- Professor, Department of Biochemistry and Molecular Biology, Committee on Microbiology
Ph.D., Yale University, 1990
Diplom, University des Saarlandes, 1986
The University of Chicago
929 East 57th Street
Chicago, Illinois 60637
Lab: GCIS W125
Phone: (773) 702-4179
Lab: (773) 702-4680
Biology of Mistranslation , RNA Epigenetics, RNA Folding
Translational regulation is related to the dynamic properties of tRNA that constantly change to facilitate stress response and adaptation to new environments and to control gene expression. We developed microarray methods that measure tRNA abundance, fraction of aminoacylation and misacylation at the genomic scale. We are exploring roles of tRNA in translational control in mammalian cells.
A central tenet of biology is the accurate flow of information from nucleic acids to proteins through the genetic code. It is commonly believed that translation deviating from the genetic code is avoided at all times. We discovered that mammalian cells can deliberately reprogram the genetic code through tRNA misacylation upon innate immune activation and chemically triggered oxidative stress. The reprogramming is regulated by fluctuating levels of reactive oxygen species (ROS) in the cell. We are investigating how regulated mis-translation is used as a mechanism for stress response.
Over 100 types of post-transcriptional RNA modifications have been identified in thousands of sites from bacteria to humans. They include methylation of bases and the ribose backbone, rotation and reduction of uridine, base deamination, addition of ring structures and carbohydrate moieties, and so on. RNA modifications are involved in stress response, environmental adaptation, and antibiotic resistance. Some modifications can be removed by cellular enzymes, leading to dynamic regulation of their function. We are developing genome-wide methods and applying these to study the function of RNA modifications in cell growth, adaptation and development.
Non-coding RNAs perform biological function without being translated into proteins. Some estimates suggest that in human, the number of non-coding RNAs may be comparable to the number of coding RNAs. We are investigating how RNA folds during transcription to understand RNA folding in the cell.