Professor E Kenneth Parkinson, BSc, PhD

Head of Research for Clinical and Diagnostic Sciences, Head of the Oral Cancer Research Group within the Institute of Dentistry.

Contact details

Professor Parkinson was born in Blackpool Lancashire in 1952 and was educated at Blackpool Grammar School before obtaining his BSc. at Queen Elizabeth College (later part of King’s College), the University of London in 1974.  After obtaining his PhD from the University of Glasgow in 1977, he was a postdoctoral fellow at the CR UK Institute for Cancer Studies in Birmingham where in 1982 he developed the hypothesis that an important component of tumour promotion involved the selective killing of normal keratinocytes thus allowing the aberrant initiated cells to clonally expand.  He moved briefly to the Paterson Institute in Manchester, before becoming a Senior Research Group Leader at the Beatson Institute for Cancer Research, Glasgow until January 2005. Whilst there his research group provided the first evidence that deletion of the INK4A locus was linked to cancer cell immortality and later showed that the most important gene was p16INK4A, which accumulated when skin epithelial cells age in culture a result recently extended to ageing human skin in vivo.  His group also combined with Nicol Keith’s to provide the first evidence that a human telomerase gene was an oncogene, an interpretation recently confirmed by the presence of the same gene in the genome of a chicken lymphoma virus. More recent collaborations with Professor Paul Harrison’s group in Glasgow have suggested that oral squamous cell carcinomas may progress by two distinct routes, only one of which leads to the cells becoming immortal (recently reviewed in Hunter et al Nature Reviews in Cancer).  This work may be important in the future in the classification and treatment of oral cancer.

Publications:

Key Publications

Edington KG, Loughran OP, Berry IJ and Parkinson EK. Cellular immortality: A late event in the progression of human squamous cell carcinoma of the head and neck associated with p53 alteration and a high frequency of allele loss.  Mol. Carcinog. (1995) 13: 254-265.

Loughran O, Malliri A, Owens D, Gallimore PH, Stanley MA, Ozanne B, Frame MC and Parkinson EK.  Association of CDKN2A/p16INK4A with human head and neck keratinocyte replicative senesence: relationship of the dysfunction to immortality and neoplasia.  Oncogene (1996), 13: 561-568.

Loughran O, Clark, LJ, Bond J, Baker A, Berry IJ, Edington KG, Ly I-S, Simmons R, Haw R, Black DM, Newbold RF and Parkinson EK.  Evidence for the inactivation of multiple replicative lifespan genes in immortal human squamous cell carcinoma keratinocytes.  Oncogene (1997), 14: 1955-1964.

Soder AI, Hoare SE, Muire S, Going JJ, Parkinson EK and Keith WN.  Amplification and increased gene dosage of the telomerase RNA gene in human cancer.  Oncogene (1997) 14: 1013-1021.

Munro J, Stott FJ, Vousden KH, Peters G and Parkinson EK.  The role of the alternative INK4A proteins in human keratinocyte senescence : Evidence for the specific inactivation of p16INK4A upon immortalization.  Cancer Res. (1999) 59: 2516-2521.

McCaul J, Gordon K, Clark LJ and Parkinson EK. Telomerase inhibition and the future management of head-and-neck cancer.  Lancet Oncology (2002) 3: 280-288.

Gordon KE, Ireland H, Roberts M, Steeghs K, McCaul JA, McDonald DG and Parkinson EK.  High levels of telomere dysfunction bestow a selective disadvantage during the progression of oral squamous cell carcinoma. Cancer Res. (2003) 63: 458-67.

Hunter K, Parkinson EK and Harrison PR.  Profiling early head and neck cancer. Nature Reviews in Cancer (2005) 5: 127-135.

Hunter KD, Thurlow JK, Fleming J,  Drake PJH, Vass JK, Kalna G, Higham DJ, Herzyk, P, MacDonald DG, Parkinson EK and Harrison PR. Divergent routes to oral cancer. Cancer Res. (2006) 66: 7405-7413.

McCaul, JA, Gordon KE, Minty F, Fleming J and Parkinson EK. Telomere dysfunction is related to the intrinsic radio-resistance of human oral cancer cells. Oral Oncology (2007) 44: 261-269.

Publications since 2001

Munro J, Steeghs K, Morrison V, Ireland H. and Parkinson EK.  Human fibroblast replicative senescence can occur in the absence of extensive cell division and short telomeres.Oncogene. (2001) 20 : 3541-52.

