Jeffrey A. Pleiss
Jeff Pleiss received his B.A. in Chemistry at Northwestern University where he worked with Tobin Marks in the field of organometallic chemistry. Jeff's graduate work was completed in the lab of Olke Uhlenbeck at the University of Colorado, Boulder where he learned biochemical and biophysical techniques for studying the biology of RNA. Jeff was then supported as a fellow of the Damon Runyon Cancer Research Foundation for his work in Christine Guthrie's lab at the University of California, San Francisco. Here, Jeff combined the power of yeast genetics with nascent genomics tools to examine mechanisms by which RNA processing can function to regulate gene expression. In 2007 Jeff joined the Department of Molecular Biology and Genetics at Cornell University, where he combines biochemistry, biophysics, molecular biology, genetics, and high-throughput genomics to elucidate pathways in RNA biology that are critical for eukaryotic gene expression. Jeff's work is funded by the National Institutes of Health and the American Cancer Society.
The coding regions of most eukaryotic genes are interrupted by non-coding introns which must be removed from the pre-mRNA prior to translation. We are taking genome-wide approaches to (1) identify the different conditions under which this process is used as a control point for regulating gene expression, and (2) determine the mechanisms by which this control is manifested. During my post-doctoral work, prior to my arrival at Cornell, I developed microarrays that allowed me to examine pre-mRNA splicing from a genome-wide perspective in the budding yeast, Saccharomyces cerevisiae. The yeast genome is relatively devoid of introns, containing only ~ 300 introns in its ~6000 genes (the human genome, by comparison, has over 250,000 introns). Furthermore, yeast appeared to lack many of the features associated with alternative splicing in higher systems. As such, it had previously been widely believed that yeast lacked the capacity to regulate pre-mRNA splicing in a transcript specific fashion. However, by systematically examining the global changes in pre-mRNA splicing in response to changing environmental conditions, I was able to demonstrate that this process could be utilized as an important regulatory control point. This important finding demonstrates that mechanisms exist by which changes in external environment can be sensed by the organism and can lead to rapid and specific changes in the activity of this process. We are now aggressively examining how widely this regulatory paradigm is used, as well as its mechanistic underpinnings. In addition to our work in budding yeast, we are expanding this work into organisms with more complex intron architecture, including the fission yeast Schizosaccharomyces pombe.