Elevated oxidative stress and DNA replication stress are common in cancers. On one hand, these intrinsic stresses in cancer cells promote tumor initiation and progression. On the other hand, these stresses render cancer cells sensitive to radio and chemotherapies. Lan laboratory is especially interested in understanding how cancer cells respond to oxidative and replication stresses through DNA repair pathways and developing new strategies to target these pathways in cancer therapy. We have established an advanced laser micro-irradiation system to induce localized DNA damage in a single nucleus and investigated how DNA damage is repaired in live cells, also developed the first molecular assay to study the oxidative damage response at specific chromosomal loci. We have discovered and delineated a novel DNA repair pathway—RNA-mediated repair—that protects the transcribed regions of the genome, which is a new paradigm in the DNA repair field. The RNA-mediated repair has led to discoveries of new therapeutic targets and biomarkers in ovarian and breast cancers.
