Research
How do living cells maintain their genome integrity?
Every time a cell divides, it must accurately and efficiently copy its genome while repairing damage stemming from intrinsic metabolic activity or environmental factors. Unrepaired damage and replication errors drive mutation accumulation, genome instability, and cell death. Our lab studies the mechanisms cells use to maintain their genomes under these pressures. Specifically, we are interested in how the replication machinery copies DNA faithfully, how conflicts between concurrent processes on the chromosome are resolved, and how damage is sensed and repaired. These processes are critical to human health because they underlie the evolution of drug resistance and cancer development.
We use a variety of model organisms, and take a multi-disciplinary approach that combines genetics, biochemistry, cell biology, proteomics, and genomics. By working across scales — from individual molecules to whole genomes — we aim to build a mechanistic picture of how cells maintain their essential functions.
Area 01 · Replication-transcription conflicts
How do DNA replication and transcription function concurrently?
DNA replication is an essential process for all living things. The fidelity and efficiency of DNA replication are essential for ensuring propagation of genetic information. Transcription of genomic DNA by RNA Polymerase is similarly essential and uses the same template at the same time as DNA replication, leading to inevitable replication-transcription conflicts. A long-term goal of the lab is to determine the mechanisms leading to transcription-dependent genomic instability, and the systems used by living cells to resolve conflicts between replication and transcription.
Area 02 · C. jejuni genome maintenance
How does Campylobacter jejuni maintain its genome?
Campylobacter jejuni is one of the most common causes of bacterial foodborne illness worldwide, and resistance to fluoroquinolones — a front-line treatment — is climbing. We study how C. jejuni copies and protects its genome, and how those core processes shape the way the bacterium survives antibiotics and evolves resistance. By connecting the mechanics of DNA replication fidelity to clinically important resistance phenotypes, we aim to understand not just how resistance arises, but how the pathogen's basic biology makes it possible.
Area 03 · Host-Pathogen Interactions
How do bacterial pathogens manipulate the host genome during infection?
Some bacterial pathogens reach directly into the host cell nucleus. They secrete effector proteins called nucleomodulins that enter the nucleus and manipulate the host's own machinery — remodeling chromatin, altering histone modifications, and rewiring transcription to reprogram host gene expression in the pathogen's favor. A growing number also target host DNA replication and repair. We study how these effectors work at the molecular level and what their activity reveals about the host processes they hijack, connecting bacterial infection strategy to the fundamental biology of the eukaryotic nucleus.