Mapping the pathways to PARP inhibitor resistance by single cell sequencing

Initial characterization of the PARP treated cell population will involve mammalian cell culture and drug treatment assays. Flow cytometry will be used to characterize sub-populations in terms of cell cycle dynamics and long term survival.
Single cell genome re-sequencing will be applied to these heterogenous populations at various times during drug treatment to determine the extent to which PARP inhibition drives genome rearrangements. Combination studies will be performed with inhibitors of pol theta, an enzyme important for double strand break repair.