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
Cryptic splicing mediates genetic and therapeutic perturbation of human gene expression levels.
Cryptic splicing mediates genetic and therapeutic perturbation of human gene expression levels. bioRxiv. 2023 Sep 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
Reverse transcriptases lend a hand in splicing catalysis.
Reverse transcriptases lend a hand in splicing catalysis. Nat Struct Mol Biol. 2016 06 07; 23(6):507-9.
PMID: 27273636
Cancer therapies activate RIG-I-like receptor pathway through endogenous non-coding RNAs.
Cancer therapies activate RIG-I-like receptor pathway through endogenous non-coding RNAs. Oncotarget. 2016 May 03; 7(18):26496-515.
PMID: 27034163
Spliceosomal DEAH-Box ATPases Remodel Pre-mRNA to Activate Alternative Splice Sites.
Spliceosomal DEAH-Box ATPases Remodel Pre-mRNA to Activate Alternative Splice Sites. Cell. 2016 Feb 25; 164(5):985-98.
PMID: 26919433
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