Our goal is to understand the mechanism and regulation of nuclear pre-mRNA splicing, an essential step in eukaryotic gene expression. Pre-mRNA splicing is catalyzed by a massive multimegadalton ribonucleoprotein machine called the spliceosome. Using the model organism S. cerevisiae as well as human cells, we apply a wide array of approaches, ranging from single molecule microscopy, biophysics, and chemical biology to biochemistry and cell biology to genetics and genomics to gain a deep understanding of how the spliceosome catalyzes and regulates pre-mRNA splicing, including in the context of transcription.
University of California at San Francisco (Advisor: Christine Guthrie)
San Francisco, CA
Postdoc - Biochemistry/Genetics
1999
Massachusetts Institute of Technology (Advisor: Peter S. Kim)
Boston, MA
Ph.D. - Chemistry/Biophysics
1993
Haverford College
Haverford, PA
B.A. - Chemistry
1987
Elevated levels of intracellular RNA lariats suppress the antiviral response.
Elevated levels of intracellular RNA lariats suppress the antiviral response. bioRxiv. 2024 Dec 08.
PMID: 39677789
Global impact of unproductive splicing on human gene expression.
Global impact of unproductive splicing on human gene expression. Nat Genet. 2024 Sep; 56(9):1851-1861.
PMID: 39223315
The debranching enzyme Dbr1 regulates lariat turnover and intron splicing.
The debranching enzyme Dbr1 regulates lariat turnover and intron splicing. Nat Commun. 2024 May 30; 15(1):4617.
PMID: 38816363
Global impact of aberrant splicing on human gene expression levels.
Global impact of aberrant splicing on human gene expression levels. bioRxiv. 2023 Oct 16.
PMID: 37745605
The debranching enzyme Dbr1 regulates lariat turnover and intron splicing.
The debranching enzyme Dbr1 regulates lariat turnover and intron splicing. Res Sq. 2023 Jun 13.
PMID: 37398028
Profiling lariat intermediates reveals genetic determinants of early and late co-transcriptional splicing.
Profiling lariat intermediates reveals genetic determinants of early and late co-transcriptional splicing. Mol Cell. 2022 12 15; 82(24):4681-4699.e8.
PMID: 36435176
Termination of pre-mRNA splicing requires that the ATPase and RNA unwindase Prp43p acts on the catalytic snRNA U6.
Termination of pre-mRNA splicing requires that the ATPase and RNA unwindase Prp43p acts on the catalytic snRNA U6. Genes Dev. 2019 11 01; 33(21-22):1555-1574.
PMID: 31558568
Structure of the DEAH/RHA ATPase Prp43p bound to RNA implicates a pair of hairpins and motif Va in translocation along RNA.
Structure of the DEAH/RHA ATPase Prp43p bound to RNA implicates a pair of hairpins and motif Va in translocation along RNA. RNA. 2017 07; 23(7):1110-1124.
PMID: 28416566
Specific Recognition of a Single-Stranded RNA Sequence by a Synthetic Antibody Fragment.
Specific Recognition of a Single-Stranded RNA Sequence by a Synthetic Antibody Fragment. J Mol Biol. 2016 10 09; 428(20):4100-4114.
PMID: 27593161
The Evolutionarily-conserved Polyadenosine RNA Binding Protein, Nab2, Cooperates with Splicing Machinery to Regulate the Fate of pre-mRNA.
The Evolutionarily-conserved Polyadenosine RNA Binding Protein, Nab2, Cooperates with Splicing Machinery to Regulate the Fate of pre-mRNA. Mol Cell Biol. 2016 11; 36(21):2697-2714.
PMID: 27528618
Fellow
American Association for the Advancement of Science
2016
Distinguished Investigator Award, Biological Sciences Division
The University of Chicago
2014
Stephen F. Sener, M.D. - Research Scholar Award
American Cancer Society
2006 - 2008
David & Lucile Packard Fellowship in Science and Engineering
Packard Foundation
2001 - 2006
Young Investigator Award
Cancer Research Foundation
2000 - 2001