Research Summary: What we do...
Normal cellular function requires that each protein in the cell is expressed at a specific level that is tuned to maintain cellular homeostasis. Nearly every disease is caused by, or is associated with, deregulated control of protein expression. The focus of our laboratory is to uncover how protein expression is regulated in normal cells and how it goes wrong in disease.
Every protein is encoded by a messenger RNA. However, not every mRNA is translated into protein with equal efficiency. The cell has intricate pathways that determine the amount of protein generated from any given mRNA.
We are discovering the ways that the cell regulates protein expression from mRNA. In 2012, we advanced the concept of mRNA regulation by "epitranscriptomic" modification, i.e., the control of mRNA fate by chemical modifications of nucleotides in mRNA. We developed a technology to globally profile a chemically modified nucleotide, N6-methyladenosine (m6A). This method, called MeRIP-Seq, demonstrated that chemically modified bases were widespread throughout the transcriptome, dynamically regulated during development and disease, and have regulatory potential. This work is often described as the study that launched the resurgence of interest in epitranscriptomics. MeRIP-Seq has been used by us and others to show that epitranscriptomic changes are critical for normal cellular development and mediate diverse disease processes, including cancer.
In addition to understanding basic mechanisms that control protein expression, a major mission of our laboratory is the development of novel enabling technologies for revealing new principles of RNA biology. These have included novel proteomic and computational techniques, as well as chemical biology tools for imaging RNA and RNA biology in cells. These include RNA aptamer tools for imaging RNA and signaling events in live cells. We have developed a series of RNA aptamers that bind and activate the fluorescence of other wise nonfluorescent small molecules. RNA-small molecule interactions and using synthetic biology approaches to develop RNA molecules with novel functions. We created a class of "RNA mimics of green fluorescent protein," most notably Spinach, which comprises a specific RNA aptamer and a small molecule dye whose fluorescence is switched on upon binding the RNA. We are developing novel RNA-fluorophore complexes with novel spectral properties for studying RNA trafficking and for developing tools to image RNA processing events in living cells.
The Jaffrey laboratory is a unique environment for making discoveries. Our laboratory brings together molecular biologists, chemists, and computational biologists to create a highly interdisciplinary environment for uncovering new principles in RNA biology. Our lab is situated in Manhattan, New York, adjacent to the Rockefeller University and Sloan Kettering Institute. This “tri-institutional campus” provides a rich scientific environment that is conducive for cutting-edge research. We welcome applications from scientists eager to join the lab and study these emerging areas of RNA biology.