Warren Winick-Ng is awarded the Robert Home Research Fellowship.
Efficient, specific, and combinatorial control of endogenous exon splicing with dCasRx-RBM25.
Li, J.D., Taipale, M., Blencowe, B.J. Molecular Cell. S1097-2765(24)00475-1. (2024).
In our most recent paper published in Molecular Cell, we performed a screen of human splicing factors fused to deactivated RfxCas13d (dCasRx) for guide RNA-programmable regulation of target exons. dCasRx-RBM25 was identified as an artificial splicing factor that can efficiently specifically and combinatorially activate or repress targeted endogenous exons, opening the door to new research and therapeutic applications. (read more).
Jacob Fine is awarded an Ontario Graduate Scholarship.
Jack Li is awarded the NSERC Canada Graduate Scholarship.
Kenny Rebelo is awarded the School of Graduate Studies Conference Grant.
Systematic analysis of alternative exon-dependent interactome remodeling reveals multitasking functions of gene regulatory factors .
In our most recent paper with Anne-Claude Gingras and colleagues, affinity purification coupled to mass spectrometry was used to explore how neural-differential alternative exons in transcription and chromatin regulators impact protein interactions. Our studies provides a resource of neural exon-regulated protein-protein interactions, and further uncovers roles for exons in Chtop and Sap30bp in controlling mRNA export through PRMT1-dependent methylation and mini-intron splicing, respectively (read more).
Kenny Rebelo is awarded an Ontario Graduate Scholarship.
Mackenzie Moore and Jacob Fine are awarded the Cecil Yip Doctoral Research Award (read more).
.Jacob Fine is awarded the Carelton E. Perrin Award and the NSERC Canada Graduate Scholarship.
Jack Li is awarded the Cecil Yip Doctoral Research Award (read more).
Steven Dupas wins Best Poster Prize for the 2022 Donnelly Retreat.
Systematic exploration of dynamic splicing networks reveals conserved multistage regulators of neurogenesis.
In our most recent paper published in Molecular Cell, we employ a Neu-SPAR-seq screen to discover factors that regulate spatiotemporal splicing networks associated with neurogenesis. Integration of the screen data with molecular characterization and single-cell transcriptomics reveals multistage roles for Rbm38 and Puf60 isoforms in the regulation of splicing patterns and establishment of neuronal identity.
Steven Dupas is awarded an NSERC Postgraduate Scholarship Doctoral Award.
Guillermo Parada is awarded the 2022 Charles H. Best Fellowship (read more).
Systematic mapping of nuclear domain-associated transcripts reveals speckles and lamina as hubs of functionally distinct retained introns.
Our most recent paper published in Molecular Cell, reports the first large-scale survey of RNA transcripts that are associated with different nuclear bodies. This work suggests that these structures acts as hubs to coordinate gene regulation and cell division (read more).
Ulrich Braunschweig is awarded the Donnelly Centre Research Excellence Award (read more).
Shagheyegh Farhangmehr is awarded the University of Toronto Open Scholarship.
Steven Dupas is awarded the Cecil Yip Doctoral Research Award.
Steven Dupas is awarded an NSERC Canada Doctoral Graduate Scholarship.
Kenny Rebelo is awarded the Cecil Yip Doctoral Research Award.
Shaghayegh Farhangmehr is awarded an Ontario Graduate Scholarship.
Thomas Gonatopoulos-Pournatzis accepts a prestigious Investigator position in the RNA Laboratory of the Center for Cancer Research at NIH, and will open his lab later this year.
Systematic multi-site genomic editing using a hybrid CRISPR-Cas platform reveals gene paralog interactions and essential alternative exons.
Gonatopoulos-Pournatzis, Aregger, Brown et al., Nature Biotech.38(5):638-6489. 2020.
Our most recent paper (involving a collaboration with Jason Moffat, Chad Myers and colleagues), describes a new functional genomics tool enabling the systematic mapping of genetic interactions and interrogation of the functions of sizable genomic segments in mammalian cells. Named ‘Cas Hybrid for Multiplexed Editing and screening Applications’ (CHyMErA), it outperforms genetic screens using Cas9 or Cas12a editing alone. Application of CHyMErA to the ablation of mammalian paralog gene pairs revealed extensive genetic interactions and uncovered phenotypes normally masked by functional redundancy. Application of CHyMErA in a chemogenetic interaction screen identified genes that impact cell growth in response to mTOR pathway inhibition. Moreover, by systematically targeting thousands of alternative splicing events, CHyMErA identified exons underlying human cell line fitness. CHyMErA thus represents an effective screening approach for genetic interaction mapping and the functional analysis of sizable genomic regions, such as alternative exons.
Justin Lim is awarded an NSERC Alexander Graham Bell Canada Doctoral Graduate Scholarship.
Autism-misregulated eIF4G microexons control synaptic translation and higher-order cognitive functions.
Gonatopoulos-Pournatzis et al. Molecular Cell.77(6):1176-1192. 2020.
In this paper, which arose through a collaboration with Sabine Cordes and several additional groups in Toronto, we characterized vertebrate-conserved neuronal microexons in the translation initiation factor eIF4G1 and eIF4G3 paralogs, which are regulated by SRRM4 and neuronal activity, and misregulated in autistic brains. Genetic ablation of these proteins results in increased expression of numerous proteins that impact synaptic transmission and plasticity. Mice deficient of the Eif4g1 microexon display altered social behavior and memory deficits, accompanied by an aberrant form of protein synthesis-dependent synaptic plasticity. The eIF4G microexons primarily regulate neuronal translation by promoting ribosome stalling, through a mechanism associated with the increased coalescence of numerous neuronal granule components, including the Fragile X mental retardation protein, FMRP. Mechanistic similarities by which the eIF4G microexons and FMRP control translation of synaptic protein expression provide an intriguing link between idiopathic cases of autism, in which pronounced eIF4G1 microexon skipping is often detected, and Fragile X syndrome. This work further suggests a novel potential therapeutic strategy for neurological disorders.
Zheng Luo is awarded the CH Best Postdoctoral Fellowship.
Alternative splicing regulatory networks: Functions, mechanisms, and evolution.
Ule and Blencowe. Molecular Cell. 76(2):329-345. 2019.
Latest review article on alternative splicing written with Jernej Ule at the Crick Institute.
Ben is elected Fellow of the Royal Society of London (UK).
Drice Challal is awarded an EMBO Postdoctoral Fellowship.
Autism spectrum disorder: insights into convergent mechanisms from transcriptomics.
Our latest review featured on the cover of Nature Reviews in Genetics.
Efficient and accurate quantitative profiling of alternative splicing patterns of any complexity on a laptop.
Our latest paper describes a powerful new method for analyzing alternative splicing using RNA-Seq data.
Thomas Gonatopoulos-Pournatzis is awarded the inaugural Donnelly Centre Research Excellence Award (read more).
Rasim Barutcu is awarded a Banting Postdoctoral Fellowship.
Eesha Sharma receives the Jennifer Dorrington Graduate Research Award (read more).
Serge Gueroussov receives the Barbara Vivash Award in Molecular Genetics for the most outstanding PhD thesis defended in 2017 (read more).
Please don't hesitate to contact us to learn more about the work in our lab.
Blencowe Lab
The Donnelly Centre
University of Toronto
160 College St, Rm 1030
Toronto, ON M5S 3E1
Canada
Ben: b -dot- blencowe -at- utoronto -dot- ca
Lab Manager: jonathan -dot- ellis -at- utoronto -dot- ca
Office: 416-978-3016
Lab: 416-978-7150
Fax: 416-946-5545