Research in the Shor Lab
Dr. Shor’s research program focuses predominantly on the mechanisms driving the emergence of drug resistance in C. glabrata, ranging from the mechanisms underpinning drug tolerance to those regulating genome instability and formation of genetic mutations conferring stable drug resistance. Some past and ongoing projects include:
- Developing a fluorescence-based mutation rate reporter assay in C. glabrata, which can be used in both drug-sensitive and drug-resistant clinical strains.
- Showing that the DNA damage checkpoint of C. glabrata is strongly attenuated relative to that of its close relative S. cerevisiae, which has implications for how this organism responds to DNA damage in vivo (e.g., in macrophages) and the development of genetic instability, including drug-resistant mutations.
- Identifying the host niches where genotypically sensitive but phenotypically resistant (a.k.a., drug-tolerant) C. glabrata cells survive despite treatment with cidal antifungal agents (such as echinocandins), thus forming a reservoir in which drug-resistant mutants can form. We are also focusing on elucidating the characteristics of such surviving persister cells, defining their evolutionary/mutational routes to resistance, and understanding the processes regulating genome stability and mutagenesis in these cells.