Snaddon J, Parkinson EK, Craft JA, Bartholomew C and Fulton R.  Detection of functional PTEN lipid phosphatase protein and enzyme activity in squamous cell carcinomas of the head and neck, despite loss of heterozygosity at this locus. Br J Cancer. (2001) 84:1630-1634.

Paterson IC, Davies M, Stone A, Huntley S, Smith E, Pring M, Eveson JW, Robinson CM, Parkinson EK and Prime SS. TGF-beta1 acts as a tumor suppressor of human malignant keratinocytes independently of Smad 4 expression and ligand-induced G(1) arrest. Oncogene. (2002) 21: 1616-24.

McGregor F, Muntoni A, Fleming J, Brown J, Felix DH, MacDonald DG, Parkinson EK and Harrison PR.  Molecular changes associated with oral dysplasia progression and acquisition of immortality: potential for its reversal by 5-azacytidine. Cancer Res. (2002) 62: 4757-66.

Forsyth NR, Morrison V, Craig NJ, Fitzsimmons SA, Barr NI, Ireland H, Gordon KE,  Dowen S, Cuthbert AP, Newbold RF, Bryce SD and Parkinson EK. Functional evidence for a squamous cell carcinoma mortality gene(s) on human chromosome 4. Oncogene. (2002) 21: 5135-47.

Bryce SD, Morrison V, Craig NJ, Forsyth NR, Fitzsimmons SA, Ireland H, Cuthbert AP, Newbold RF and Parkinson EK. A Mortality Gene(s) for the Human Adenocarcinoma Line HeLa Maps to a 130-kb Region of Human Chromosome 4q22-q23. Neoplasia. (2002) 4: 544-50.

Toomes, C, Jackson, AP, MacGuire, K, Wood, AJ, Gollin, SM, Ishwad, CS, Paterson, IC, Prime, SS, Parkinson, EK, Bell SM, Woods, CG, Markham, AF, Oliver, R, Woodward, R, Sloan, P, Dixon, MJ, Read, AP and Thakker, N. Multiple regions of homozygous deletion at the CSMD 1 locus in oral squamous cell carcinoma: a new suppressor gene? Genes Chromosomes and Cancer (2003) 37: 132-140.

Fitzsimmons, SA, Ireland, H, Barr, NI, Cuthbert, A, Going, JJ, Newbold RF and Parkinson EK. Human squamous cell carcinomas lose a mortality gene from chromosome 6q14.3-q15. Oncogene (2003) 22:1737-1746.

Gordon KE, Ireland H, Roberts M, Steeghs K, McCaul JA, McDonald DG, Parkinson EK.  High levels of telomere dysfunction bestow a selective disadvantage during the progression of oral squamous cell carcinoma. Cancer Res. (2003) 63: 458-67.

Wootton M, Steeghs K,  Watt D, Munro J, Gordon K, Ireland H, Morrison V, Behan W, Parkinson EK.  Telomerase alone extends the replicative lifespan of human skeletal muscle cells without compromising genomic stability.  Human Gene Therapy (2003) 14: 1473-1487.

Muntoni A, Fleming J, Gordon KE, Hunter K, McGregor F, Parkinson EK, Harrison PR. Senescing  oral dysplasias are not immortalized by ectopic expression of hTERT alone without other molecular changes, such as loss of INK4A and/or retinoic acid receptor-beta: but p53 mutations are not necessarily required.  Oncogene (2003) 22: 7804-7808.

Munro J, Barr NI, Ireland H, Morrison V, Parkinson EK. Histone deacetylase inhibitors induce a senescence-like state in human cells by a p16-dependent mechanism that is independent of a mitotic clock. Exp Cell Res. (2004) 295: 25-38.

Scott LA, Vass K, Parkinson EK Gillespie DA, Winnie JN and Ozanne B. Invasion of normal human fibroblasts induced by v-Fos is independent of proliferation, immortalization and the tumor suppressors p16INK4A and p53. Mol. Cell Biol. (2004) 24: 1540-1559.

Hewitt, CA, Wilson, P, McGlinn, E, MacFarlane, G, Papageorgiou, A, Woodwards, R, Sloan, P, Gollin, S, Paterson, IC, Parkinson, EK, Read, AP and Thakker, N. Frequent allelic imbalance at DLC-1 locus but a lack of mutations or loss of expression of DLC-1 in oral squamous cell carcinoma. Cancer Lett. (2004) 209: 207-213.

