SPATIAL-RESIST: Spatial Functional Genomics of Therapy Resistance in Brain and Spine Tumors

We are developing a collaborative project to identify spatially organised tumour cell states and functional dependencies driving therapy resistance and recurrence in high-grade glioma and/or spinal metastatic tumours. We seek partners with expertise in spatial transcriptomics, CRISPR screening and in vivo models.

Project concept: Both high-grade gliomas and spinal metastases are highly heterogeneous, therapy-resistant and associated with poor outcomes. We hypothesise that recurrence is driven not only by genomic alterations, but by spatially organised cellular states that survive therapy, adapt to microenvironments and acquire specific functional dependencies. In glioma, this reflects evolution under therapy; in spinal metastases, it includes adaptation to the bone–marrow niche.

Paired primary and recurrent samples will be analysed using sn/scRNA-seq and/or spatial transcriptomics, with optional epigenomic integration. We will identify programmes linked to stemness, EMT, invasion, hypoxia, DNA repair, metabolic adaptation, immune evasion and bone-niche adaptation.

Our foundation: We collaborate with neurosurgery, neuro-oncology and spine oncology teams, ensuring access to clinically annotated material and longitudinal follow-up. Our clinical research includes biostatistical support in a randomised study of FET-PET/MRI in glioblastoma surgery and radiotherapy, and prospective studies in spinal metastases. We are also part of the OncoSpine Unit.

Available capabilities: We provide:

• processing of glioma and spinal metastasis samples;

• bulk RNA-seq and sn/scRNA-seq;

• nuclei isolation and single-cell workflows;

• 2D, 3D and organoid models;

• functional assays and molecular biology;

• CAGE-seq;

• differential expression, GSEA, WGCNA;

• pathway and network analysis;

• clustering, trajectory and pseudotime analysis;

• tumour heterogeneity and cell–cell interaction analysis;

• multi-omics integration;

• survival and predictive modelling;

• AI/XAI and biostatistics.

Spatial & functional strategy: Spatial transcriptomics will map tumour states in invasive, hypoxic and therapy-resistant regions and, in spinal metastases, within the bone–marrow niche. Integration with single-cell data will define regulatory programmes and candidate vulnerabilities. A CRISPR partner will test dependencies under radiotherapy, chemotherapy, hypoxia, metabolic stress and bone-microenvironment conditions. Top targets will be validated in organoid and 2D/3D models, and then in orthotopic glioma or bone-metastasis in vivo systems.

Partnership sought: We seek partners with expertise in

• CRISPR/CRISPRi functional screening;

• spatial transcriptomics and bioinformatics;

• spatial multi-omics/epigenomics;

• glioma and/or bone-metastasis in vivo models;

• drug/combination screening;

• longitudinal clinical cohorts;

• target validation and drug development.

Expected outcome: We aim to establish a spatially resolved functional precision-oncology framework explaining how resistant tumour states emerge, where they localise, how they adapt to brain and/or bone environments, and which dependencies can be therapeutically targeted. This dual-disease approach enables discovery of both shared resistance mechanisms and niche-specific adaptation programmes, particularly in spinal metastases, but it may also be treated as separate projects.