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Institute of Dentistry

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Dr Muy-Teck Teh, PhD, BSc. (Hons.)

Muy-Teck

Senior Lecturer in Head and Neck Cancer

Email: m.t.teh@qmul.ac.uk
Telephone: +44 20 7882 7140
Room Number: Blizard Building

Profile

I obtained my BSc (Hons.) degree in Biomedical Science (1996) and subsequently a PhD in Cell & Molecular Physiology at King’s College London (2000) investigating molecular pharmacology of melatonin receptor signalling and melanin pigment vesicle transport mechanism in Xenopus melanophores. I then secured a Wellcome Trust postdoctoral position at the Centre for Cutaneous Research (Blizard Institute of Cell & Molecular Science), investigating the link between Hedgehog/Gli signalling and FOXM1 activation in human epidermal keratinocytes. My second Cancer Research UK postdoctoral fellowship investigated WNT/beta-catenin signalling and genome-wide signatures (SNP, LOH and CNV) in various congenital human epithelial diseases and sporadic basal and squamous cell carcinomas. In 2005, I was appointed my current lectureship position at the Centre for Clinical & Diagnostic Oral Sciences where I now lead a clinical translational research program based on basic research in molecular programming of adult epithelial stem cell renewal, differentiation and senescence.

Awards

I have received awards from the Association for International Cancer Research (AICR) and Barts & the London Charitable Foundation, University of London Senate House, Royal Society, Wellcome Trust and Medical Research Council (MRC). My research work has been published in internationally renowned journals such as Nature Genetics, Cancer Research, Journal of Cell Science, American Journal of Human Genetics, Molecular Cancer, Genes Chromosomes & Cancer and PLoS ONE. My research in the oncogene FOXM1 has recently been awarded the “Molecule of the Year 2010”. I have been appointed an academic editor for the journal PLoS ONE.

Research

Research Interests:

My key research aims to translate basic science into clinical applications and towards personalised medicine based on a combination of patient’s genetic (eg., mutation, SNP, LOH, CNV), epigenetic (DNA methylation/histone marks) and gene expression (mRNA levels) signatures. I believe that the key to successful cancer treatment and cure is early detection of cancer formation and personalised treatment based on individual’s molecular profile. Hence, I aim to delineate the mechanisms and identify molecular markers of early cancer initiation by employing my expertise in various molecular and cell culture techniques such as high-resolution DNA microarray ‘SNP fingerprinting’ technique, epigenomics (genome-wide methylome mapping, methylation specific qPCR), adult stem cell cultures, 3D organotypic tissue regeneration, retroviral gene delivery, RNA interference gene silencing, absolute real-time quantitative PCR, and bioinformatics. I am currently investigating the mechanism of oncogene-induced epigenetic modifications that perturbs the molecular program regulating stem cell renewal, differentiation and senescence. The stable and heritable properties of epigenetic ‘fingerprints’ render these signatures potentially important for clinical translation into diagnostic biomarkers.

A schematic model showing the mechanism for FOXM1-induced expansion of epithelial stem/progenitor compartment. We have previously shown that environmental factors such as nicotine and ultraviolet light can directly activate endogenous FOXM1 (1st oncogenic hit) in primary human oral and skin keratinocytes, respectively. We have shown that aberrant upregulation of FOXM1 in epithelial stem cells produce progenitor cells with enhanced proliferative capacity which impacts on terminal differentiation, resulting in a hyperplastic phenotype displaying perturbed differentiation characteristics. The deregulated differentiation pathway found in hyperplastic tissues may predispose the ‘expanded’ stem/progenitor compartment to subsequent ‘2nd’ oncogenic hit necessary for malignant conversion. I hypothesised that FOXM1 mediates a window of cancer susceptibility in the progenitor cells whereby anticancer therapeutic intervention at this stage may prevent cancer initiation.