Sedghizadeh PP, Mallery SR, Thompson SJ, Kresty L, Beck FM, Parkinson EK, Biancamano J and Lang JC.  Expression of the serine protease DESC1 correlates directly with normal keratinocyte differentiation and inversely with head and neck squamous cell carcinoma progression. Head and Neck (2006) 28:432-40.

Pring M, Prime S, Parkinson EK and Paterson I. Dysregulated TGF-beta1-induced Smad signalling occurs as a result of defects in multiple components of the TGF-beta signalling pathway in human head and neck carcinoma cell lines. Int J Oncol. (2006) 28:1279-85.

Hunter KD, Thurlow JK, Fleming J,  Drake PJH, Vass JK, Kalna G, Higham DJ, Herzyk, P, MacDonald DG, Parkinson EK and Harrison PR. Divergent routes to oral cancer. Cancer Res. (2006) 66: 7405-7413.

McCaul, J.A., Gordon, K.E.,  Minty, F., Fleming, J. and Parkinson E.K. Telomere dysfunction is related to the intrinsic radio-resistance of human oral cancer cells. Oral Oncology (2008) 44:261-269.

Lalli, A.,  Tilakaratne, W.M., Ariyawardena, A., Fitchett, C.,  Leigh, I.M., Hagi-Pavli, E., Cruchley, A.T., Parkinson, E.K., Teh, M-T., Fortune, F. and Waseem, A. An altered keratinocyte phenotype in oral submucous fibrosis: correlation of keratin K17  expression with disease severity. J.Oral Pathol.Med. (2008) 37 : 211-220.

Tilakaratne, W.M., Iqbal, Z., The, M.T., Ariyawardana, A., Pitiyage, G., Cruchley, A., Stewart, J.E., Hagi-Pavli, E., Lalli, A., Waseem, A., Parkinson, E.K. and Fortune, F. Upregulation of HIF-1alpha in malignant transformation of oral submucous fibrosis. J. Oral. Pathol. Med. (2008) 37: 372-7.

Minty, F., Thurlow, J., Harrison, P.R., Parkinson, E.K.Telomere dysfunction in human keratinocytes elicits senescence and a novel transcription profile. Exp. Cell Res. (2008) 314: 2434-47.

MacIntyre, A., Brouilette, S.W., Lamb, K., Radhakrishnan. K., McGlynn, L., Chee, M.M., Parkinson, E.K., Freeman, D., Madhok, R., Shiels, P.G.Association of increased telomere lengths in limited scleroderma, with a lack of age-related telomere erosion.  Ann Rheum Dis. (2008) 67: 1780-2.

Syed, M.I., Syed, S., Minty, F., Harrower, S., Singh, J., Chin, A., McClellan, D.R., Parkinson, E.K., Clark, L.J. Gamma tubulin: A promising indicator of recurrence in squamous cell carcinoma of the larynx. Otolaryngol. Head & Neck Surgery (2009) 140: 498-504.

Gemenetzidis, E. Bose, A., Riaz, A.M., Chaplin, T., Young, B.D., Ali, M., Sugden,D., Thurlow, J.K.,  Cheong, S.C., Teo, S-H., Wan, H., Waseem, A., Parkinson, E.K., Fortune, F., Teh, M.T..Upregulation of FOXM1 is an Early Event in Human Squamous Cell Carcinoma and Co-operates with Nicotine in Malignant Transformation PLoS ONE (2009) 4: e4849.

Thurlow, J.K., Peña Murillo, C.L., Hunter, K.D., Buffa, F.M. Patiar, S., Betts,G., West, C.M.L., Harris, A.L., Parkinson, E.K., Harrison, P.R., Ozanne, B.W., Partridge, M. and Kalna, G. Spectral clustering of microarray data elucidates the roles of microenvironment remodelling and immune responses in survival of head and neck squamous cell carcinoma. J. Clin.Oncol. (2010) 28:2881-8.

Teh, M.T., Parkinson, E.K., Thurlow, J.K., Liu, F., Fortune, F., Wan, H. Molecular signature of desmosomal proteins in head and neck squamous cell carcinoma. J. Oral. Pathol. Med. (2010) Oct 4. doi: 10.1111/j.1600-0714.2010.00951.x. [Epub ahead of print].

Gemenetzidis, E., Elena-Costea, D., Parkinson, E.K. Waseem A., Wan, H. and Teh, M.T. Induction of Human Epithelial Stem/Progenitor Expansion by FOXM1. Cancer Res. (2010) Nov 9. [Epub ahead of print].

