16 | LEHIGH ALUMNI BULLETIN Every day, the DNA in our cells that keep us alive can suffer damage from air pollution, cigarette smoke, background radiation and even routine cell division. Fortunately, our cells are equipped with sophisticated repair machinery, a suite of enzymes that detect and fix DNA damage before it leads to mutations or cell death. But this protective system can go awry. Some of the most important cancer therapies work by damaging DNA. Cancer cells will therefore hijack DNA repair machinery to fix the therapy-induced damage and resist frontline treatments. Developing innovative tools to understand exactly how cancer cells exploit DNA repair and how to turn that knowledge into better treatments is the focus of work underway by Daniel Laverty, biochemist and assistant professor of chemistry in the College of Arts and Sciences. Laverty’s research creates functional assays, molecular tools that measure specific DNA repair pathways in living cells. These assays address a fundamental challenge in cancer research. DNA can be damaged in myriad ways, making it difficult to pinpoint which repair pathways are most important in a tumor. His solution is elegant. His lab creates circular DNA molecules called plasmids that encode for fluorescent or luminescent proteins. Then they introduce a specific type of DNA damage, and transfer the plasmid into human cells, where they exist separately from the cell’s chromosomes. If the DNA damage gets repaired, the cell will emit fluorescence or luminescence, providing a readout of how efficiently the cells repaired the DNA damage. Laverty’s research program has two complementary goals. First, his team investigates the fundamental molecular mechanisms of DNA repair, focusing on how cells handle double-strand breaks and a process called translesion synthesis, which allows cells to tolerate unrepaired damage and restart DNA replication. The second thrust has direct clinical implications, understanding how cancer cells develop resistance to treatment. Many cancers initially respond to chemotherapy or radiation but eventually become resistant. The ultimate goal is more precise cancer therapy. Current treatments like chemotherapy work by overwhelming cells with DNA damage—they kill cancer cells effectively but also harm healthy, rapidly dividing cells throughout the body, causing severe side effects. Laverty envisions a different approach–combining lower doses of conventional therapy with targeted inhibitors of specific DNA repair pathways. By understanding exactly how cancer cells resist treatment, and designing functional assays that can detect this resistance in real time, his work could help move cancer therapy to a precision tool.—Rob Nichols Decoding Cancer’s Resistance to Treatment | LEHIGH ALUMNI BULLETIN
RkJQdWJsaXNoZXIy MTA0OTQ5OA==