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Institute of Dentistry

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Professor Ian Mackenzie

Ian

Professor of Stem Cell Science

Email: i.c.mackenzie@qmul.ac.uk
Telephone: +44 20 7882 7159
Room Number: Blizard Building

Profile

Professor Ian Mackenzie studied initially at Queen Mary and then trained in Dentistry at the London Hospital Medical and Dental School. He then did various house surgeon and registrar jobs in oral surgery at The London Hospital Oral Surgery and studied for his Fellowship at the Royal College of Surgeons, England. He subsequently did a PhD in Oral Pathology. He then moved to the USA for over twenty years, directing research institutes at the Universities of Iowa and Texas. He then moved to the University of Michigan where he was a member of the Comprehensive Cancer Center. Before returning to London, he was Vice Dean for Research at the University of Wales School of Medicine and Dentistry in Cardiff. During studies for his PhD he developed interests in the cellular mechanisms involved in the maintenance of skin and oral mucosa and these remain the basis of his continuing interests in stem cells, tissue renewal, and cancer.

Research

Research Interests:

Ian Mackenzie's research interests relate mainly to mechanisms that control normal and pathological epithelial differentiation and spatial organization with particular interests in periodontal structure, the identification, renewal, and characterisation of somatic stem cells, and the behaviour stem cell in malignant tissues.

Currently his group investigates various aspects of the normal and pathological behaviour of epithelial stem cells in relation to cell renewal, tissue engineering and cancer. Work examines the potential value of re-differentiation of somatic stem cells in tissue engineering and the roles of oxygen in stem cell survival, but the current major interest of the group is the hierarchical pattern of stem cell proliferation demonstrable in oral malignancies. Work examines how stem cell properties affect the initiation and growth of malignant lesions and the nature of the molecular mechanisms controlling asymmetric stem cell divisions and phenotypic stability. Recent work has focused on the role of epithelial-mesenchymal-transition (EMT) in endowing malignant stem cells with motility, an attribute particularly important for initiating tumour metastasis and generating therapeutic resistance. These motile cells are observed escaping from stationary colonies of cells in vitro and are easily identifiable by their elongated morphologies and antibody staining patterns. It has been shown that EMT of cancer stem cells is markedly enhanced by hypoxia and by various cytokines, findings that relate roles of stroma to modulation of stem cell behaviour and tumour recurrence. The group is funded by MRC/NC3Rs, Barts and The London Charitable Foundation, the Saving Faces Research Foundation, and the Fanconi Anemia Research Fund.

Publications

Key Publications

Wray H, Harper L, Mackenzie IC, Storey A, Navsaria H. α6 integrin and CD44 enrich for normal keratinocyte stem-like cells that display apoptotic resistance. Plos One. In press

Biddle A, Mackenzie IC. Cancer stem cells and EMT in carcinoma. Cancer Metastasis Rev. 2012 Feb 3. [Epub ahead of print]

Biddle A, Liang X, Gammon L, Fazil B, Harper LJ, Emich H, Costea DE, Mackenzie IC. Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative.
Cancer Res. 2011 Aug 1;71(15):5317-26.

Harper L, Costea DE, Gammon L, Biddle A, Mackenzie IC. Normal and malignant epithelial cells with stem-like properties have an extended G2 cell cycle phase that is associated with apoptotic resistance. (2010). BMC Cancer. (in press).

Gammon L, Biddle A, Harper L, Fazil BI, Mackenzie IC. Stem cell characteristics of sub-populations in cell lines derived from head and neck cancers of Fanconi Anemia patients. (2010)  J. Oral Pathol. Med. (in press).

Costea DE, Gammon L, Kitajima K, Harper L, Mackenzie IC. Epithelial stem cells and malignancy. J Anat. 2008 Jul;213(1):45-51.

Mackenzie IC. Cancer stem cells. Ann Oncol. 2008 Jul;19 Suppl 5:v40-3.

Locke M, Hyland PL, Irwin CR, Mackenzie IC. Modulation of gingival epithelial phenotypes by interactions with regionally defined populations of fibroblasts. J Peridontal Res. 2008 Jun;43(3):279-89.

Harper L, Piper K, Common J, Fortune F, Mackenzie IC. Stem cell patterns in cell lines derived from head and neck squamous cell carcinoma. J Oral Pathol. Med. 2007 Nov;36(10):594-603.

Tudor D, Chaudry F, Harper L, Mackenzie IC. The in vitro behaviour and patterns of colony formation of murine epithelial stem cells. Cell Prolif. 2007 Oct;40(5):706-20.

Costea DE, Tsinkalovsky O, Vintermyr OK, Johannessen AC, Mackenzie IC. Cancer stem cells- new and potentially important targets for the therapy of oral squamous cell carcinoma. Oral Dis. 2006 Sep;12(5):443-54.

Mackenzie IC. Stem cell properties and epithelial malignancies. Eur J Cancer. 2006 Jun;42(9):1204-12. Epub 2006 Apr 27.

Mackenzie IC. Retention of stem cell patterns in malignant cell lines. Cell Prolif. 2005 Dec;38(6):347-55.

Locke M, Heywood M, Fawell S, Mackenzie IC. Retention of intrinsic stem cell hierarchies in carcinoma-derived cell lines. Cancer Res. 2005 Oct 1;65(19):8944-50.

Tudor D, Locke M, Owen-Jones E, Mackenzie IC. Intrinsic patterns of behavior of epithelial stem cells. J Investig Dermatol Symp Proc. 2004 Sep;9(3):208-14. Review.

Mackenzie IC. Growth of malignant oral epithelial stem cells after seeding into organotypical cultures of normal mucosa. J Oral Pathol Med. 2004 Feb;33(2):71-8.

Mackenzie IC. Retroviral transduction of murine epidermal stem cells demonstrates clonal units of epidermal structure. J Invest Dermatol. 1997 Sep;109(3):377-83.

Mackenzie IC, Mackenzie SL, Rittman GA. Isolation of subpopulations of murine epidermal cells using monoclonal antibodies against differentiation-related cell surface molecules.Differentiation. 1989 Aug;41(2):127-38.

Mackenzie IC, Bickenbach JR. Label-retaining keratinocytes and Langerhans cells in mouse epithelia. Cell Tissue Res. 1985;242(3):551-6.

Mackenzie IC, Hill MW. Connective tissue influences on patterns of epithelial architecture and keratinization in skin and oral mucosa of the adult mouse. Cell Tissue Res. 1984;235(3):551-9.

Mackenzie IC. Relationship between mitosis and the ordered structure of the stratum corneum in mouse epidermis. Nature. 1970 May 16;226(5246):653-5.

PhD Supervision

Opportunities are available for laboratory or clinical studies of cancer stem cells.

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