BLENCOWE LAB
UNIVERSITY OF TORONTO


Research Overview

Our research focuses on mechanisms underlying the regulation of gene expression and how these mechanisms are disrupted 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, biochemical, and cell biological 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 Review Articles

Raj and Blencowe 2015




Raj, B. and Blencowe, B.J (2015) Alternative splicing in the mammalian nervous system: recent insights into mechanisms and functional roles, Neuron, 81(1):14-27.

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Braunschweig et al. 2013




Braunschweig, U., Gueroussov, S., Plocik, A.M., Graveley, B.R. and Blencowe, B.J (2013) Dynamic integration of Splicing within Gene Regulatory Pathways, Cell, 152:1252-1269.

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Irimia and Blencowe, 2012




Irimia, M, Blencowe, B.J. (2012) Alternative splicing: decoding an expansive regulatory layer, Current Opinion in Cell Biology, 24: 3.

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Han, 2011




Han, H., Nutiu, R., Moffat, J. and Blencowe, B.J. (2011) SnapShot: High Throughput Sequencing Applications, Cell 146(6):1044-1044.e2.

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Blencowe, 2009




Blencowe, B.J., Ahmad, S. and Lee,L.J.(2009) Current generation high-throughput sequencing: deepening insights into mammalian transcriptomes, Genes and Development 23:1379-1386.

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Blencowe, 2006




Blencowe, B.J. (2006) Alternative Splicing: New insights from global analyses, Cell 126:37-47.

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Current Research Topics and Selected Publications

Deep surveying of transcriptome complexity, global mapping of RNA-RNA interactions and deciphering RNA regulatory codes

Sharma et al. 2016
Sharma, E., Sterne-Weiler, T., O'Hanlon, D. and Blencowe, B.J. (2016). Global Mapping of Human RNA-RNA Interactions. Mol. Cell. 62:618-626.

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-Highlighted in Molecular Cell and TIBS

Xiong et al. 2015
Xiong, H.Y., Alipanahi, B., Lee, L.J., Bretschneider, H., Merico, D., Yuen, R.K., Hua, Y., Gueroussov, S., Najafabadi, H.S., Hughes, T.R., Morris, Q., Barash, Y., Krainer, A.R., Jojic, N., Scherer, S.W., Blencowe, B.J. and Frey, B.J. (2015). The human splicing code reveals new insights into the genetic determinants of disease. Science. 347(6218):12.

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-Highlighted in Science Perspectives
-Featured in several media reports including The Globe and Mail and The Varsity.
-Recommended by Faculty of 1000

Braunschweig et al 2014
Braunschweig, U., Barbosa-Morais, N.L., Pan, Q., Nachman, E., Alipanahi, B., Gonatopoulos-Pourtnazis, T., Frey, B., Irimia, M. & Blencowe, B.J. (2014). Widespread intron retention in mammals functionally tunes transcriptomes. Genome Research, 24(11): 1774-1786.

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-Highlighted in Nature Reviews Genetics article

Barash et al 2010
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.

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-Featured in Nature Editorials, in several News and Views articles in Nature, Nature Biotech, Cell Res, and numerous media reports including CBC,and Toronto Star
-Featured on the journal cover
-Recommended by Faculty of 1000
-Featured in a Nature Biotech article "Trends in Computational Biology-2010"

Pan et al. 2008
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. Genetics. 40:1413-1415.

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-Highlighted in Nature and Nature Genetics Editorial, Research Highlight of Nature Review Genetics.
-Highlighted on the journal cover




Discovery and characterization of splicing regulators and exon networks with critical roles in development

Quesnel Vallieres et al. 2015
Quesnel-Vallieres, M., Irimia, M., Cordes, S.P. and Blencowe, B.J. (2015). Essential roles for the splicing regulator nSR100/SRRM4 during nervous system development. Genes and Development. 29(7):746-759.

