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1991 - | Professor of Molecular Biology, Director YCR Cancer Research Unit | Department of Biology, University of York |
1989 - 1991 | Senior Lecturer in Molecular Pathology | Department of Pathology, University of Bristol |
1983 - 1989 | New Blood Lecturer in Molecular Pathology | Department of Pathology, University of Bristol |
1977 - 1983 | Cancer Research Campaign Research Fellow | Department of Genetics, University of Edinburgh |
1976 - 1977 | Robertson Research Fellow | Cold Spring Harbor Laboratory, New York |
1974 - 1977 | PhD in Cancer Studies | University of Birmingham |
1970 - 1974 | BSc Biochemistry (First Class Hons) | University of Glasgow |
My research in the YCR Cancer Research Unit is now focused on the development and aetiology of human prostate cancer. Our overall approach has been to separate the tumour (and the corresponding normal tissue) into its cellular components, and to study the role played by different cell types. Of particular interest are the roles played by epithelial stem cells and the hormone-sensitive stromal cells within the tumour and normal prostate. We have compiled gene expression profiles for the various cell types using the Affymetrix platform, and have mined this data for genes and signalling pathways which affect cell fate. Much of our research is now concerned with hypothesis testing, based on the identified genes from this study, using complex multicellular models in vitro and developing xenograft models of the tumour. Clearly fate-altering genes also have therapeutic significance, and in a spin out company (Pro-Cure Therapeutics, founded in 2001) an associated research team are developing novel cancer stem cell treatments, based on the output of the YCR Research. There is a close collaboration between the two groups. As part of an International collaboration, coordinated from York, we are also developing novel biotherapies for prostate cancer, based on targeted and stealthed viral vectors, which allow us to either focus gene expression in specific cells within a tumour, or to engineer viruses to replicate only in tumour cells (oncolytics).
Discoveries
We have shown that heterogeneity within human prostate cancers is due to both carcinogenic changes but also aberrant differentiation, which are two independent events. Current therapies are directed against the majority of cells in the tumour (the most differentiated cells) but do not affect the minority population, which are the tumour initiating cells or cancer stem cells. Thus these cells form a root for post therapy recurrence. By exploiting our gene expression profiling of these cells we have designed potentially novel treatments, which could delay or even prevent tumour recurrence. However we have also shown that the cancer stem cells have an active resistance mechanism to many therapies, such as radiotherapy and chemotherapy. By exploiting a novel ex vivo human blood loop system we have shown that a powerful complement response can eliminate the therapeutic doses of gene therapy vectors, and that co-inoculation with 2 complement inhibitors can block this effect (not seen in mouse models).
Status | Name | Project |
---|---|---|
Postdoctoral Research Associate | Dr Anne Collins | Near-patient prostate cancer models for the assessment of disease, prognosis and therapy response |
Postdoctoral Research Associate | Dr Fiona Frame | Prediction of patient tumour responses to radiotherapy or current and novel chemotherapies by treatment |
Postdoctoral Research Associate | Dr Amanda Noble | Prediction of patient tumour responses to radiotherapy or current and novel chemotherapies by treatment |
Honorary Fellow (retired SL) | Dr Martin Rumsby | Role of lipid metabolism in prostate cancers |
Postdoctoral Research Associate | Dr Dominika Butler | Appraisal of Anisina combination therapy with docetaxel using human prostate cancer cells maintained |
Postdoctoral Research Associate | Dr Rob Seed | Functional analysis of the role of the Stem Cell Control Gene Latexin in prostate cancer invasion |
Postdoctoral Research Associate | Dr Holger Erb | Can we exploit microRNA express patterns to improve the prognosis for prostate cancer patients? |
Senior Research Technician | Hannah Walker | Prediction of patient tumour responses to radiotherapy or current and novel chemotherapies by treatment |
PhD Student | Adam Hirst | Effects of low temperature plasma on prostate cancer cells (with York Plasma Institute) |
PhD Student | Alberto Taurozzi | Effects of low temperature plasma on prostate cancer cells (with York Plasma Institute) |
PhD Student | John Packer | Monoallelic expression of genes in prostate cancer |
PhD Student | Leanne Archer | The role of ELF3 in prostate cancer epithelial differentiation |
Visiting PhD student | Giovanna Nappo | Effects of stromal IL4 on prostate cancer stem cells |
Visiting PhD student | Susana del Rocio Solrzano Rosales | Telomere length in purified subpopulations of cells from prostate cancers |
Collins AT, Maitland NJ. (2009)
Prostate cancer: Regeneration of interest in the prostate.
Nat Rev Urol. Apr:6 (4) 184-6
Swift, S, Maitland N.J, (2010)
Altered Expression of Neurotensin Receptor is Associated with the Differentiation State of Prostate Cancer Cancer Research 70: 347-356
Burns JE, Walker HF, Schmitz C, Maitland NJ. (2010)
Phenotypic effects of HPV16 E2 protein expression in human keratinocytes
Virology. Jun 5;401(2):314-21
Frame FM, Hager S, Pellacani D, Stower MJ, Walker HF, Burns JE, Collins AT, Maitland NJ. Development and limitations of lentivirus vectors as tools for tracking differentiation in prostate epithelial cells. Exp Cell Res. 2010, 316 (19): 3161-71
Muthana, M., Maitland N.J., Giannoudis A., Scott S.D., Fang H.Y., Coffelt S.B., Morrow F.J., Murdoch C., Burton J.L., Cross N., Burke B., Mistry R., Hamdy F., Brown N.J., Georgopolous L., Hoskin P.J., Essand M., and Lewis C.E. (2011) Use of Macrophages to target therapeutic adenovirus to human prostate tumours. Cancer Res. 71(5):1805-1815
Maitland N.J., Magnusson M.K., Kraaj R., Leadley R.M., de Ridder C.M.A., van Weerden W.M. Hoeben R.C. and Lindholm L. A transductionally re-targeted adenovirus vector for virotherapy of Her2/neu expressing prostate cancer. Human Gene Therapy 21 (7): 815-27