Pitiyage G.N., Slijepcevic P., Gabrani A., Chianea Y.G., Lim K.P., Prime S.S., Tilakaratne W.M., Fortune F., Parkinson E.K. Senescent mesenchymal cells accumulate in oral fibrosis prior to epithelial neoplasia due to the intrinsic generation of reactive oxygen species. (2010) J.Pathol. In Press.

Lim, K.P., Cirillo, N., Hassona, Y., Wei W., Thurlow, J.K., Cheong, S.C., Pitiyage, G. Parkinson, E.K. and Prime, S.S. Fibroblast gene expression profile reflects the stage of tumor progression in oral squamous cell carcinoma. (2010) J.Pathol. In Press.

Review Articles

McCaul J, Gordon K, Clark LJ and Parkinson EK. Telomerase inhibition and the future management of head-and-neck cancer.  Lancet Oncology (2002) 3: 280-288.

Parkinson E.K.  Telomerase as a novel and potentially selective target for cancer chemotherapy. Annals of Medicine (2003) 35: 466-475.

Hunter K, Parkinson EK and Harrison PR.  Profiling early head and neck cancer. Nature Reviews in Cancer (2005) 5: 127-135.

Parkinson, E.K.  Telomerase as a target for cancer therapy.  Current Opinion in Investigational Drugs (2005) 6: 605-610.

Parkinson, E.K. and Minty, F. Anticancer therapy: Targeting telomeres and telomerase. Biodrugs (2007) 21: 375-85.

Parkinson, E.K., Fitchett, C.J. and Cereser, B. Dissecting the non-canonical functions of telomerase. Cytogenetics & Genome Research (2008) 122: 273-280.

Parkinson, E.K. Senescence as a modulator of oral squamous cell carcinoma development. Oral Oncology (2009) In Press.

Parkinson, E.K. Senescence as a modulator of oral squamous cell carcinoma development. Oral Oncology (2010) Nov 1. [Epub ahead of print].

Book Chapters

Edington, K.G., Berry, I.J., O'Prey, M., Burns, J.E., Clark, L.J., Mitchell, R., Robertson, G., Soutar, D., Coggins, L.W. and Parkinson, E.K. In vitro analysis of multistage squamous carcinoma : Defective terminal maturation is an early and ubiquitous event. In "Culture of Specialised Cells" Vol. 4 Culture of Tumour Cells (Freshney, R.I. ed), Alan R. Liss Inc. New York (2003) pp261-288.

Gordon, KE and Parkinson EK. Analysis of telomerase activity and telomere function in cancer. Methods Mol. Biol. (2004) 281: 333-348.

Research interests:

Professor Parkinson has continued his interests in the immortalization of human keratinocytes and his interest in telomerase (reviewed in McCaul et al Lancet Oncology 2002). He is particularly interested in the non-canonical functions of telomerase that have recently been shown to activate keratinocyte stem cell proliferation and migration and also to facilitate squamous neoplasia.  Professor Parkinson currently holds grants from Research Into Ageing, the EEC and the BBSRC, a support for science studentship award from the Institute of Dentistry and a School of Medicine studentship award.

In addition, Professor Parkinson is Head of Research for Clinical & Diagnostic Oral Sciences, the Blizard Building representative for GMO committee GM474 and the chair of the Blizard Building user’s group for GMO category II work.  Professor Parkinson currently supervises three PhD students.  He also annually supervises intercalated BSc students and MSc students and lectures on the Intercalated and Dental Diploma BSc courses as well as the MSc Molecular Pathology course. Professor Parkinson is responsible for organizing departmental seminars and the internal peer review system in addition to serving on the School of Medicine & Dentistry Board, the Blizard Building Local Management Committee, the Dental Institute Advisory Group, the Dental Sciences Research Group Steering Committee and the FACS user’s group.

Examples of research funding:

BBSRC; Research into Ageing; MRC via the School of Medicine & Dentistry; Support for Oral Science studentship.

Supervision:

I supervise Biancastella Cereser; Zacharoula Nikolakopoulou and Alice de Castro and am second supervisor of Gayani Pitiyage and Saira Athar. BSc Oral Biology and MSc Oral Pathology project students.

Undergraduate teaching:

BSc Oral Biology;BDS

Postgraduate teaching:

MSc Oral Pathology