Research

Brain tumors evolve through changes in genotype, cell state, lineage composition, and interactions with the surrounding brain and immune microenvironment. These processes unfold during therapy and can produce clinically important resistance without a single dominant DNA mutation.

The Diaz Lab combines longitudinal clinical specimens, single-cell and spatial multiomics, genetic lineage tracing, machine learning, and experimental models to resolve these processes. Across adult and pediatric brain tumors and brain metastases, we seek to identify causal mechanisms, predictive biomarkers, and therapeutic combinations that can be advanced through clinical and industry partnerships.

Paired primary and recurrent glioblastomas connected across a therapy interval to genomic, single-cell, spatial, and proteomic profiling and integrated analysis.

Tumor Evolution Under Therapy

Longitudinal genomic, single-cell, spatial, and clinical studies reveal how glioma cell states and molecular programs change under therapy in glioblastoma and IDH-mutant glioma.

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A branching tumor-cell lineage tree connects static barcodes and mutable recorders to transcriptional state, chromatin state, genotype, spatial position, and treatment response, including uncertain ancestry branches.

Lineage Tracing and Predictive Computation

Experimental lineage recording and computational methods connect cellular ancestry with molecular phenotype, spatial context, and treatment response.

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Conceptual comparison of medulloblastoma developmental hierarchies and spatial cell states with adaptive mitochondrial and metabolic states in diffuse midline glioma after therapy.

Pediatric Brain Tumors

We study developmental and therapy-driven programs in medulloblastoma and diffuse midline glioma, including longitudinal SHH medulloblastoma evolution, developmental–cancer genetic convergence, and adaptive resistance to dordaviprone.

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Longitudinal schematic from a primary tumor through brain metastasis and later recurrence, integrating genomics, ecDNA, single-cell and spatial profiling, imaging, and treatment history.

Brain Metastasis

Longitudinal, multimodal studies examine brain-metastatic evolution and extrachromosomal DNA (ecDNA), supported by the BRIDGE, TRACE, and BMCA collaborative research infrastructure.

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Tumor–immune microenvironment showing immune-rich and immune-excluded regions, treatment-induced tumor-cell death and immune activation, and profiling workflows for studying response and resistance.

Tumor Immunity and Translational Therapeutics

Spatial and molecular studies connect tumor–immune interactions, immunotherapy, oncolytic virotherapy, and neoantigens to mechanisms of therapeutic response and resistance.

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