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, 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.
-
Elevated FOXG1 in glioblastoma stem cells cooperates with Wnt/ß-catenin to induce exit 5 from quiescence.
In:
Cell Reports
DOI: https://doi.org/10.1016/j.celrep.2023.112561
Research output: Contribution to Journal › Article (Published) -
Oncogene expression from extrachromosomal DNA is driven by copy number amplification and does not require spatial clustering in glioblastoma stem cells
In:
eLIFE, vol. 11
DOI: https://doi.org/10.7554/eLife.80207
Research output: Contribution to Journal › Article (Published) -
Microglial secretome drives JAK-dependent Zika Virus resistance in Glioblastoma
In:
Neuron
Research output: Contribution to Journal › Article (Published) -
Simultaneous disruption of PRC2 and enhancer function underlies histone H3.3-K27M oncogenic activity in human hindbrain neural stem cells
(12 pages)
In:
Nature Genetics, vol. 53, pp. 1221-1232
DOI: https://doi.org/10.1038/s41588-021-00897-w
Research output: Contribution to Journal › Article (Published) -
Hierarchical reactivation of transcription during mitosis-to-G1 transition by Brn2 and Ascl1 in neural stem cells
(15 pages)
In:
Genes and Development, vol. 35, pp. 1020-1034
DOI: https://doi.org/10.1101/gad.348174.120
Research output: Contribution to Journal › Article (Published) -
Neural G0: a quiescent-like state found in neuroepithelial-derived cells and glioma
(29 pages)
In:
Molecular Systems Biology, vol. 17
DOI: https://doi.org/10.15252/msb.20209522
Research output: Contribution to Journal › Article (Published) -
LRIG1 is a gatekeeper to exit from quiescence in adult neural stem cells
In:
Nature Communications
DOI: https://doi.org/10.1038/s41467-021-22813-w
Research output: Contribution to Journal › Article (Published) -
Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion
In:
Cell
DOI: https://doi.org/10.1016/j.cell.2021.03.023
Research output: Contribution to Journal › Article (Published) -
The white matter is a pro-differentiative niche for glioblastoma
In:
Nature Communications, vol. 12, pp. 2184
DOI: https://doi.org/10.1038/s41467-021-22225-w
Research output: Contribution to Journal › Article (Published) -
Regional identity of human neural stem cells determines oncogenic responses to histone H3.3 mutants
(27 pages)
In:
Cell Stem Cell, vol. 28, pp. 877-893.e9
DOI: https://doi.org/10.1016/j.stem.2021.01.016
Research output: Contribution to Journal › Article (Published) -
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) -
Selective toxicity of functionalised graphene oxide to patients-derived glioblastoma stem cells and minimal toxicity to non-cancerous brain tissue cells
In:
2D Materials, vol. 7, pp. 045002
DOI: https://doi.org/10.1088/2053-1583/ab9a0f
Research output: Contribution to Journal › Article (Published) -
Transcriptional and epigenetic regulatory mechanisms in glioblastoma stem cells
DOI: https://doi.org/10.1016/B978-0-12-814085-7.00010-6
Research output: › Chapter (Published) -
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) -
Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis
In:
Cell Stem Cell, vol. 25, pp. 433-446.e7
DOI: https://doi.org/10.1016/j.stem.2019.05.013
Research output: Contribution to Journal › Article (Published) -
Challenges to curing primary brain tumours
(12 pages)
In:
Nature Reviews Clinical Oncology, vol. 16, pp. 509-520
DOI: https://doi.org/10.1038/s41571-019-0177-5
Research output: Contribution to Journal › Review article (Published) -
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)
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