Dr. Maura McGrail, Assistant Professor in GDCB, was awarded a sponsored grant of $139,360 from the National Cancer Institute of the National Institutes of Health for the research project “Sleeping Beauty transposon system for mutagenesis in zebrafish.” The grant will support the continued development of the zebrafish transposon system for identification of cancer genes that promote tumor formation and metastasis. The long-term goal of the project is to understand how misregulation of the genome leads to metastatic behavior of individual cancer cells, in order to identify new therapeutic targets.

The U.S. has seen a steady decline in cancer mortality rates since 1993, but the overall decrease is relatively slight, due in part to insufficient treatment strategies for invasive and metastatic disease. This stems in part from our incomplete understanding of the genetic changes that promote metastatic behavior in cancer cells. Gaining a functional understanding of the cancer genome has been further complicated by the discovery of thousands of noncoding genes expressed from the human genome. Understanding the function of the noncoding genome in normal development and disease is proceeding at a rapid pace, but is incomplete, and far less is known of its role in cancer.

Dr. McGrail previously developed the Sleeping Beauty system for somatic mutagenesis in zebrafish. The system uses transposons engineered to create mutations in genes that mimic those found in human cancer. The proposed project will adapt the Sleeping Beauty system to identify coding and noncoding genes that promote malignancy in a zebrafish model of brain cancer. This knowledge is expected to provide insight into the mechanisms underlying human brain cancer and reveal new molecular targets for treating malignant disease.