National Academy of Sciences
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Election Year: 2011
Primary Section: 21, Biochemistry
Membership Type: Member
My lab studies RNAs that regulate gene expression in animals, plants and yeast. We were among those to find that animals have many microRNAs, which are ~22-nt RNAs that specify gene repression by base-pairing to messages of protein-coding genes. We then found miRNAs in plants and have been developing increasingly reliable methods for identifying the regulatory targets of microRNAs in both plants and animals. Using these methods, we uncovered the widespread scope of microRNA-mediated regulation in animals, providing compelling evidence that most human genes are regulated by microRNAs. Our genome-wide approaches are also showing that miRNAs primarily act to decrease target mRNA levels, and experiments following-up on individual targeting interactions are revealing biological functions of microRNA action, such as how microRNAs play critical roles in plant development and how the interaction between a human microRNA and one of its regulatory targets helps prevent human cancers.
We also found several other types of regulatory RNAs, including heterochromatic siRNAs, which direct DNA silencing, and we did some of the early biochemical characterization of RNA interference (RNAi), which laid the groundwork for using synthetic small interfering RNAs (siRNAs) to knock down gene expression in mammalian cells. Our current work on RNAi focuses on the mechanism, evolution, and biological functions of this gene-silencing pathway in budding yeasts.
Prior to studying regulatory RNAs, my lab investigated the catalytic potential of RNA. For example, we generated a ribozyme that catalyzes the type of RNA-polymerization reaction needed for RNA replication, which supports the idea of an "RNA world" during the early evolution of life.