UCL Cancer Institute

Neural Stem Cells and Brain Cancer


Group Leader: Dr Steven Pollard




Our group focuses on the most common and malignant form of primary adult brain cancer, known as glioblastoma multiforme. These tumours are made up of several phenotypically distinct cell types, including an immature stem cell population which is thought to drive tumour growth.

'The Pollard laboratory will be relocating from UCL to the MRC Centre for Regenerative Medicine (University of Edinburgh) in October 2013'.

Please find our new webpage here.


Research

The long term goal of our research is to uncover the molecular and cellular mechanisms that control stem cell lineage choice, commitment and differentiation.

Our specific focus is on mammalian neural stem cells and we are studying how these pathways operate in the context of the lethal human brain cancer, glioblastoma. 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. These in vitro studies are complemented by in vivo assays (stereotaxic injection) and analysis of the developing mouse forebrain and primary tumour samples.

There are currently three major areas of interest:

1. Lineage specific transcription factors. We are investigating the function and biochemistry of lineage specific transcriptional regulators, such as members of the SOX, FOX and bHLH family. These lie at the heart of cell fate decisions in neural stem and progenitor cells during development and within brain tumours. (Dr Christine Ender and Bart Baranowski)

2. High content chemical screening We are carrying out image-based small molecule screens to search for new agents and pathways that can modulate self-renewal and differentiation in normal and glioblastoma-derived neural stem cells. (Dr Davide Danovi and Bart Baranowski)

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. (Dr Stefan Stricker, Mr Julio Granados-Montiel and Dr Helena Caren)

Our hope is that these studies will uncover new possibilities for targeted therapy for glioblastoma.

Chemical screens spacer


Chemical screens have been used to identify a small molecule with cancer specific effects. Upon treatment glioblastoma cells are blocked at prometaphase and have a striking spindle defect. Spindle is stained blue (alpha tubulin) and mitotic chromsomes are stained green (pHH3).

 


Undifferentiated cancer stem cells

neural stem cells

Glioblastoma-derived neural stem cells undergoing differentiation. Cells co-expressing Olig2 (green) and Sox10 (red) begin to differentiate to the oligodendrocyte lineage (O4, white).



 

Brief CV Dr Steven Pollard

  • 2010–current: Group Leader, Samantha Dickson Brain Cancer Unit and UCL Cancer Institute
  • 2006–2009: Beit Research Fellow and Kaye Fellow (Christ’s College) with Austin Smith, Centre for Stem Cell Research, University of Cambridge
  • 2002-2006: Postdoc with Austin Smith, Institute for Stem Cell Research, University of Edinburgh
  • 1998–2002: PhD student with Derek Stemple, MRC National Institute for Medical Research, Mill Hill, London
  • 1994-1998: BSc Biochemistry, University of Bath

Selected Publications


1. Imaging-based chemical screens using normal and glioma-derived neural stem cells. Danovi D, Falk A, Humphreys P, Vickers R, Tinsley J, Smith AG, Pollard SM. Biochem Soc Trans. 2010 Aug;38(4):1067-71. Pubmed

2. Pollard SM, Stricker SH, Beck S. Preview. A shore sign of reprogramming. (Preview article) Cell Stem Cell. 2009 Dec 4;5(6):571-2. Pubmed

3. Pollard SM¹ ², Yoshikawa K¹, Clarke I, Danovi D, Stricker S, Russell R, Bayani J, Head R, Lee M, Bernstein M, Squire J, Smith A and Dirks P². Glioma stem cell lines expanded in adherent culture have tumour-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell 2009 Jun 5;4(6):568-80. Pubmed

4. Pollard SM², Wallbank R, Tomlinson S, Grotewold L, and Smith A². FGF induces a neural stem cell phenotype in foetal forebrain progenitors and during embryonic stem cell differentiation. Mol Cell Neurosci. 2008 Jul;38(3):393-403. Epub 2008 Apr 10. Pubmed

5. Conti L¹, Pollard SM¹, Gorba T, Reitano E, Toselli M, Biella G, Sun Y, Sanzone S, Ying QL, Cattaneo E, Smith A. Niche-independent symmetrical self-renewal of a mammalian tissue stem cell. PLoS Biol. 2005 Sep;3(9):e283. Pubmed

( ¹ Contributed Equally; ² Joint Corresponding Author)

Full publication list at Researcher ID

 

 

Steven Pollard

Dr Steven Pollard


Group Members

  • Bart Baranowski (PhD student)
  • Dr Helena Caren (Postdoc, Shared with Prof Stephan Beck)
  • Dr Davide Danovi
  • Dr Christine Ender (Marie Curie Fellow)
  • Dr Sladjana Gagrica (Research Assistant)
  • Dr Stefan Stricker (EMBO Fellow)
  • Julio Granados-Montiel (PhD Student, UCL Grand Challenges)

 



 

Collaborators


  • Stephan Beck (UCL Cancer Institute)
  • Paul Bertone (European Bioinformatics Institute and EMBL, Cambridge/Heidelberg)
  • Sebastian Brandner (Institute of Neurology, Queen Square)
  • Peter Dirks (Hospital for Sick Children, Toronto)
  • Amos Folarin (Computational Biology, UCL Cancer Institute)
  • Robin Ketteler (MRC Laboratory of Molecular and Cellular Biology)
  • Jeroen Krijsveld (European Molecular Biology Laboratory, Heidelberg)
  • Patrick Paddison (Fred Hutchison Cancer Centre, Seattle)
  • Austin Smith (University of Cambridge)
  • Bill Richardson (WIBR, UCL)