Research Themes

One of the major tools used in the Barnes Lab is the flourogen activating peptide (FAP) system. Developed by Marcel Bruchez, FAP binds photosensitizer dyes like malachite green, making them excitable by far-red light. We fused the FAP to histone H2B, so when cells are treated with dye and light, we can produce singlet oxygen throughout chromatin. This reacts rather specifically with guanine to produce the common oxidative lesion, 8-oxo-guanine (8oxoG). 

The lab is currently characterizing this new FAP system, and studying its effects on genome stability. Our early results show cancer and non-cancer cells stably maintain H2B-FAP to no ill effect, but when activated, display dose-dependent growth defects.

Due to the success of PARP inhibitors in homologous recombination deficient cancers, many groups are looking for new ways to improve the efficacy of other DNA damage response inhibitors. ATR inhibitors are gaining clinical attention since cancer cells are highly reliant on ATR signaling to maintain their hyper-proliferative lifestyle. The lab is currently studying how oxidative base damage at telomeres can sensitize cancer cells to ATR and downstream effector inhibition.