Michael Kharas, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Neuroblastoma is a childhood cancer that can be very hard to treat, especially when it comes back after therapy. Many tumors rely on a powerful cancer gene called MYCN, but we still do not fully understand how cancer cells keep MYCN active. Our research focuses on a group of proteins, called MSI1 and MSI2, that help cancer cells make the proteins they need to grow and survive. We have discovered that MSI1 and MSI2 act like a control switch for cancer cells. It helps turn on the production of important cancer-driving proteins, including MYCN. We also found that MSI2 is regulated by another process called arginine methylation, which changes how MSI2 works inside the cell. This gives us a new way to understand how cancer cells control growth at a deeper level. In this project, we will study how MSI proteins help neuroblastoma cells grow and change their identity. We will also test new treatment strategies that block MSI2 and the enzymes that control it. Our goal is to stop cancer cells from making the proteins they need to survive. This research may lead to new treatments that target cancer in a different way—by blocking how cancer cells make key proteins rather than just targeting genes. In the future, this could improve outcomes for children with high-risk neuroblastoma by slowing tumor growth and reducing relapse.