Our genomes are far from static. Sequencing studies in humans and model organisms reveal striking differences in genome structure and composition—even among individuals of the same species. These variations often arise as adaptive responses: cells adjust to shifts in their environment or to disruptions within their own genetic machinery. Remarkably, such compensatory changes can mean the difference between death and survival, allowing cells carrying potentially lethal mutations to function as if nothing were wrong.
I study the molecular mechanisms that drive these processes. By uncovering how the many “microscopic engines” inside cells interact, we aim to understand the principles of genome stability, adaptation, and resilience. This knowledge not only deepens our view of evolution but may also point the way toward new strategies for preventing or overcoming genetic disease.
Latest works
Mutagenic mechanisms of cancer-associated DNA polymerase epsilon alleles
Mareike Herzog, et al.
Nucleic Acids Research, March 2021
A single amino acid residue change in the exonuclease domain of human DNA polymerase epsilon, P286R, is associated with the development of colorectal cancers, and has been shown to impart a mutagenic phenotype. … >continue
Trajectory of mutational signatures in yeast mutators
Sophie Loeillet, et al.
Proceedings of the Nat’l Academy of Sciences USA September 2020
The acquisition of mutations plays critical roles in adaptation, evolution, senescence, and tumorigenesis. Massive genome sequencing has allowed extraction of specific features of many mutational landscapes but it remains difficult to retrospectively determine the mechanistic origin… >continue
Genome architecture and stability in the Saccharomyces cerevisiae knockout collection.
Fabio Puddu, et al.
Nature,573(416–420), September 2019
Despite major progress in defining the functional roles of genes, a complete understanding of their influences is far from being realized, even in relatively simple organisms… >continue