Funded Research

Targeting an Rna Surveillance Pathway in Pediatric Cancer
Principal Investigator(s):
  • Zhongsheng You, Ph.D. Cell Biology and Physiology Visit Website
  • David R. Piwnica-Worms, M.D., Ph.D. Radiology
  • McDonnell Pediatric Cancer Center
Award Mechanism:
Interdisciplinary Research Initiative
Project Period:
2/1/2012 - 1/31/2013
Total Amount:
Joshua B. Rubin
Brain tumors in children represent a major challenge for cancer treatment. Cancer is mainly caused by mutations in DNA, which either turn expression of genes on or off or generate protein products with abnormal functions. Nonsense-mediated messenger RNA decay (NMD) is a surveillance system that detects and eliminates defective messenger RNAs that would otherwise produce truncated protein products. Recent research suggests that NMD plays an important role in cancer and may be a promising target for cancer treatment. To determine the relevance of NMD in pediatric brain cancer and to exploit the NMD pathway in cancer treatment, we have recently developed a novel bioluminescence-based reporter system that can quickly and accurately analyze NMD in cells. Building on this new technology, we will use this reporter to carry out the following basic and translational studies on NMD and pediatric brain cancer. Aims: 1) Detect potential differences between NMD in brain tumor cells and normal cells. We will also determine whether the identified NMD drugs can selectively killed tumor cells in cultured dishes and in mouse models that mimic brain tumors in children. Potential impact: Identification of NMD defects in pediatric brain tumors will provide new insights into the underlying molecular defects leading to brain tumors as well as new potential therapeutic targets. In turn, possible therapies for abnormal NMD may be identified by the small molecule inhibitor screens and basic studies on NMD pathway genes. If successful, clinical translation could occur as early as within 10 years.