Dr. Douglas Black's lab is interested in the regulation of pre-mRNA splicing in neurons and the biochemical mechanisms that control changes in splice sites.
One major endeavor aims to identify splicing regulatory molecules and to determine their mechanisms of action. This uses the neural specific N1 exon of the c-src gene as a model for biochemistry.
A second major effort is directed at understanding how cell-signaling pathways impact the splicing reaction. This project focuses on the effect of cell excitation on the splicing of ion channel transcripts and the role of these splicing changes in neuronal plasticity.
Other interests within the lab include the development of oligonucleotide microarrays to assay splicing, examining the biological role of specific splicing factors in knockout mice, and understanding how the coupling of splicing to transcription affects splice site choice.
Selected Cancer-Related Publications:
Sharma S, Maris C, Allain FH, Black DL. U1 snRNA directly interacts with polypyrimidine tract-binding protein during splicing repression. Mol Cell. 2011 Mar 4;41(5):579-88.
Pandya-Jones A, Black DL. Co-transcriptional splicing of constitutive and alternative exons. RNA. 2009 Oct;15(10):1896-908. Epub 2009 Aug 5
Stoilov P, Lin CH, Damoiseaux R, Nikolic J, Black DL. A high-throughput screening strategy identifies cardiotonic steroids as alternative splicing modulators. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11218-23. Epub 2008 Aug 4.
Sharma S, Kohlstaedt LA, Damianov A, Rio DC, Black DL. Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome. Nat Struct Mol Biol. 2008 Feb;15(2):183-91. Epub 2008 Jan 13
Boutz PL, Stoilov P, Li Q, Lin CH, Chawla G, Ostrow K, Shiue L, Ares M, Black DL. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev. 2007 Jul 1;21(13):1636-52.