From an interest in studying cellular DNA repair and recombination pathways, we recognized the utility of DNA triple helix formation as a mechanism for the site-specific introduction of DNA damage in mammalian cells.
We hypothesized that that acquired genetic instability in cancer cells may arise from the dysregulation of critical DNA repair pathways due to cell stresses within the tumor microenvironment such as hypoxia.
Cisplatin is one of the most widely used cancer chemotherapy agents, but its mechanism of action is not fully understood.
We are carrying out mutagenesis studies using a lambda phage vector construct as a chromosomal shuttle vector in transgenic mice and mouse cells.
There has been a surge of interest in DNA repair pathways as potential targets for cancer therapy strategies, not only to potentiate existing cancer therapies such as radiation and DNA damaging chemotherapy but also to take advantage of the frequent DNA repair abnormalities in human cancer cells to achieve synthetic lethality and consequent therapeutic gain.