Research

Poly (ADP-ribose) polymerase inhibitors have become a paradigm for targeted cancer therapy in treating ovarian & breast cancer patients carrying BRCA1/2 mutations. Despite the success of PARP inhibitors in cancer treatment, various resistance mechanisms develop to limit their clinical efficacy. Our lab focused on studying the emerging roles of RNA-binding proteins in DNA repair and sensitivity/resistance to PARP inhibitor.

Poly (ADP-ribose) polymerase-1 (PARP-1) is activated by damaged DNA and synthesizes poly(ADP-ribose), which acts as a scaffold to recruit DNA repair proteins to the site of damage. In addition to the classical role of poly (ADP-ribose) in DNA repair, we are also exploring its involvement in modulating DNA/RNA hybrid (R-loop) formation, as well as the previously unexplored effects of poly (ADP-ribose) on the regulation of metabolic enzymes.

5-FU’s utility in cancer treatment has long been attributed to inducing dNTP imbalance and DNA damage in cancer cells. Recently, we demonstrate that 5-FU’s efficacy results instead from RNA damage during ribosome biogenesis. We are currently investigating the molecular quality control mechanism by which 5-FU-containing RNAs are sensed and elucidating the signaling pathways linking damaged RNA to cell death.