Steven Pollard

- Centre for Regenerative Medicine
- Cancer Research UK Edinburgh Centre
Contact details
- Tel: 0131 651 9500
- Email: steven.pollard@ed.ac.uk
Address
- Street
-
Centre for Regenerative Medicine
Institute for Regeneration and Repair
The University of Edinburgh
Edinburgh BioQuarter
5 Little France Drive - City
- Edinburgh
- Post code
- EH16 4UU
Background
- 2013 – present Group Leader, MRC Centre for Regenerative Medicine and Edinburgh Cancer Research Centre, University of Edinburgh
- 2009–2013 Group Leader, Samantha Dickson Brain Cancer Unit and UCL Cancer Institute
- 2006–2009 Beit Memorial Research Fellow and Kaye Fellow (Christ’s College), with Austin Smith, Wellcome Trust Centre for Stem Cell Research, University of Cambridge Neural stem cells and brain cancer
- 2002-2006 Postdoc with Prof Austin Smith FRS, Institute for Stem Cell Research, University of Edinburgh Conversion of pluripotent ES cells to multipotent NS cells.
- 1998–2002 PhD student with Dr Derek Stemple, Division of Developmental Biology, MRC National Institute for Medical Research, Mill Hill, London Molecular genetics of zebrafish early development.
- 1997 (summer) Research internship, Dept Developmental Neurobiology, St Jude Children’s Research Hospital, Memphis, USA
- 1994-1998 BSc Biochemistry, University of Bath
Open to PhD supervision enquiries?
Yes
Current PhD students supervised
Katrina McCarten
Ute Koeber
Benjamin David Southgate
Karin Purshouse (Clinical PhD Student)
Research summary
Neural stem cells and brain cancer
Neural stem cells produce the neurons and glial cells that make up our nervous system. They can be expanded continuously in the laboratory, thereby providing an unlimited source of human cells for disease modelling and regenerative medicine.
Cells that have molecular hallmarks of neural stem cells drive human brain cancers, such as glioblastoma. A full understanding of the molecular and cellular events that control neural stem cell fate may therefore reveal new therapeutic strategies to treat this devastating disease.
We are exploiting the latest experimental tools of molecular and cellular biology to address the following questions: How do neural stem cells make the decision to make more copies of themselves (self-renew), or become specialised (differentiate)? Why do brain tumour stem cells display unconstrained self-renewal? Are those genes and pathways that initiate and maintain neural stem cell identity useful therapeutic targets for glioblastoma? Can we identify new drugs that can specifically block self-renewal of brain tumour stem cells?
Aims and areas of interest
The primary model system is a novel set of neural stem (NS) cell lines generated from rodent and human germinal tissues or from brain tumour biopsies. Genome editing, biochemical approaches and genome-wide profiling of transcription factor transcriptional targets are a current area of focus. These in vitro studies are complemented by in vivo assays (intracranial stereotaxic injection) and analysis of the developing mouse forebrain and primary tumour samples. We are also now exploring the zebrafish as a convenient model system to track neural stem cell behaviour in vivo.
There are currently four major areas of interest:
1. Lineage specific transcription factors.
We are using genetic and biochemical approaches to define the molecular mechanisms through which lineage-specific transcriptional regulators orchestrate self-renewal and differentiation, focussing on SOX, FOX and bHLH families. These lie at the heart of cell fate decision-making by neural stem and progenitor cells during development and within brain tumours.
2. Chemical and genetic screening
We are carrying out image-based small molecule screens to search for new agents and pathways that can modulate self-renewal and differentiation of normal and glioblastoma-derived neural stem cells.
3. Epigenetic programming and reprogramming
We are investigating whether changes to the epigenome within glioblastoma-derived cancer stem cells enable suppression of malignant properties. We are using both direct differentiation as well as nuclear reprogramming strategies to test this.
4. Genome editing
Designer transcription factors and nucleases (TALENs or CRISPR/Cas system) provide exciting new possibilities for sophisticated genetic and epigenetic manipulations of mouse and human neural stem cells. We are exploiting these tools with the goal of establishing efficient gene targetting in human neural stem cells and in directing stem cell fate.
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Glioblastoma stem cells induce quiescence in surrounding neural stem cells via Notch signalling.
In:
Genes and Development, vol. 34, pp. 1599-1604
DOI: https://doi.org/10.1101/gad.336917.120
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Reprogramming of Fibroblasts to Oligodendrocyte Progenitor-like Cells Using CRISPR/Cas9-Based Synthetic Transcription Factors
In:
Stem Cell Reports
DOI: https://doi.org/10.1016/j.stemcr.2019.10.010
Research output: Contribution to Journal › Article (Published) -
Post-translational modification of SOX family proteins: Key biochemical targets in cancer?