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Raj et al. 2014
Raj, B., Irimia, M., Braunschweig, U., Sterne-Weiler, T., O’Hanlon, D., Lin, Z.Y., Chen, G.I., Easton, L., Ule, J., Gingras, AC., Eyras, E. and Blencowe, B.J. (2014). A global regulatory mechanism for activating an exon network required for neurogenesis. Molecular Cell. 56(1):90-103.

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Ellis et al. 2012
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.

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-Featured on the journal cover.
-Featured in Nature Reviews Genetics Editorial
Raj et al. 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.

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Saltzman et al. 2011
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.

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Calarco et al. 2009
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.

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-Recommended by Faculty of 1000.
-Featured in the UofT Faculty of Medicine News.


Regulation of embryonic stem cell-specific alternative and splicing reprogramming

Han et al 2013
Han, H., Irimia, I., Ross, P.J., Sung, H-K., Alipanahi, B., David, L., Golipour, A., Gabut, M., Michael, I.P., Nachman E.N., Wang, E., Trcka, D., Thompson, T., O'Hanlon, D., Slobodeniuc, V., Barbosa-Morais, N.L., Burge, C.B., Moffat, J., Frey, B.J., Nagy, A., Ellis, J., Wrana, J.L. and Blencowe, B.J. (2013) MBNL proteins repress ES-cell-specific alternative splicing and reprogramming. Nature,

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-Highlighted in Nature News and Views article and in Nature Reviews Molecular Cell Biology article.
-Recommended by Faculty of 1000.

Gabut et al. 2011
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.

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-Featured in Cell Preview Article and in Nature Reviews Genetics Research Highlights.
-Ranked among Top 10 "hottest" research articles in the fields of biochemistry, genetics and molecular biology in 2011
-Recommended by Faculty of 1000.



Role of epigenetic modifications and the transcriptional machinery in the regulation of alternative splicing

Ip et al. 2011
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.

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Luco et al. 2010
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.

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-Recommended by Faculty of 1000.
-Featured in Dev. Cell Editorial and Nature Journal Club



The evolutionary landscape of alternative splicing in vertebrate species

Gueroussov et al. 2015
Gueroussov, S., Gonatopoulos-Pournatzis, T., Irimia, M., Raj, B., Lin, Z.Y., Gingras, A.C. and Blencowe, B.J (2015) An alternative splicing event amplifies evolutionary differences between vertebrates. Science, 349: 868-873.

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-Recommended by Faculty of 1000.
Barbosa-Morais et al. 2012
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.

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-Featured in Science perspective article.
-Recommended by Faculty of 1000.
Calarco et al 2007
Calarco, J.A., Xing, Y., Caceres, M., Calarco, J.P., Xiao, X., Pan, Q., Lee, C., Preuss, T.M. and Blencowe, B.J., (2007) Global analysis of alternative splicing differences between human and chimpanzees. Genes and Dev. 21: 2963-2975.

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-Featured in CBC news and other media reports.
-Featured in Cell, Leading Edge: Genetics Select



Alternative splicing and human disease


Irimia et al. 2014
Irimia, M., Weatheritt, R.J., Ellis, J., Parikshak, N.N., Gonatopoulos-Pourtnazis, T., Babor, M., Quesnel-Vallieres, M., Tapial, J., Raj, B., O'Hanlon, D., Barrios-Rodiles, M., Sternberg, M.J.E., Cordes, S.P., Roth, F.P., Wrana, J.L., Geschwind, D.H. and Blencowe, B.J. (2014). A highly conserved program of neuronal microexons is misregulated in autistic brains. Cell. 159(7):1511-1523.

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-Featured in Cell Preview, EMBO Journal Preview article and Nature Reviews Neuroscience.
-Recommended by Faculty of 1000.
-Highlighted in Toronto Star and London Free Press newspaper articles
Misquitta et al. 2011
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 Biol., 31: 138-150.

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Voineagu et al. 2011
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

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-Featured in Nature, Nature Review Genetics and Nature Reviews Neuroscience Research highlights
-Recommended by Faculty of 1000.
-Highlighted in BBC, TIME and other International Media reports