Our research focuses on mechanisms underlying the regulation of gene expression and how these mechanisms go awry in human diseases. Most of our research is directed at understanding how alternative splicing is regulated and integrated with other layers of gene expression to control fundamental biological processes. For example, we have recently discovered alternative splicing "switches" with key roles in the regulation of transcriptional programs required for neural cell differentiation, embryonic stem cell pluripotency, and which are important for efficient somatic cell reprogramming. Our research encompasses a wide range of approaches, from bioinformatics and functional genomics to focused molecular and biochemical methods. We have pioneered the development and application of technologies for the genome-wide quantitative profiling of transcriptomes. These efforts have uncovered a remarkable landscape of new regulation that awaits further investigation.
Selected Publications (Past Five Years Only)
Braunschweig, U., Gueroussov, S., Plocik, A.M., Graveley, B.R. and Blencowe, B.J (2013) Dynamic integration of Splciing within Gene Regulatory Pathways, Cell, 152:1252-1269. [MEDLINE] [PDF]
Barbosa-Morais, N.L., Irimia, M., Pan, Q., Xiong, H.Y., Gueroussov, S., Lee, L.J., Slobodeniuc, V., Kutter, C., Watt, S., Colak, R., Kim, T.H, Misquitta-Ali, C.M., Wilson, M.D., Kim, P.M., Odom, D.T., Frey, B.J. and Blencowe, B.J (2012) The evolutionary landscape of alternative splicing in vertebrate species, Science, 338: 1587-1593. [MEDLINE] [PDF]
Ellis, J.D., Barrios-Rodiles, M., Çolak, R., Irimia, M., Kim, T., Calarco, J.A., Wang, X., Pan, Q., O'Hanlon, D., Kim, P.M., Wrana, J.L., and Blencowe, B.J. (2012) Tissue-specific alternative splicing remodels protein-protein interaction networks. Molecular Cell. 46: 884-892. [MEDLINE] [PDF]
Irimia, M, Blencowe, B.J. (2012) Alternative splicing: decoding an expansive regulatory layer, Current Opinion in Cell Biology, 24: 323-332. [MEDLINE] [PDF]
Gabut, M., Samavarchi-Tehrani, P., Wang, X., Slobodeniuc, V., O'Hanlon, D., Sung, H.K., Alvarez, M., Talukder, S., Pan, Q., Mazzoni, E.O., Nedelec, S., Wichterle, H., Woltjen, K., Hughes, T.R., Zandstra, P.W., Nagy, A., Wrana, J.L., and Blencowe, B.J. (2011) An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. Cell, 147: 132-146. [MEDLINE] [PDF]
-Featured in Cell Preview Article by Brenton Graveley
-Ranked among Top 10 most highly downloaded research articles in the fields of biochemistry, genetics and molecular biology in 2011
Raj, B., O'Hanlon, D., Vessey, J.P., Pan, Q., Ray, D., Buckley, N.J., Miller, F.D., and Blencowe, B.J. (2011) Cross-regulation between an alternative splicing activator and a transcription repressor controls neurogenesis. Mol Cell, 43: 843-850. [MEDLINE] [PDF]
Voineagu, I., Wang, X., Johnston, P., Lowe, J., Tian, Y., Horvath, S., Mill, J., Cantor, R., Blencowe, B.J., and Geschwind, D. (2011) Transcriptome Analysis of Autistic Brain Reveals Convergent Molecular Pathology. Nature, 474: 380-400. [MEDLINE] [PDF]
Saltzman, A.L., Pan, Q., and Blencowe, B.J. (2011). Regulation of alternative splicing by the core spliceosomal machinery. Genes and Development, 25: 373-384. [MEDLINE] [PDF]
Ip, J.Y., Schmidt, D., Pan, Q., Ramani, A.K., Fraser, A.G., Odom, D.T., and Blencowe, B.J. (2011). Global impact of RNA polymerase II elongation inhibition on alternative splicing regulation. Genome Research, 21: 390-401. [MEDLINE] [PDF]
Misquitta-Ali, C.M., Cheng, E., O’Hanlon, D., Liu, N., McGlade, C.J., Tsao, M.S., and Blencowe, B.J. (2011). Global profiling and molecular characterization of alternative splicing events misregulated in lung cancer. Mol. Cell Bio., 31: 138-150. [MEDLINE] [PDF]
Barash, Y., Calarco, J.A., Gao, W., Pan, Q., Wang, X., Shai, O., Blencowe, B.J., and Frey, B.J. (2010). Deciphering the splicing code. Nature, 465: 53-59. [MEDLINE] [PDF]
-Featured on the journal cover
-Featured in Nature Journal editorials, in several News and Views articles and numerous media reports
-Faculty of 1000 "recommended" paper
Luco, R.F., Pan, Q., Tominaga, K., Blencowe, B.J., Pereira-Smith, O.M. and Misteli, T. (2010). Regulation of alternative splicing by histone modifications. Science, 327:996-1000. [MEDLINE] [PDF]
-Faculty of 1000 "Must Read" paper
-Featured in Dev. Cell Editorial
Calarco, J., Superina, S., O'Hanlon, D., Gabut, M., Raj, B., Pan, Q., Skalska, U., Clarke, L., Gelinas, D., van der Kooy, D., Zhen, M., Ciruna, B., and Blencowe, B.J. (2009). Regulation of Vertebrate Nervous System-Specific Alternative Splicing and Development by an SR-Related Protein. Cell, 138: 898-910. [MEDLINE] [PDF]
-Recommended by Faculty of 1000.
Pan, Q., Shai, O., Lee, L., Frey, B.J., and Blencowe, B.J. (2008). Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat. Genet. 40:1413-1415. [MEDLINE] [PDF]
-Highlighed in Nature and Nature Genetics editorials
-Featured on the journal cover
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