Research

The structure and consequences of complex cancer genomes.

Cancer genomes are often rearranged far beyond point mutations. Segments of DNA are amplified, broken and rejoined into complex structures, including extrachromosomal DNA (ecDNA), breakage-fusion-bridge cycles and other focal amplifications. These structures can carry dozens of copies of an oncogene, and they shape how a tumour grows, evolves and responds to treatment.

Sequencing breaks these structures into short fragments, so recovering them means rebuilding the genome's architecture from indirect evidence, usually by building and searching a breakpoint graph. I develop methods that do this with short-read, long-read and optical-mapping data, and that classify what they find.

With collaborators, I use these methods to ask what the structures do: when they arise, how they evolve, and how they change gene expression and therapy response. ecDNA has been a particular focus, because it is inherited unevenly at cell division and is linked to drug resistance and poor outcomes. The tools are now widely used to study ecDNA and focal amplification, including in pan-cancer analyses of TCGA, PCAWG and the 100,000 Genomes Project. See how they are used.

Selected work

See all 45 publications →

Collaborations

  • eDyNAmiC, Cancer Grand ChallengesComputational tooling for an international ecDNA team.
  • ARPA-H ADAPT program

Research computing

I run Genomequery, our group's research computing cluster, located in the data center of the UC San Diego Computer Science and Engineering building. It is a multi-node Linux cluster with 182 cores and 375 TB of storage. I oversee its system architecture, hardware and software upgrades, and the NIST SP 800-171 compliance process that lets the group analyse controlled-access genomic data.

In the media