Diplom (Chemistry) University des Saarlandes, Saarbruecken, Germany, 1986
Ph.D. (Biophysics & Biochemistry) Yale University, 1990
Postdoctoral: University of Colorado at Boulder
Research topics: Functional genomics and biology of tRNA, RNA epigenetics
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 and high-throughput sequencing methods that measure tRNA abundance, fraction of aminoacylation, misacylation and modification dynamics at the transcriptomic 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. We are investigating how regulated mis-translation is used as a mechanism for stress response and adaptation.
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 transcriptomic methods and applying these to study the function of RNA modifications in cell growth, adaptation and development.