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

Lecturer in Head and Neck Cancer

Contact details

I obtained my BSc (Hons) degree in Biomedical Science (1996) and PhD in Cell & Molecular Physiology at King’s College London (2000) investigating cellular and molecular pharmacology of melatonin receptor signal transduction and intracellular pigment vesicle transport mechanism in Xenopus melanophores under the supervision of Dr David Sugden. 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 under the guidance of Prof Anthony Quinn. My second Cancer Research UK postdoctoral fellowship was supervised by Prof. David Kelsell and Prof. Michael Philpott, to further my research investigating WNT/beta-catenin signalling and genome-wide signatures (SNP and LOH) 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 research program investigating the 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.

Publications:

Key Publications

  • 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)
  • Teh MT, Parkinson EK, Thurlow JK, Liu F, Fortune F and Wan H (2010) A molecular study of desmosomes identifies a desmoglein isoform switch in head and neck squamous cell carcinoma. J. Oral Pathol. Med.
  • 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 Oncology46(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. Carcinogenesis31(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.
  • Tilakaratne WM, Iqbal Z, Teh MT, Ariyawardana A, Pitiyage G, Cruchley A, Pavli EH, Lalli A, Waseem A, Parkinson EK, Fortune F (2008) Up regulation of HIF-1a in malignant transformation of oral submucous fibrosis. J. Oral Pathol. Med. 37:372-377.
  • Lalli A, Tilakaratne WM, Ariyawardena A, Leigh IM, Hagi-Pavli E, Cruchley A, Parkinson EK, Teh MT, Fortune F and Waseem A (2008) An altered keratinocyte phenotype in oral submucous fibrosis: correlation of keratin K17 expression with disease severity. J. Oral Pathol. Med. 37:211-220.
  • Purdie KJ, Lambert SR, Teh MT, Chaplin T, Molloy G, Raghavan M, Kelsell DP, Harwood CA, Proby CM, Young BD (2007) Allelic Imbalances and Chromosome 9p Microdeletion Demonstrated in Cutaneous Squamous Cell Carcinomas Using Single Nucleotide Polymorphism Microarray Analysis. Genes Chromosomes Canc. 46:661-669.
  • 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.


(Click here for a list of all my publications)

Research interests:

Research interests:

Molecular Cancer Diagnosis & Personalised Medicine

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.

Early Cancer Biomarkers

During my first postdoc, I investigated Sonic Hedgehog (Shh) signalling in basal cell carcinoma. We published the first evidence that a transcription factor FOXM1 was a target of Shh signalling and has a direct role in human cancer (2002). Since then, the field of FOXM1 has expanded significantly and the role of FOXM1 in cancer is well established but its oncogenic mechanism remains unclear. In 2009, we published the first evidence that upregulation of FOXM1 is an early oncogenic signal which precedes cancer progression. We also showed that nicotine can cause malignant transformation through cooperation with FOXM1. This publication drew public attention (Press releases: Times; Guardian; MRC; NHS; Cancer Research UK) especially the tobacco replacement therapy community. We have shown that excessive FOXM1 expression leads to de novo genomic instability which induces malignant transformation by activating CEP55 (a centrosomal protein involved in cytokinesis) and HELLS (a helicase/stem-cell marker involved in epigenetic regulation). We were the first to demonstrate that CEP55 is a direct promoter target of FOXM1. Soon after, several papers independently established a causal link between CEP55 and oral SCC, lung adenocarcinoma, breast carcinoma and aberrant cytokinesis. Collectively, FOXM1 and its target genes CEP55 and HELLS hold great promise as cancer diagnostic biomarkers not only for oral cancer but potentially applicable to many other cancer types given that FOXM1 is overexpressed in almost all cancer types. Currently, we are investigating the roles of CEP55 and HELLS in epithelial cells.

Mechanism of Cancer Initiation by 'Hijacking' Stem Cells

It is now well established that most human cancers express high levels of FOXM1 but the reason for this was unclear until we published a pioneering study in Cancer Research (2010) (Press release article, The Independent) demonstrating that FOXM1 ‘hijacks’ the inherent self-renewal property of stem cells to initiate cancer formation. The study have demonstrated for the first time using adult human stem cells isolated from mouth tissues that normal stem cells engineered using retrovirus to express abnormal levels of FOXM1 gene triggers excessive cell growth within a 3D tissue culture model system which was established to replicate human tissue regeneration in the laboratory. The 3D tissue culture system allows scientists to perform research on manipulated human cells without evoking ethical issues associated with using human subjects or animals. Stem cells expressing normal levels of the gene did not cause excessive cell growth. The abnormal growth triggered by FOXM1 resulted in a condition resembling hyperplasia – an early hallmark of pre-cancer. This is thought to represent the very first step of a series of abnormal molecular events leading to cancer formation. Understanding how FOXM1 exploits stem cells to jumpstart cancer initiation has profound implication for improving early cancer diagnosis and therapeutic interventions that target cancer initiation at its earliest incipient stage.


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. We hypothesised that FOXM1 mediates a window of cancer susceptibility in the progenitor cells whereby anticancer therapeutic intervention at this stage may prevent cancer initiation.

Undergraduate teaching:

Dr. Teh is actively involved in teaching cell and molecular biology components of various undergraduate courses such as BDS Fundamentals of Dentistry Cell Biology, Intercalated BSc in Oral Biology. Dr Teh also supervises BSc experimental projects.

Postgraduate teaching:

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, diagnostic markers for cancer stem cells, mechanism of cancer stem cell initiation, quantitative study of epigenomic fingerprints in cancer stem cells as potential biomarkers for personalised medicine, etc.