Research

Chromosomal Instability in Cancer

A key feature of tumor progression is increased chromosome instability - often manifesting as copy-number alterations and extrachromosomal DNA (ecDNA). Genomic instability is strongly associated with drug resistance and progression to late-stage, metastatic disease. Thus, one of our central goals is to understand the mechanisms by which genomes become increasingly unstable and how copy-number changes (especially ecDNA) affect the molecular state of cells, tumors, and patients. Our hope is to find targets that are robust to, or suppress entirely, genomic instability. 

We approach these studies by combining cutting-edge experimental approaches (e.g., those allow us to “write” ecDNA in cells) with innovative computational tools for new genomic and imaging technologies, including single-cell, spatial, and long-read genomics approaches.

Key Publications

  1. Hung KL*, Jones MG*, Wong ITL*, Curtis EJ*, et al. Coordinated inheritance of extrachromosomal DNA species in human cancer cells. Nature. 2024

  2. Zhu K*, Jones MG*, Luebeck J, et al. CoRAL accurately resolves extrachromosomal DNA genome structures with long-read sequencing. Genome Research. 2024.

  3. Kraft K*, Murphy SE*, Jones MG*, et al. Enhancer activation from transposable elements in extrachromosomal DNA. BioRxiv. 2024

Tracing the evolution of biological systems

Evolutionary principles underpin biological processes across several scales - from species evolution to cellular lineages. This is especially true in cancer, where cancer cells diversify rapidly and co-opt the principles of evolution to grow, colonize distant tissues, and evade therapies. Our goal is to dissect the evolutionary processes enabling cancer cells to adapt and transition to malignant states, and in doing so improve our ability to detect cancer and monitor its progression.

We aim to study tumor evolution in experimental systems and patients alike, where we apply several approaches including lineage-tracing technologies (e.g., CRISPR/Cas9-based evolvable recorders), phylogenetic inference, and evolutionary modeling.

Spatial biology of cancer

Just like any tissue, the organization of a tumor is critical to its function. Some of the earliest observations by cancer biologists noted that aggressive tumors were characterized by tissue disorganization and dysfunction; more recently, studies have begun to finely characterize the changes following tumor progression using technologies that enable high-resolution spatial molecular phenotyping. We aim to utilize these emerging tools to further understand how the spatial organization of tumors changes over time, and how this spatial organization can be modulated.

Recently, we pioneered the use of CRISPR/Cas9-based lineage-tracing to study the spatiotemporal evolution of tumors. We continue to combine these approaches with new computational tools and experimental systems to study how tumors are formed over time, and how these processes can be therapeutically targeted.

Key Publications

  1. Jones MG*, Sun D*, et al. Spatiotemporal lineage tracing reveals the dynamic spatial architecture of tumor growth and metastasis. BioRxiv. 2024.

  2. Koblan LW*, Yost KE*, Zheng P*, Colgan WN*, Jones MG, et al. High-resolution spatial mapping of cell state and lineage dynamics in vivo with PEtracer. BioRxiv. 2025.

  3. Huang YH, Belk JA, Zhang R, Weiser NE, Chiang Z, Jones MG, et al. Unified molecular approach for spatial epigenome, transcriptome, and cell lineages. PNAS. 2025