In:
seminars in cancer biology
DOI: https://doi.org/10.1016/j.semcancer.2019.09.009
Research output: Contribution to Journal › Review article (E-pub ahead of print) -
Experimental models and tools to tackle glioblastoma
In:
Disease Models and Mechanisms, vol. 12
DOI: https://doi.org/10.1242/dmm.040386
Research output: Contribution to Journal › Review article (E-pub ahead of print) -
The tumor suppressor CIC directly regulates MAPK pathway genes via histone deacetylation
In:
Cancer Research
DOI: https://doi.org/10.1158/0008-5472.CAN-18-0342
Research output: Contribution to Journal › Article (E-pub ahead of print) -
An efficient and scalable pipeline for epitope tagging in mammalian stem cells using Cas9 ribonucleoprotein
In:
eLIFE, vol. 7
DOI: https://doi.org/10.7554/eLife.35069
Research output: Contribution to Journal › Article (E-pub ahead of print) -
High expression of MKP1/DUSP1 counteracts glioma stem cell activity and mediates HDAC inhibitor response
In:
Oncogenesis, vol. 6, pp. 401
DOI: https://doi.org/10.1038/s41389-017-0003-9
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Modelling glioblastoma tumour-host cell interactions using adult brain organotypic slice co-culture
In:
Disease Models and Mechanisms
DOI: https://doi.org/10.1242/dmm.031435
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Pediatric brain tumor cells release exosomes with a miRNA repertoire that differs from exosomes secreted by normal cells
(12 pages)
In:
Oncotarget, vol. 8, pp. 90164-90175
DOI: https://doi.org/10.18632/oncotarget.21621
Research output: Contribution to Journal › Article (Published) -
The transcription factor Foxg1 promotes optic fissure closure in the mouse by suppressing Wnt8b in the nasal optic stalk
In:
Journal of Neuroscience
DOI: https://doi.org/10.1523/JNEUROSCI.0286-17.2017
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Oncogenic activity of SOX1 in glioblastoma
In:
Scientific Reports, vol. 7, pp. 46575
DOI: https://doi.org/10.1038/srep46575
Research output: Contribution to Journal › Article (E-pub ahead of print) -
EMMA: An Extensible Mammalian Modular Assembly Toolkit for the Rapid Design and Production of Diverse Expression Vectors
(13 pages)
In:
ACS Synthetic Biology, vol. 6, pp. 1380-1392
DOI: https://doi.org/10.1021/acssynbio.7b00016
Research output: Contribution to Journal › Article (Published) -
Elevated FOXG1 and SOX2 in glioblastoma enforces neural stem cell identity through transcriptional control of cell cycle and epigenetic regulators
(7 pages)
In:
Genes and Development, vol. 31, pp. 757-773
DOI: https://doi.org/10.1101/gad.293027.116
Research output: Contribution to Journal › Article (Published) -
Polymeric glabrescione B nanocapsules for passive targeting of Hedgehog-dependent tumor therapy in vitro
(18 pages)
In:
Nanomedicine, vol. 12, pp. 711-728
DOI: https://doi.org/10.2217/nnm-2016-0388
Research output: Contribution to Journal › Article (Published) -
Efficient CRISPR/Cas9-assisted gene targeting enables rapid and precise genetic manipulation of mammalian neural stem cells
In:
Development, pp. 635-648
DOI: https://doi.org/10.1242/dev.140855
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Proteome and Secretome Characterization of Glioblastoma-Derived Neural Stem Cells
In:
STEM CELLS
DOI: https://doi.org/10.1002/stem.2542
Research output: Contribution to Journal › Article (E-pub ahead of print) -
Quantitative stem cell biology: the threat and the glory
In:
Development, vol. 143
DOI: https://doi.org/10.1242/dev.140541
Research output: Contribution to Journal › Article (Published) -
Accelerating glioblastoma drug discovery: Convergence of patient-derived models, genome editing and phenotypic screening
In:
Molecular and Cellular Neuroscience
DOI: https://doi.org/10.1016/j.mcn.2016.11.001
Research output: Contribution to Journal › Article (E-pub ahead of print) -
STAR: a simple TAL effector assembly reaction using isothermal assembly
(9 pages)
In:
Scientific Reports, vol. 6
DOI: https://doi.org/10.1038/srep33209
Research output: Contribution to Journal › Article (E-pub ahead of print) -
EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells
In:
eLIFE, vol. 5
DOI: https://doi.org/10.7554/eLife.14845
Research output: Contribution to Journal › Article (Published)
More video
- Axel Behrens, CRUK LRI and Francis Crick Institute
- Stephan Beck, UCL Cancer Institute
- Paul Bertone, European Bioinformatics Institute and EMBL, Cambridge/Heidelberg
- Paul Brennan, University of Edinburgh and NHS Lothian
- Patrick Cai, SynthSys, University of Edinburgh
- Neil Carragher, University of Edinburgh
- Peter Dirks, Hospital for Sick Children, Toronto
- Robin Grant, NHS Lothian
- Jeroen Krijgsveld, European Molecular Biology Laboratory, Heidelberg
- John Mason, Centre for Integrative Physiology, University of Edinburgh
- Patrick Paddison, Fred Hutchison Cancer Centre, Seattle
- Dirk Sieger, Centre for Neuroregeneration, University of Edinburgh
- Bill Skarnes, Wellcome Trust Sanger Institute