“Our lab is all about big data.”

A major cause of cancer treatment failure is the development of therapy resistance in tumors, which evolve by accumulating tumor-promoting mutations and modified chromosome structures in a subset of their cells. Our lab addresses this through computational and statistical analysis of large-scale biomolecular data — centered on extrachromosomal DNA (ecDNA), a circular, chromosome-free form of oncogene amplification we and our collaborators have shown to be far more common, and far more consequential, than once thought. Our work spans long- and short-read sequencing, single-cell and spatial multiomics, FISH validation, and structural variant analysis, in close collaboration with colleagues across cancer biology, epigenetics, structural biology, bioimaging, and tumor microenvironment research.

ecDNA: Mechanics, Functions & Therapeutic Implications

Our most comprehensive synthesis to date brings together what we and the field now understand about the mechanical properties, biological functions, and emerging therapeutic angles of extrachromosomal DNA (ecDNA) in cancer (Kim et al., Signal Transduction and Targeted Therapy, 2026) — work that builds directly on our pan-cancer survey finding circular ecDNA in over 25 of 29 cancer types, far more common than the <1% once assumed, and linked to significantly shorter patient survival (Kim et al., Nature Genetics, 2024). EcDNAs were first recognized through pioneering cytopathology studies by Arthur Spriggs over 50 years ago, yet how they drive tumorigenesis is still being uncovered. We study this with a broad toolkit: long- and short-read whole-genome and exome sequencing, single-cell multiomics, FISH-based validation, and structural variant analysis, backed by AmpliconSuite, an end-to-end computational workflow we co-developed for detecting focal amplifications in cancer genomes — including our latest work tracking how ecDNA is inherited and restructured at single-cell resolution as tumors evolve (Yeo et al., Experimental & Molecular Medicine, 2026).

Tumor Evolution & Glioma Origin

Our computational and experimental analysis of glioblastoma patients and their derived model systems identified non-chromosomal ecDNA amplification as a driver of intratumor heterogeneity, providing direct evidence that extrachromosomal oncogene amplification accelerates tumor evolution. Using single-cell multimodal profiling — pairing DNA methylomes with transcriptomes — we've also identified epigenetic regulators of cellular plasticity under environmental stress (Johnson et al., Nature Genetics, 2021). More recently, in collaboration with the Glioma Longitudinal AnalySiS (GLASS) consortium we co-founded (Varn et al., Cell, 2022), we helped trace IDH-mutant glioma back to the glial progenitor cells that first carry the driver mutation — clarifying how these tumors begin, not just how they progress (Park et al., Science, 2026).

ecDNA Across Cancer Types & New Research Platforms

ecDNA's reach extends well beyond glioma. We've mapped its distinct molecular signatures and prognostic weight in gastric cancer (Kang et al., Cancer Letters, 2026), used spatial and genomic profiling to trace how breast cancer subtypes diverge after neoadjuvant chemotherapy (Seo et al., Cell Reports Medicine, 2025), and shown that ecDNA also drives the earliest steps of Barrett's esophagus turning cancerous (Luebeck et al., Nature, 2023). To study these effects more faithfully than standard 2D culture allows, we're also building tailorable 3D collagen hydrogel platforms that better preserve ecDNA structures and tumor microenvironment biology for long-term study (Jo & Shon et al., Theranostics, 2026).