Our Research

Our laboratory is dedicated to advancing the understanding and treatment of pediatric low-grade gliomas (pLGGs), the most common brain tumors in children. While overall survival is high, many patients suffer from long-term morbidity due to tumor progression and treatment-related toxicities. Our multidisciplinary strategy integrates state-of-the-art models, tumor microenvironment (TME) analysis, and molecular biology to address critical gaps in pLGG biology and therapeutic development.

Understanding and Targeting pLGG Biology

Given the central role of MAPK pathway activation in pLGG, we continue to investigate its contribution to tumor growth, maintenance, and resistance to therapy. However, we also recognize that MAPK activation alone does not fully explain the clinical behavior of these tumors. Therefore, we are expanding our focus to identify additional signaling networks and regulatory mechanisms that may drive tumor progression or relapse. Our goal is to uncover actionable targets beyond MAPK, paving the way for combination therapies that are more effective and durable.

Model Development: Bridging Biological Complexity and Clinical Relevance

We have established a suite of experimental models to reflect the cellular and molecular diversity of pLGGs. This includes the generation of patient-derived cell lines engineered with an inducible SV40 large T antigen to bypass oncogene-induced senescence and enable sustained in vitro culture. Building on this, we are developing 3D co-culture systems – termed artificial tumoroids – that combine these tumor cell lines with iPSC-derived TME components such as microglia and neurons. We also generate patient-derived tumoroids to maintain native tumor architecture and heterogeneity. These models provide a translational platform to interrogate tumor biology and test therapeutic responses in a physiologically relevant context.

Decoding Tumor-TME Crosstalk

Our research seeks to unravel the complex interactions between tumor cells and their microenvironment, with a particular focus on the influence of the MAPK pathway and immune modulation. We aim to dissect how TME components, including microglia and neurons, contribute to tumor progression and therapeutic resistance, especially under MAPK inhibitor (MAPKi) treatment. Through integrated transcriptomic and functional analyses, we are identifying molecular mediators of tumor–TME communication that could serve as novel therapeutic targets or biomarkers of treatment response.

Through this triad of pathway dissection, model innovation and TME decoding, we aim to transform pLGG management. Our research directly informs clinical strategies and paves the way for more precise and less toxic therapies for children with pLGG.