3-D Scene Rendering’ (promotor of the grant: Prof. Frederik Berrevoet) - Advances in computer technology and data science, particularly with 3-D models based on preoperative imaging, have improved precision in liver surgery. These 3-D models can be overlaid via Augmented Reality during surgery to provide intraoperative guidance. However, an important limitation of this approach is the static nature of these image-based 3-D models, as various factors can introduce changes within the abdominal cavity during minimally invasive liver surgery. Ideally, we need a flexible modeling process with dynamic registration, and capable of providing real-time feedback to the surgeon with minimal impact on surgical workflow. The overall objective of Niki’s project is to investigate the feasibility of integrating a dynamic 3-D reconstruction system based on Neural Radiance Fields with existing static image-based 3-D models for image-guided cancer surgery.
   
• Dr. Martijn Schuijs – ‘Defining novel alveolar macrophage gene-targets to prevent pulmonary metastasis’ (promotor of the grant: Prof. Geert Berx & head of the research lab: Prof. Bart Lambrecht) - Metastatic disease accounts for over 90% of cancer-related deaths, with the lung as a common site for metastases. Within the steady-state lung, tissue-resident Alveolar Macrophages (AMs) stabily occupy the alveolar niche and self-maintain throughout life via local proliferation. However, there is very limited insight in how these cells affect the metastatic niche. Recently, the group of Martijn developed a SPecific Alveolar Macrophage deleter (SPAM) mouse, allowing for highly specific and inducible AM depletion, and showed the importance of these lung resident macrophages during metastatic disease. In his project, Martijn will further investigate the link between AMs and pulmonary metastases, by creating a pipeline to screen and validate trAM-specific genes and pathways influencing pulmonary metastasis, using CRISPR-Cas9.
• Dr. Sandra Van Lint – ‘Reprogramming monocyte transcriptional circuits for fast and autonomous generation of dendritic cells for cancer immunotherapy’ (promotor of the grant: Prof. Karim Vermaelen) - Dendritic cells are uniquely endowed with the power to elicit de novo T-cell responses against cancer, spurring numerous attempts to generate these cells ex vivo for reinjection into cancer patients (a form of cell-based vaccine). In most cases therapeutic DCs are produced by exposing patient-autologous monocytes cultures sequentially to several combinations of recombinant factors to achieve maturation, followed by an antigen loading step (in our case by electroporation of antigen-encoding mRNA). Although this method allows to generate large batches of fully active cells for repeated injection into the cancer patient, the complexity and cost of the process hampers large-scale implementation. In this project, Sandra wants to develop a simple and elegant way to generate autologous dendritic cells for cancer immunotherapy by replacing the consecutive addition steps of expensive cytokines to the cell culture by an ingenious and highly simplified process that could make a huge difference in terms of production time and costs.