The nuclear pore complex (NPC) has historically been regarded as a passive conduit for macromolecular trafficking, yet recent insights implicate specific nucleoporin subunits as dynamic regulators of chromatin architecture, signal transduction, and oncogenesis. My research interrogates the role of nucleoporin dysregulation in the molecular pathophysiology of Diffuse Intrinsic Pontine Glioma (DIPG) – a universally fatal, H3K27M-driven paediatric glioma characterised by epigenetic derangement and therapeutic intractability. I aim to delineate how aberrant nuclear-cytoplasmic transport, mediated through altered NPC composition or function, contributes to transcriptional misregulation, impaired DNA damage response, and cellular plasticity in DIPG. Through integration of CRISPR-based functional genomics, proteomics, and single-cell spatial transcriptomics, this project seeks to identify nucleoporin-dependent oncogenic dependencies amenable to targeted intervention. The broader objective is to establish a framework for nucleocytoplasmic transport as a clinically actionable axis in paediatric neuro-oncology, with translational implications for biomarker development and next-generation therapeutics.
Nucleoporin Dysfunction as a Molecular Target in Diffuse Intrinsic Pontine Glioma (DIPG)
