David Shechter, Ph.D.

Protein modification by methylation, the addition of a small chemical flag that regulates that protein's function, is frequently disrupted in lung cancer. Our proposal aims to understand why a class of enzymes that adds a methyl group to protein building blocks called arginine is disrupted in lung cancer cells and importantly how drugging these enzymes could be a novel chemotherapy. We will test, in lung cancer cells, specific drugs against these enzymes, one of which is currently in phase I trials, in combination with a range of other drugs to understand how they could work in combination. We will also probe specific and important molecular events that are regulated by these enzymes, in lung cancer cells. The information we develop from this study will potentially lead to improved chemotherapeutic approaches in lung and other human cancers.

Update: During the initial funding, we started multiple complementary studies in pursuit of our aims and have already made substantial progress. In lung adenocarcinoma cells we have employed drugs against protein arginine methyltransferase enzymes to understand the cellular and molecular functions promoted by these enzymes. We have learned important insights that will lead to improved diagnostics and more targeted chemotherapeutic approaches. We have determined molecular mechanisms of how arginine methyltransferases change the cell to promote altered cancer growth and how drugging these enzymes can rescue them from uncontrolled growth and metastasis. In this coming year, we will submit multiple papers to internationally regarded, high-profile journals reporting on this work.