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- Reader in Developmental Neurobiology
- ICH Development Bio & Cancer Prog
- UCL GOS Institute of Child Health
- Faculty of Pop Health Sciences
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)
1986 to 1988 EMBO Research Fellow
1988 to 1991 University of California Postdoctoral Scientist
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 Reader, Institute of Child Health, University College London
Since 2000 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.
Since 20012 I have been the Departmental Graduate Tutor in the Institute of Child Health and since 2013 I have been the FPHS Faculty Graduate Tutor (res). I remain heavily involved in matters of postgraduate research student management and development.
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, we have also investigated the transcriptional basis of oxovanadium’s enhancement of retinoid actions and now have a cohort of candidate genes that are being studied as potential effectors of the retinoid/oxovanadium combination. Similar studies will soon be carried out to understand the basis of the synergistic toxicity generated by oxovanadium and glutathione blockers.
Lastly, we have recently begun work on technical aspect of drug delivery in neuroblastoma. Since retinoids and oxovanadium both have associated problems with pharmacokinetics and delivery, we have initiated studies in nanotechnology to develop nanocarriers for these chemicals. The aim will be to improve drug efficacy and reduce toxicity in children.
My direct teaching roles are:
1) Lecturing on cell signalling on the MRes in Biomedicine at ICH
2) Direct research training of PhD and MRes students in my laboratory
3) Lecturing on peripheral nervous system development under the MSc/MRes Neuromuscular Disease
4) Lecturing on paediatric neuroblastoma under the MSc Paediatrics and Child Health
5) Extended tutorial on the tyrosine phosphatase enzyme family, for MRC programme funded PhD students at the UCL LMCB.
6) a range of workshops for PhD students under the Doctoral School Skills Programme
|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|
|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|