BSc, MB, ChB (Bristol), PhD, FMedSci
My research is in novel approaches to cancer diagnosis. Improved understanding of cell biology is suggesting new ways to manage patients with cancer. Our group aims to identify genes of potential importance in the biology of malignancy, particularly cancer of the cervix and solid tumours of children. We are also testing the value of specific genes in diagnostic pathology, with the aim of improving screening for cancer and predicting how cancers will behave. Chromosome translocations are common in cancers of children. We have used high resolution molecular cytogenetic techniques to identify commonly occurring yet previously unrecognised chromosomal abnormalities. We are presently mapping selected translocation breakpoints, using a chromosome microdissection technique that incorporates fluorescent paints for easier identification of candidate translocations. We are also investigating mechanisms of progression of neoplasia in the cervix, with particular reference to integration of high-risk human papillomavirus into the host genome. In collaboration with Professor Margaret Stanley, we are undertaking detailed analysis of the cervical keratinocyte cell line W12, which serves as an excellent in vitro model of cervical neoplastic progression. Finally, we are testing the clinical value of markers such as the minichromosome maintenance (MCM) proteins, which are essential for DNA replication in eukaryotic cells. They are present throughout the cell cycle but are lost rapidly following differentiation and more slowly in quiescence. Antibodies against MCMs enable ready identification of malignant and pre-malignant cells in a variety of samples, including cervical smears, sputum and stool and are strong independent markers of outcome for patients with cancer.
Mechanisms of cervical neoplastic progression
1. Groves IJ and Coleman N (2015)
Invited review: Pathogenesis of human papillomavirus-associated mucosal disease.
The Journal of Pathology DOI: 10.1002/path.4496
2. Scarpini CG, Groves IJ, Pett MR, Ward D, Coleman N (2014)
Virus transcript levels and cell growth rates after naturally-occurring HPV16 integration events in basal cervical keratinocytes.
The Journal of Pathology 233:281-93
3. Hanning JE, Saini HK, Murray MJ, Caffarel MM, van Dongen S, Ward D, Barker EM, Scarpini CG, Groves IJ, Stanley MA, Enright AJ, Pett MR, Coleman N (2013)
Depletion of HPV16 early genes induces autophagy and senescence in a cervical carcinogenesis model, regardless of viral physical state.
The Journal of Pathology 231:354-66
4. Gray E, Pett MR, Ward D, Winder DM, Stanley MA, Roberts I, Scarpini CG, Coleman N (2010)
In vitro progression of human papillomavirus 16 episome-associated cervical neoplasia demonstrates fundamental similarities to integrant-associated carcinogenesis.
Cancer Research 70:4081-91
Therapeutic targets in squamous cell carcinoma
5. Caffarel MM, Coleman N (2014)
Invited perspective: Oncostatin M receptor is a novel therapeutic target in cervical squamous cell carcinoma.
The Journal of Pathology 232:386-90
6. Caffarel MM, Chattopadhyay A, Araujo AM, Bauer J, Scarpini CG, Coleman N (2013)
Tissue transglutaminase mediates the pro-malignant effects of oncostatin M receptor over-expression in cervical squamous cell carcinoma.
The Journal of Pathology 231:168-79
7. Winder DM, Muralidhar B, English W, Ng G, Roberts I, Murray MJ, Pett MR, Murphy G, Coleman N (2011)
Overexpression of the oncostatin M receptor in cervical squamous cell carcinoma cells is associated with a pro-angiogenic phenotype and increased cell motility and invasiveness.
The Journal of Pathology 225:448-62
8. Muralidhar B, Winder DM, Palmer RD, Barbosa-Morais NL, Ng G, Mukherjee G, Roberts I, Murray MJ, Pett MR, Coleman N (2011)
Functional evidence that Drosha over-expression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles.
The Journal of Pathology 224:496-507
Malignant germ cell tumours and paediatric cancers
9. Murray MJ, Raby KL, Saini HK, Bailey S, Wool SV, Tunnacliffe JM, Enright AJ, Nicholson JC, Coleman N
Solid tumors of childhood display specific serum microRNA profiles. (2015)
Cancer Epidemiol Biomarkers Prev cebp.0669.2014. [Epub ahead of print]
10. Murray MJ, Saini HK, Siegler CA, Hanning JE, Barker EM, van Dongen S, Ward DM, Raby KL, Groves IJ, Scarpini CG, Pett MR, Thornton CM, Enright AJ, Nicholson JC, Coleman N (2013)
LIN28 expression in malignant germ cell tumors downregulates let-7 and increases oncogene levels.
Cancer Research 73:4872-84
11. Murray MJ, Coleman N (2012)
Testicular cancer: a new generation of biomarkers for malignant germ cell tumours.
Nature Reviews Urology 9:298-300