Professor Jennifer Mitchell

Jennifer A. Mitchell

Associate Professor


Campus

St. George (downtown)

CSB Appointment

Full

Research Areas

Animal Biology, Bioinformatics / Computational Biology, Developmental Biology, Genetics / Genomics, Molecular Biology, Systems Biology

Education

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

Titles and Honors

CIHR New Investigator

Dorothy Shoichet Women Faculty Award of Excellence 2016

Primary Undergraduate Department

Cell & Systems Biology

Graduate Programs

Cell & Systems Biology
Genome Biology and Bioinformatics

Academic or Administrative Appointments

Associate Chair, Research

Research Description

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.


Contact Information

Office Phone: 416-978-6711
Office: RW519A
Lab: RW519
Lab Phone: 416-978-6715
Email

Mailing Address

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

Visit lab’s website


Recent News

Transcriptional enhancers don’t require ‘master regulators’

A common assumption in studying gene transcription is that there are 'master regulators' that are required for gene regulation. Gurdeep Singh from…

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Dr Sakthi Moorthy chasing the dream to be a scientist from India to Canada

For International Women’s Day 2021, Cell & Systems Biology (CSB) is highlighting the scientists behind the science we publish, and the staff that…

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CSB Year in Review: Top Stories of 2020

As the year comes to a close, we look back on the achievements of students, staff, and faculty in the Cell and Systems Biology Department. Here are…

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Publications

2021

The recycling endosome protein Rab25 coordinates collective cell movements in the zebrafish surface epithelium.

Willoughby PM, Allen M, Yu J, Korytnikov R, Chen T, Liu Y, So I, Macpherson N, Mitchell JA, Fernandez-Gonzalez R, Bruce AE
2021, eLife, 10, 33755014

A flexible repertoire of transcription factor binding sites and a diversity threshold determines enhancer activity in embryonic stem cells

Singh G, Mullany S, Moorthy SD, Zhang R, Mehdi T, Tian R, Duncan AG, Moses AM, Mitchell JA
2021, Genome Research, 10.1101/gr.272468.120

Transcriptional control of parturition: insights from gene regulation studies in the myometrium

Khader N, Shchuka VM, Shynlova O, Mitchell JA
2021, Molecular Human Reproduction, 10.1093/molehr/gaab024

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2020

Enhancer-gene rewiring in the pathogenesis of Quebec platelet disorder.

Liang M, Soomro A, Tasneem S, Abatti LE, Alizada A, Yuan X, Uusküla-Reimand L, Antounians L, Alvi SA, Paterson AD, Rivard GÉ, Scott IC, Mitchell JA, Hayward CPM, Wilson MD
2020, Blood, 136, 2679-2690, 32663239

Transcriptional enhancers: from prediction to functional assessment on a genome-wide scale

Tobias IC, Abatti LE, Moorthy SD, Mullany S, Taylor T, Khader N, Filice MA, Mitchell JA
2020, Genome, 10.1139/gen-2020-0104

The pregnant myometrium is epigenetically activated at contractility-driving gene loci prior to the onset of labor in mice

Rivera RM, Shchuka VM, Abatti LE, Hou H, Khader N, Dorogin A, Wilson MD, Shynlova O, Mitchell JA
2020, PLOS Biology, 10.1371/journal.pbio.3000710

Genes responsive to rapamycin and serum deprivation are clustered on chromosomes and undergo reorganization within local chromatin environments

Belak ZR, Pickering JA, Gillespie ZE, Audette G, Eramian M, Mitchell JA, Bridger JM, Kusalik A, Eskiw CH
2020, Biochemistry and Cell Biology, 10.1139/bcb-2019-0096

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2019

KLF4 protein stability regulated by interaction with pluripotency transcription factors overrides transcriptional control.

Dhaliwal NK, Abatti LE, Mitchell JA
2019, Genes & development, 31221664

Pluripotency on Lockdown after Deletion of Three Transcription Regulators.

Mitchell JA
2019, Cell stem cell, 24, 681-683, 31051130

Variational Infinite Heterogeneous Mixture Model for Semi-supervised Clustering of Heart Enhancers.

