Genetic information flows from DNA to messenger RNA, and then to protein. In cancer, one of the hallmarks is DNA rearrangement, which results in the fusion of two separate genes. These gene fusion products often play critical roles in cancer development. Traditionally, they are thought to be the sole product of DNA rearrangement, but Li recently discovered another mechanism that could generate the same fusion product without DNA rearrangement. This process is called “RNA trans-splicing,” whereby two separate RNAs can be spliced together and generate a fusion RNA, which then is translated into a fusion protein. Li’s goal is to understand the physiological functions of such RNA trans-splicing process and its implications in cancer. He will indentify examples of trans-spliced RNAs in normal and cancer cells, and validate the candidates identified through these approaches. Stem cell differentiation could shed light on the cells of origin for some mysterious cancers. Because of the broadness of gene fusions in cancer, Li’s discovery has already raised concerns for false positive cancer diagnoses with current diagnostic methods, as well as for potential side effects in normal tissues caused by therapies targeting these fusion protein products. Li hopes to better characterize the trans-splicing process, and translate this knowledge into better diagnostic and therapeutic approaches.
Hui Li, Ph.D., is assistant professor of pathology at the University of Virginia in Charlottesville, Va.
Updated: April 4, 2011