Jennifer A. Mitchell

faculty_img Academic Title: Associate Professor

Campus: St. George

CSB Appointment: Full

Primary Undergraduate Department:
Cell and Systems Biology

Graduate Programs:
Cell and Systems Biology
Genome Biology and Bioinformatics

Titles and Honors:
CIHR new investigator

Academic or Administrative Appointments

Education:
Ph.D. University of Toronto
B.Sc. University of Waterloo

 

Mailing Address
Department of Cell & Systems Biology
University of Toronto
25 Harbord St.
Toronto, ON M5S 3G5
Canada

 

Contact Information
Office phone: 416-978-6711
Office: RW 533A
Lab: RW 532 / 533
Lab phone: 416-978-6715
Email: ja.mitchell@utoronto.ca
URL: http://labs.csb.utoronto.ca/mitchell

 

Research Areas
Functional Genomics
Molecular Biology
Bioinformatics & Computational Biology
Developmental Biology

 

Research

How does our genome regulate the process of development and cell-type specialisation? Specific genes are expressed at discrete times due to the activation or repression of DNA regulatory regions. Our research investigates how the genome functions in stem cells to regulate self-renewal and differentiation. We often think about transcription as occurring on a particular gene in a linear manner whereas the nucleus is a three dimension organelle into which the genome is folded and organised. Within this folded structure DNA regulatory sequences physically contact the genes they regulate forming tissue-specific chromatin loops. We use CRISPR Genome Editing, Molecular Biology and Cellular Imaging techniques combined with Genome-Wide Sequencing approaches and Bioinformatics analysis to investigate the mechanisms that underlie tissue-specific regulation of gene expression and genome folding. Our previous work has identified the enhancers that activate numerous genes in stem cells including a distal enhancer of the Sox2 transcription factor which is required to maintain the stem cell state. The work we do provides a deeper understanding of how our DNA makes us unique and predisposes us to particular diseases. Our work also identifies new ways to consider treating genetic diseases with CRISPR Genome or Epigenome Editing.

 

Publications

 

 

2018

Top

KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency. Dhaliwal NK, Miri K, Davidson S, Tamim El Jarkass H, Mitchell JA. Stem Cell Reports. 2018 Apr 10;10(4):1308-1323. doi: 10.1016/j.stemcr.2018.02.007. Epub 2018 Mar 8.
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2017

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Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genesMoorthy SD, Davidson S, Shchuka VM, Singh G, Malek-Gilani N, Langroudi L, Martchenko A, So V, Macpherson NN and Mitchell JA. Genome Res. 2017 Feb;27(2):246-258. doi: 10.1101/gr.210930.116. Epub 2016 Nov 28.
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2016

Top

Generating CRISPR/Cas9 Mediated Monoallelic Deletions to Study Enhancer Function in Mouse Embryonic Stem Cells J Vis Exp 2016, (110), e53552Moorthy SD, Mitchell JA.
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Nuclear RNA Isolation and Sequencing.Methods Mol Biol. 2016;1402:63-71.Dhaliwal NK, Mitchell JA
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2015

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Rapamycin reduces fibroblast proliferation without causing quiescence and induces STAT5A/B-mediated cytokine production. Nucleus 2015, 6(6):490-506.Gillespie ZE, MacKay K, Sander M, Trost B, Dawicki W, Wickramarathna A, Gordon J, Eramian M, Kill IR, Bridger JM, Kusalik A, Mitchell JA, Eskiw CH.
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Concordance between RNA-sequencing data and DNA microarray data in transcriptome analysis of proliferative and quiescent fibroblasts.Trost B, Moir CA, Gillespie ZE, Kusalik A, Mitchell JA, Eskiw CH. R Soc Open Sci. 2015 Sep 30;2(9):150402
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The pluripotent regulatory circuitry connecting promoters to their long-range interacting elements.Schoenfelder S, Furlan-Magaril M, Mifsud B, Tavares-Cadete F, Sugar R, Javierre BM, Nagano T, Katsman Y, Sakthidevi M, Wingett SW, Dimitrova E, Dimond A, Edelman LB, Elderkin S, Tabbada K, Darbo E, Andrews S, Herman B, Higgs A, LeProust E, Osborne CS, Mitchell JA, Luscombe NM, Fraser P.Genome Res. 2015 Apr;25(4):582-97
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2014

