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, 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.
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.
Boutz PL, Chawla G, Stoilov P, Black DL. MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development. Genes Dev. 2007 Jan 1;21(1):71-84.
Boutz PL, Stoilov P, Li Q, Lin CH, Chawla G, Ostrow K, Shiue L, Ares M Jr, 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.
Black DL. Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem. 2003; 72: 291-336.