Don Fox, Ph.D.

Research

Our laboratory studies a poorly understood yet common cellular property- whole genome duplication or polyploidy. We study polyploid cells that contribute to normal organ formation in fruit flies, but closely resemble human cancer cells in that they produce cells with aberrant chromosome number (aneuploidy). Given the predictability of our developmental model and the ease of genetic perturbation in flies, we are currently uncovering mechanisms by which polyploidy enables such “genome instability.” A second focus of the lab is to understand how polyploidy contributes to tissue repair. We find that cell loss due to organ injury in the fly hindgut (colon) prompts tissue repair, but not through cell replacement. Rather, cells that replace lost tissue mass grow bigger- by becoming polyploid. We are now uncovering cues that prompt this alternative ploidy-driven mode of tissue repair, a mechanism that likely operates in our own heart and liver after injury. Our goal is to understand how organ aging decreases organ regeneration cues in favor of ploidy increase. While we are primarily working with flies, we have also initiated collaborative work in mammalian systems to identify evolutionarily conserved properties of polyploidy. Taken together, our work aims to elucidate roles for ploidy increase in physiology and disease.