Defects in the cellular DNA repair machinery can promote cancer formation and cause cancer cells to rely on back-up DNA repair processes. These cancer cells are particularly vulnerable to drugs called PARP inhibitors, which target a DNA repair process known as homologous recombination. Dr. Chan hypothesizes that a similar treatment strategy can be used for cancers with deficiencies in DNA mismatch repair, which causes microsatellite—short, repeated sequences of DNA—instability (MSI). Microsatellite instability is found most often in certain colon, stomach, uterine and ovarian cancers. Using CRISPR screening technology, Dr. Chan discovered that cancer cells with faulty mismatch repair become dependent on a gene called WRN to survive. He is characterizing this vulnerability for MSI cancers with the goal of finding new drugs that inhibit this pathway.