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Dr Andrew Stoker
Institute of Child Health UCL
30 Guildford Street
London
WC1N 1EH
Appointment
  • Reader in Developmental Neurobiology
  • ICH Development Bio & Cancer Prog
  • UCL GOS Institute of Child Health
  • Faculty of Pop Health Sciences
Biography

Education

1979-1982 :        University of Cambridge, England.
            Natural Sciences Tripos; Part II Genetics.
            Part II Supervisor : Dr. Martin Evans
            Awarded :  BA in Natural Sciences  (Class II.I)
            Awarded :  MA in 1985.

1982-1986 :        Imperial Cancer Research Fund, London.
            Supervisor : Dr. John A. Wyke.
            Awarded : Ph.D. April 1986 (UCL, University of London)


Professional History
    
    
1986 to 1988        EMBO Research Fellow
1988 to 1991        University of California Postdoctoral Scientist
Positions
held at:                  Division of Cell and Molecular Biology,
                              Lawrence Berkeley Laboratory,
                              Berkeley, CA, USA.
                             Supervisor: Dr. Mina J. Bissell

Oct 1991 to          Royal Society University Research Fellow,     
May 1998            Department of Human Anatomy, University of Oxford

June 1998 to         Royal Society University Research Fellow & University Lecturer,
Sept 1999              Institute of Child Health, University College London

October 1999         Senior Lecturer, Institute of Child Health, University College
to present                London

October 2002    Associate Professor, Institute of Child Health, University College London
To present


I have coordinated two Research Training Networks under EC Frameworks FP5 and FP6. These focused on the function of PTP enzymes in a range of disease models and were successful in training nearly 20 PhD students and postdocs.

From 2012-2017 I was the Departmental Graduate Tutor in the Institute of Child Health and since 2015 I have been the FPHS Faculty Graduate Tutor (research). I am integrally involved in matters of UCL postgraduate research student training, management and support.


Research Summary

My research group has historically focussed on understanding on phosphotyrosine signalling in axonogenesis and neurogenesis, with particular interest in understanding the roles of the tyrosine-specific phosphatases (PTPs). More recently we have begun to apply our knowledge to nervous system cancers, focusing on oxovanadium compounds (PTP inhibitors), in combinations with retinoids or glutathione suppressors, as potential therapeutic platforms in neuroblastoma, a sympathoadrenal tumour of children.
    PTP enzymes are highly expressed in developing neural tissues. I was the first to demonstrate  PTPsigma enrichment in embryonic sensory and retinal axons and that receptor PTPs (RPTPs) localise to growth cones and control retinotectal axon targeting. We also demonstrated roles of PTPgamma and PTPsigma in spinal motor neuron development in the chick embryo model. Moreover, our extensive work on RPTP ligands in collaboration with Radu Aricescu has demonstrated that PTPsigma has heparan sulphate proteoglycans (HSPGs) as ligands and that this has relevance to both nerve regeneration and synaptogenesis. We have generated insights into the molecular regulation of neural RPTPs, defining the complex co-expression patterns of RPTP expression with neurotrophin receptors (the TRK family) in primary DRG neurons and showing direct interactions of PTPsigma with TRKs. This regulation of TRK signals by PTPs is relevant to our current research on cancer, since TRK expression correlates with prognosis in neuroblastoma.
    Currently the laboratory is using its experience in PTP enzymes and developmental neurobiology to focus on basic and translational aspects of the molecular and cellular biology of neuroblastoma. We have shown that PTP inhibitors of the oxovanadium family can enhance retinoids actions in inducing differentiation and senescence in tumour-derived cell lines. Further, novel studies showed that oxovanadium synergises strongly with inhibitors of glutathione synthesis to induce high levels of cytotoxicity in most neuroblastoma cell lines. Both of these areas are of interest in the longer term for potentially enhancing residual disease treatment in patients. Our objectives have included the identification of PTP protein family members that may be acting as “survival-promoters” in these tumours cells. Using an shRNA knockdown screen, we have identified candidate enzymes that we are now following up as potential drug targets. Using RNAseq approaches, we have also investigated the transcriptional basis of oxovanadium’s interactions with retinoids and glutathione blockers and have identifed a novel group of candidate genes that promote the proliferation and survival of neuroblastoma cells. These are being investigated to improve our understanding of growth control in these tumour cells, and also as potential leads for future theraputic approaches.

Lastly, we have recently worked with collaborators in Cardiff on the beneficial effects of CYP26 inhibitors as enhancers of retinoid action in neuroblastoma cells. We have shown for the first time that such inhibitors can enhance retinoic acid's ability to induce cell differentiation and suppress growth. Since delivery to tissues is hindered by high hydrophobilicty of the inhibitors, we have also worked to demonstrate efficient delivery to cells using liposomal nanotechnology. We now want to understand whether such an approach may improve retinoid action during neuroblastoma treatment in vivo.

Teaching Summary

My direct teaching roles are:

1) Lecturing on cell signalling on the MRes in Biomedicine at ICH

2) Lecturing on peripheral nervous system development under the MSc/MRes Neuromuscular Disease and MSc CLINICAL NEUROSCIENCE/NEUROLOGY

3)  Lecturing on paediatric neuroblastoma under the MSc Paediatrics and Child Health

4) Research project supervision of BSc, MSc and PhD students in my laboratory

5) Module lead for the URCA Module in the Cell and Gene Therapy MSc at GOSICH


6) External examiner for the MSc in Cancer Biology, University of Kent

7) I am Faculty Graduate Tutor for research in Population Health Sciences and this includes running skills workshops for PhD students

Appointments
01-APR-2012 Departmental Graduate Tutor (Research) Institute of Child Health UCL, United Kingdom
01-OCT-2002 Reader Institute of Child Health UCL, United Kingdom
Academic Background
1986 PhD Doctor of Philosophy – Genetics and Biochemistry University College London
1985 MA Master of Arts University of Cambridge
1982 BA Bachelor of Arts – Natural Sciences University of Cambridge
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