Alicia Darnell, PhD

Cancer cells are always growing, and they need nutrients to keep up this fast growth. An exciting idea is that we might be able to starve cancer cells without harming healthy cells by getting rid of nutrients that cancer cells need. A drug being developed right now called ADI-PEG20 destroys a nutrient called arginine, which is an amino acid that is used to make protein and is particularly important for cancer cells. My lab studies what happens when cancer cells don’t have enough arginine. We want to understand how ADI-PEG20 works, how to improve it, and which cancers to treat with it. We have found that restricting arginine disrupts ribosomes, the machines that build new protein, causing them to get stuck and abandon their jobs early. We want to study three things to figure out how this impacts ADI-PEG20 treatment. First, why is protein production in cancer cells so sensitive to arginine levels? Next, what machinery in the cell is responsible for causing “starved” ribosomes to press the eject button in the middle of doing their jobs? Finally, what effect does this have on a cancer cell? This work will help us understand how a nutrient like arginine can directly control very important processes in the cell like protein production. It will also reveal how we can take advantage of cancer’s dependence on arginine to shrink tumors.