Mehdi TF, Singh G, Mitchell JA, Moses AM
2019, Bioinformatics (Oxford, England), 30753279

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2018

KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency.

Dhaliwal NK, Miri K, Davidson S, Tamim El Jarkass H, Mitchell JA
2018, Stem cell reports, 10, 1308-1323, 29526737

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2016

Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genes.

Moorthy SD, Davidson S, Shchuka VM, Singh G, Malek-Gilani N, Langroudi L, Martchenko A, So V, Macpherson NN, Mitchell JA
2017, Genome research, 27, 246-258, 27895109

Generating CRISPR/Cas9 Mediated Monoallelic Deletions to Study Enhancer Function in Mouse Embryonic Stem Cells.

Moorthy SD, Mitchell JA
2016, Journal of visualized experiments : JoVE, e53552, 27078492

Nuclear RNA Isolation and Sequencing.

Dhaliwal NK, Mitchell JA
2016, Methods in molecular biology (Clifton, N.J.), 1402, 63-71, 26721484

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2015

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
2015, Royal Society open science, 2, 150402, 26473061

Chromatin Dynamics in Lineage Commitment and Cellular Reprogramming

Shchuka VM, Malek-Gilani N, Singh G, Langroudi L, Dhaliwal NK, Moorthy SD, Davidson S, Macpherson NN, Mitchell JA
2015, Genes, 6, 641-61, 26193323

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
2015, Genome research, 25, 582-97, 25752748

Rapamycin reduces fibroblast proliferation without causing quiescence and induces STAT5A/B-mediated cytokine production.

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
2015, Nucleus (Austin, Tex.), 6, 490-506, 26652669

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2014

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
2014, Genes & development, 28, 2699-711, 25512558

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2013

Nuclear organization of RNA polymerase II transcription

Davidson S, Macpherson N, Mitchell JA
2013, Biochemistry and cell biology = Biochimie et biologie cellulaire, 91, 22-30, 23442138

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2012

Upstream distal regulatory elements contact the Lmo2 promoter in mouse erythroid cells

Bhattacharya A, Chen CY, Ho S, Mitchell JA
2012, PloS one, 7, e52880, 23285212

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
2012, PloS one, 7, e49274, 23209567

Sensitive detection of chromatin coassociations using enhanced chromosome conformation capture on chip

Sexton T, Kurukuti S, Mitchell JA, Umlauf D, Nagano T, Fraser P
2012, Nature protocols, 7, 1335-50, 22722369

Enhancer identification in mouse embryonic stem cells using integrative modeling of chromatin and genomic features

Chen CY, Morris Q, Mitchell JA
2012, BMC genomics, 13, 152, 22537144

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2009

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
2010, Nature genetics, 42, 53-61, 20010836

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2008

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
2008, Science (New York, N.Y.), 322, 1717-20, 18988810

Transcription factories are nuclear subcompartments that remain in the absence of transcription

Mitchell JA, Fraser P
2008, Genes & development, 22, 20-5, 18172162

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2007

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
2007, PLoS biology, 5, e192, 17622196

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
2007, PloS one, 2, e630, 17637845

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2005

Replication and transcription: shaping the landscape of the genome

Chakalova L, Debrand E, Mitchell JA, Osborne CS, Fraser P
2005, Nature reviews. Genetics, 6, 669-77, 16094312

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2004

Differential activation of the connexin 43 promoter by dimers of activator protein-1 transcription factors in myometrial cells

Mitchell JA, Lye SJ
2005, Endocrinology, 146, 2048-54, 15618352

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
2004, Nature genetics, 36, 1065-71, 15361872

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
2004, American journal of physiology. Endocrinology and metabolism, 287, E439-45, 15126239

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2003

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
2004, Biology of reproduction, 70, 986-92, 14645109

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
2003, Biology of reproduction, 69, 556-62, 12700188

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2002

Differential expression of activator protein-1 transcription factors in pregnant rat myometrium

Mitchell JA, Lye SJ
2002, Biology of reproduction, 67, 240-6, 12080023

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