Cancer is marked by uncontrolled proliferation and inappropriate survival of damaged cells in the body. Interestingly, many processes used to direct the proper growth, differentiation, and cell death of tissues in the developing embryo, are identical to the genetic pathways that are perturbed in the cancerous state. Within the last five years, it has emerged that a newly discovered class of non-protein encoding RNAs, microRNAs (miRNAs), can function as tumor suppressor genes and oncogenes, factors which strictly control cellular growth. MiRNAs are small ~22 nucleotide non-coding RNAs and function to negatively regulate expression of their gene targets. MiRNAs typically bind to complementary sequences located in the 3’ untranslated region (3’ UTR) of their target protein-coding messenger RNAs (mRNAs) commonly resulting in translational inhibition and/or mRNA degradation.
My laboratory is very interested in studying how miRNAs control developmental events and how this relates to cancer progression. Specifically, the lab focuses on the lin-4 and let-7 miRNA families, which are found to direct important developmental processes such as cell-fate specification and gonad formation, and which are closely linked to human cancer. My lab employs the nematode, Caenorhabditis elegans, an organism easily grown and studied in the laboratory and amendable to genetic manipulation, to characterize the biological function of the lin-4 and let-7 miRNA homologues during development. We use the nematode as a tool for gene discovery to identify targets specifically regulated by these miRNA families to control cancer-associated processes. We are also investigating if these miRNAs and their targets are evolutionarily conserved and control similar proliferation pathways in mammals using both mouse models and mammalian cell culture. Furthermore, we intend to characterize the tumor suppressor role of the lin-4 and let-7 miRNA families in lung tumor formation and extend our findings to oncogenic pathways involved in urothelial cancers, primarily prostate cancer. Using both nematode and mammalian systems, our work promises to reveal miRNAs as a major class of cancer progression genes with immense therapeutic potential.