The Brooks lab will explore how changes in RNA splicing alter the activity of genes associated with cancer. Before RNA molecules direct the synthesis of proteins, they are first spliced—a process that removes intervening genetic material and leaves behind only those sequences that code for protein. Mutations in the gene U2AF1, a component in the splicing system, are frequently observed in cancer; however, how these mutations lead to cancer is still unclear. As a postdoctoral fellow, I discovered that in cancer cells with such mutations, many RNAs are aberrantly spliced—some missing entire segments of protein-coding sequence. Now, using a suite of methods in next-generation sequencing, biochemistry, and molecular and computational biology, our lab will determine the sequences of all RNA transcripts produced by cells with mutated U2AF1. We will assess whether alternatively spliced RNA transcripts continue to direct the synthesis of proteins and what effect these RNAs have on the activity of genetic and cellular pathways. These findings will advance our understanding of how changes in RNA processing affect cell function and could lead to novel approaches for treating diseases, including cancers, in which splicing is abnormal.