CRIG 'young investigator proof-of-concept projects’: laureates 13th call

In collaboration with vzw Kinderkankerfonds, CRIG provides research grants for young (postdoctoral) cancer researchers at CRIG to initiate potentially high-risk and innovative cancer research projects. In this 13th call, following postdocs were awarded, and will start their project in April.

• Dr. Sarah Bonte – ‘Towards an automated detection tool for measurable residual disease in acute myeloid leukemia' (promotors of the grant: Prof. Yvan Saeys & Prof. Tessa Kerre) - The presence of measurable residual disease (MRD) after initial treatment is an important negative prognostic factor for the risk of relapse in several hematological malignancies and is therefore often used to guide therapeutic decision-making. In theory, flow cytometry is an ideal technique to detect MRD, but in practice this remains challenging as manual analysis is difficult, time-consuming, operator-dependent and difficult to standardize across centers. Therefore, the team of Prof. Saeys wants to develop a computational method for automated detection of MRD in flow cytometry data of patients with hematological malignancies. As a proof-of-concept, Sarah will acquire flow cytometry data, stained with a 24-color spectral flow cytometry panel, from patients with acute myeloid leukemia and healthy controls to develop a tool that is able to automatically identify aberrant cells in the patient samples, based on different unsupervised clustering approaches.
   
• Dr. Mohammad Rahimi Gorji – ‘Developing a coupled in silico-experimental approach to optimize intraperitoneal aerosolized drug delivery using a realistic patient-specific abdominal model’ (promotors of the grant: Prof. Wim Ceelen & Prof. Charlotte Debbaut) - Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel treatment method for peritoneal metastases. During PIPAC, a CO2 pneumoperitoneum is established (12 mmHg) to insufflate the peritoneal cavity, followed by nebulization of chemotherapy using a specific atomizer and high-pressure injector. The research question the teams of Prof. Ceelen & Prof. Debbaut focus on is “How can we optimize the current PIPAC technique to improve treatment efficacy for patients with peritoneal metastases?”. To answer this question, a combined computational and experimental approach merging the principles of computational fluid dynamic (CFD) simulation, in vitro/ex vivo experiments, 3D printing technology, and high-speed imaging is used. To optimize the technique, it is important to be able to model the effect of several parameters on aerosol droplet distribution in the peritoneal cavity. To do so, the group of Prof. Ceelen & Prof. Debbaut initially used a simple plexiglass box model representing the peritoneal cavity. For the next step, they want to investigate the PIPAC treatment using a 3D reconstructed human peritoneal cavity based on a CT-scan dataset. In this project, Mohammad will design, develop and produce a physical model of a novel, realistic 3D peritoneal cavity and accompanying CFD methods based on the real human anatomy, with the final aim of optimizing PIPAC treatment parameters.
   
• Dr. Joachim Siaw - 'A spatial transcriptomic approach to determine the tumour micro-environment response to pharmacological inhibition of RUVBL1/2 as promising novel therapeutic targets for high-risk neuroblastoma’ (promotors of the grant: Prof. Jimmy Van den Eynden & Prof. Kaat Durinck) - High-risk neuroblastoma (NB) accounts for about 50% of all NB cases and has a relapse rate of more than 50% despite intensive therapies. Moreover, life-threatening toxicities occur in many high-risk patients during and after treatment with cytotoxic chemotherapy and radiotherapy. Hence, less toxic and more effective drugs are urgently needed to treat high-risk NB. MYCN amplification, one of the strongest prognostic biomarkers, together with high MYC expression are believed to drive a substantial proportion of high-risk NB. The group of Prof. Van den Eynden has identified RuvB-like 1 and RuvB-like 2 (RUVBL1/2) as key novel interactors within the MYCN/MYC regulatory network. In this project, Joachim will investigate the therapeutic efficacy of a RUVBL1/2 inhibitor in genetically engineered mouse models for neuroblastoma and will try to uncover the spatial signaling dynamics in the tumor microenvironment upon drug exposure.
   
• Dr. Jonas Steenbrugge – ‘Proof-of-concept on lipocalin 2 as novel immunotherapeutic and lymphangiogenic target in triple-negative breast cancer’ (promotors of the grant: Prof. Evelyne Meyer & Prof. Niek Sanders) – Triple-negative breast cancer (TNBC) differs from other types of breast cancer as it tends to grow and spread faster, has fewer treatment options and has a significantly worse prognosis. Therefore, there is a medical need for new and optimized therapies for patients confronted with the disease. Lipocalin 2 (LCN2) is an iron-chelating glycoprotein secreted by tumor-associated macrophages (TAMs) that has a potent pro-tumorigenic role in solid tumors through iron delivery in the tumor microenvironment (TME) for tumor growth and secretion of chemoattractants for additional TAMs and immunosuppressive neutrophil precursors. Based on the currently available preclinical and clinical data, the group of Prof. Meyer hypothesizes that LCN2 might hamper immunotherapy in TNBC patients through immunosuppression and may have a role in lymphatic metastasis by modulating TAMs and their integration into lymphatic vessels. In this project, Jonas will investigate both hypotheses by blocking LCN2 with an antibody in a 4T1-based intraductal model for TNBC and identifying whether it overcomes resistance for anti-programmed death (PD)-1 immune checkpoint blockade as well as reduces TAM-mediated lymphatic remodeling. Furthermore, the association between LCN2 levels and immunotherapeutic responses at the clinical level will also be studied through prospectively collected blood plasma samples from metastatic TNBC patients receiving immunotherapy.