Publications

Key Publications

Teh MT. Stem Cells and Cancer Stem Cells: Therapeutic Applications in Disease and Injury, Volume 3, Chapter 14: Initiation of Human Tumourigenesis: Upregulation of FOXM1 Transcription Factor. Edited by Dr. M.A. Hayat (Publisher: Springer). 2012. DOI 10.1007/978-94-007-2415-0 (In press)

Gemenetzidis E, Elena-Costea D, Parkinson EK, Waseem A, Wan H and Teh MT (2010) Induction of Human Epithelial Progenitor Expansion by FOXM1. Cancer Res 70(22):9515–9526 (Press release article, The Independent, Molecule of the Year 2010)

Waseem A, Ali M, Odell EW, Fortune F and Teh MT (2010) Downstream Targets of FOXM1: CEP55 and HELLS are Cancer Progression Markers of Head and Neck Squamous Cell Carcinoma. Oral Oncology 46(7):536-42.

Wang H, Teh MT, Ji YM, Patel Y, Firouzabadian S, Patel AA, Gutkind JS and Yeudall AW (2010) EPS8 Upregulates FOXM1 Expression, Enhancing Cell Growth and Motility. Carcinogenesis 31(6):1132-41.

Teh MT, Gemenetzidis E, Chaplin T, Young BD, Adiam WB, Sugden D and Philpott MP (2010) Upregulation of FOXM1 Induces Genomic Instability in Human Keratinocytes. Mol Cancer 9:45.

Gemenetzidis E, Bose A, Riaz MA, Chaplin T, Young BD, Ali M, Thurlow JK, Cheong SC, Teo SH, Sugden D, Wang H, Waseem A, Parkinson EK, Fortune F and Teh MT. (2009) FOXM1 Upregulation is an Early Event in Human Squamous Cell Carcinoma and it is Enhanced by Nicotine during Malignant Transformation. PLoS ONE 4(3):e4849. (Press releases: Times; Guardian; NHS; MRC;Cancer Research UK)

Teh MT, Tilakaratne WM, Chaplin T, Young BD, Ariyawardana A, Pitiyage G, Lalli A, Stewart JE, Hagi-Pavli E, Cruchley A, Waseem A, Parkinson EK and Fortune F. (2008) Fingerprinting Genomic Instability in Oral Submucous Fibrosis J. Oral Pathol. Med. 37:430-436.

Teh MT, Blaydon D, Ghali LR, Edmunds S., Pantazi E, Barnes MR, Kelsell DP & Philpott MP (2007) Role for non-canonical WNT16B in human epidermal keratinocyte proliferation and differentiation. J. Cell Sci. 120:330-339.

Blaydon D, Ishii Y, O’Toole1 EA, Unsworth HC, Teh MT, Rüschendorf  F, Sinclair C, Hopsu-Havu VK, Tidman N, Moss C,  Watson R, Berker D, Wajid M, Christiano AM, Kelsell DP. (2006) R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signalling, is mutated in inherited anonychia. Nat. Genet. 38:1245-1247.

Teh MT, Blaydon D, Tracy Chaplin, Nicola J. Foot, Spyros Skoulakis, Manoj Raghavan, Catherine A. Harwood, Charlotte M. Proby, Michael P. Philpott, Bryan D. Young and David P. Kelsell (2005) Genome-wide SNP Microarray Mapping in Basal Cell Carcinomas Unveils Uniparental Disomy as a Key Somatic Event. Cancer Res. 65:8597-8603. (Press release: BBC News)
Kelsell DP, Norgett EE, Unsworth H, Teh MT, Cullup T, et al. (2005) Mutations in ABCA12 underlie harlequin ichthyosis, the most severe congenital ichthyosis. Am J. Hum. Genet. 76:794-803. (Press release: BBC News)

·Teh MT, Wong S-T, Neill GW, Ghali LR, Philpott MP & Quinn AG. (2002) FOXM1 is a downstream target of Hedgehog signalling in basal cell carcinomas. Cancer Research, 62:4773-4780.

PhD Supervision

Dr. Teh actively involved in PhD and MSc supervision on research projects in the field of both basic and translational research. Past research projects include: the cellular and molecular effects of tobacco/betel quid alkaloids on oral mucosal keratinocytes in culture, therapeutic potential of oncogene-silencing using RNA interference in oral cancer, identification of diagnostic/prognostic biomarkers for early oral cancer detection, mechanism of cancer stem cell initiation, quantitative study of epigenomic fingerprints in cancer stem cells as potential biomarkers for personalised medicine, etc. We welcome informal email enquiries regarding potential research projects under Dr Teh's supervision.

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