Top

A Sox2 distal enhancer cluster regulates embryonic stem cell differentiation potential.Zhou HY, Katsman Y, Dhaliwal NK, Davidson S, Macpherson NN, Sakthidevi M, Collura F, Mitchell JA.Genes Dev. 2014 Dec;28(24):2699-711
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2013

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Nuclear organization of RNA polymerase II transcription.Davidson S, Macpherson N, Mitchell JA.Biochem. Cell Biol. 2013 Feb;91(1):22-30
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2012

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Upstream distal regulatory elements contact the Lmo2 promoter in mouse erythroid cells.Bhattacharya A, Chen CY, Ho S, Mitchell JA.PLoS ONE 2012;7(12):e52880
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Nuclear RNA sequencing of the mouse erythroid cell transcriptome.Mitchell JA, Clay I, Umlauf D, Chen CY, Moir CA, Eskiw CH, Schoenfelder S, Chakalova L, Nagano T, Fraser P.PLoS ONE 2012;7(11):e49274
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Sensitive detection of chromatin coassociations using enhanced chromosome conformation capture on chip.Sexton T, Kurukuti S, Mitchell JA, Umlauf D, Nagano T, Fraser P.Nat Protoc 2012 Jul;7(7):1335-50
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Enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic features.Chen CY, Morris Q, Mitchell JA.BMC Genomics 2012;13:152
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2010

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Preferential associations between co-regulated genes reveal a transcriptional interactome in erythroid cells.Schoenfelder S, Sexton T, Chakalova L, Cope NF, Horton A, Andrews S, Kurukuti S, Mitchell JA, Umlauf D, Dimitrova DS, Eskiw CH, Luo Y, Wei CL, Ruan Y, Bieker JJ, Fraser P.Nat. Genet. 2010 Jan;42(1):53-61
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2008

Top

The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin.Nagano T, Mitchell JA, Sanz LA, Pauler FM, Ferguson-Smith AC, Feil R, Fraser P.Science 2008 Dec;322(5908):1717-20
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Transcription factories are nuclear subcompartments that remain in the absence of transcription.Mitchell JA, Fraser P.Genes Dev. 2008 Jan;22(1):20-5
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2007

Top

Intergenic transcription, cell-cycle and the developmentally regulated epigenetic profile of the human beta-globin locus.Miles J, Mitchell JA, Chakalova L, Goyenechea B, Osborne CS, O’Neill L, Tanimoto K, Engel JD, Fraser P.PLoS ONE 2007;2(7):e630
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Myc dynamically and preferentially relocates to a transcription factory occupied by Igh.Osborne CS, Chakalova L, Mitchell JA, Horton A, Wood AL, Bolland DJ, Corcoran AE, Fraser P.PLoS Biol. 2007 Aug;5(8):e192
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2005

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Replication and transcription: shaping the landscape of the genome.Chakalova L, Debrand E, Mitchell JA, Osborne CS, Fraser P.Nat. Rev. Genet. 2005 Sep;6(9):669-77
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Differential activation of the connexin 43 promoter by dimers of activator protein-1 transcription factors in myometrial cells.Mitchell JA, Lye SJ.Endocrinology 2005 Apr;146(4):2048-54
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2004

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Active genes dynamically colocalize to shared sites of ongoing transcription.Osborne CS, Chakalova L, Brown KE, Carter D, Horton A, Debrand E, Goyenechea B, Mitchell JA, Lopes S, Reik W, Fraser P.Nat. Genet. 2004 Oct;36(10):1065-71
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Mechanical stretch and progesterone differentially regulate activator protein-1 transcription factors in primary rat myometrial smooth muscle cells.Mitchell JA, Shynlova O, Langille BL, Lye SJ.Am. J. Physiol. Endocrinol. Metab. 2004 Sep;287(3):E439-45
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Progesterone and gravidity differentially regulate expression of extracellular matrix components in the pregnant rat myometrium.Shynlova O, Mitchell JA, Tsampalieros A, Langille BL, Lye SJ.Biol. Reprod. 2004 Apr;70(4):986-92
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2003

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Parathyroid hormone-related protein treatment of pregnant rats delays the increase in connexin 43 and oxytocin receptor expression in the myometrium.Mitchell JA, Ting TC, Wong S, Mitchell BF, Lye SJ.Biol. Reprod. 2003 Aug;69(2):556-62
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2002

Top

Differential expression of activator protein-1 transcription factors in pregnant rat myometrium.Mitchell JA, Lye SJ.Biol. Reprod. 2002 Jul;67(1):240-6
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