Sharp Laboratory

RNA interference (RNAi) has dramatically expanded the possibilities for genotype/phenotype analysis in cell biology. Investigations into the mechanisms responsible for the activities of short interfering RNAs (siRNAs) are ongoing with the objective of increasing their effectiveness in gene silencing. Delivery of siRNAs by nanoparticles to silence genes in tumors is being tested in ovarian tumor models. MicroRNAs (miRNAs) are encoded by endogenous genes and regulate over half of all genes in mammalian cells. They regulate gene expression at the stages of translation and mRNA stability. Physically identifying the target mRNAs for particular miRNAs is of great interest. We are also investigating the relationship between gene regulation by miRNAs and cellular stress. The roles of small RNAs in embryonic stem cells and in lymphocytes are being investigated. We are also studying the nature of specific proteins important for regulation of alternative RNA splicing of the CD44 gene in normal and tumor cells.