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Institute of Dentistry - Barts and The London

Dr Hong Wan, PhD

Hong

Senior Lecturer in Cell Biology

Email: h.wan@qmul.ac.uk
Telephone: +44 (0) 20 7882 7139
Room Number: Blizard Institute

Profile

 

1978-83  BDS, School of Stomatology, West China University of Medical Sciences, Sichuan University,  China

1983-85  General Dentist, Zhongshan Hospital, Shanghai First Medical University, Shanghai, China1985-88  MSc in Prosthodontics, School of Stomatology, West China University of Medical Sciences, Sichuan  University, China

1988-91 Lecturer in Prosthetic Department, School of Stomatology, West China University of Medical Sciences, Sichuan University, China

1991-95  PhD in Department of Clinical Engineering, University of Liverpool

1996-99 Postdoctoral research fellow (Wellcome Trust funded), St. George’s Hospital Medical School, University of London

1999-2003   Postdoctoral research associate (Wellcome Trust funded), St. John’s Institute of Dermatology, St Thomas’ Hospital, UK

2004-2006  MRC fellow (funded by a MRC Career Development Fellowship for Stem Cell Research), Tumour Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, QMUL

2007-present  Non-clinical senior lecturer, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, QMUL

 

 


Centre: Centre for Oral Immunobiology and Regenerative Medicine

Teaching

Giving lectures/seminars to the 1st year BDS undergraduates, postgraduates of MSc-Experimental Oral Pathology, and biomedical life science students, on topics in biochemistry, histology, membrane biology, cell adhesion and migration, research in vesicular-bullous diseases.
Coaching students of MSc-Experimental Oral Pathology on the lab practical in immunofluorescence and western blotting.
Supervising the 3rd year BDS on SSC and students of SBS 206 Project Skills in the Life Sciences on dissertation.

Research

Research Interests:

Dr Wan’s research focuses on cell-cell junctions in health and disease. Cell-cell junctions are multimolecular adhesion complexes that are located at the plasma membrane of epithelial cells and play an essential role in the maintenance of tissue architecture and integrity. These junctions crosstalk one another and coordinate with a diversity of cellular processes such as proliferation, differentiation, morphogenesis, as well as motility. Increasing evidence indicates that many proteins in these junctions also act as sensors to environment mechanical cues in regulating various cell activities.
Our recent study has identified the desmosomal cadherin Desmoglein-3 (Dsg3) responds to cyclic strain and relays mechanical signals to YAP, a characterised mechanosensor and downstream effector of the Hippo pathway. Importantly, we have demonstrated that modulation of Dsg3 expression has a direct impact on the cell fate decision via the mechanism of regulating the fundamental pathways, such as p53, YAP and AP-1. Collectively, these findings underscore the unprecedented pivotal role of adhesion molecules in modulating a higher-ordered network essential for tissue renewal, regeneration, and homeostasis. Thus, it is crucial to elucidate the mechanism underlying these molecular events.
The insight from this study will not only advance our knowledge in cell biology but also have significant implications in further our understanding of the pathogenesis of various human diseases, including cancer and autoimmune blistering disease pemphigus. Our research is largely based on in vitro study by adopting different cell culture-based assays in oral and skin-derived keratinocyte lines with gain or loss of function approach for the target genes in conjunction with the pharmacological interventions. The ultimate goal is to translate our findings to clinical research and to improve diagnosis and clinical management of diseases that will benefit patient life and public health. 

Publications

Key Publications
Jutamas Uttagomol, Usama Sharif Ahmad, Ambreen Rehman, Yunying Huang, Ana C. Laly, Angray Kang, Jan Soetaert, Randy Chance, Muy-Teck Teh, John T. Connelly and Hong Wan. Evidence for the Desmosomal Cadherin Desmoglein-3 in Regulating YAP and Phospho-YAP in Keratinocyte Responses to Mechanical Forces.  Int. J. Mol. Sci. 2019, 20, 6221
Rehman A, Cai Y, Hünefeld C, Jedličková H, Huang Y, Teck Teh M, Sharif Ahmad U, Uttagomol J, Wang Y, Kang A, Warnes G, Harwood C, Bergamaschi D, Kenneth Parkinson E, Röcken M, Wan H. The desmosomal cadherin desmoglein-3 acts as a keratinocyte anti-stress protein via suppression of p53. Cell Death Dis. 2019 Oct 3;10(10):750. 
Moftah H, Dias K, Apu EH, Liu L, Uttagomol J, Bergmeier L, Kermorgant S, Wan H. Desmoglein 3 regulates membrane trafficking of cadherins, an implication in cell-cell adhesion. Cell Adh Migr. 2016 Jun 2:1-22. [Epub ahead of print]
Louise Brown, Ahmad Waseem, Isa, N. Cruz, Jaroslaw Szary, Emina Gunic, Tanima Mannan, Min Yang, Ferran Valderrama, Edel A. O’Toole and Hong Wan. Desmoglein 3 promotes cancer cell invasion through regulating AP-1 and PKC dependent-Ezrin activation. Oncogene. 2014 May 1;33(18):2363-74. 
Tsang SM, Brown L, Lin K, Liu L, Piper K, O'Toole EA, Grose R, Hart IR, Garrod DR, Fortune F, Wan H (2012) Non-junctional human desmoglein 3 acts as an upstream regulator of Src in E-cadherin adhesion, a pathway possibly involved in the pathogenesis of pemphigus vulgaris. J Pathol 227: 81-93.
Tsang SM, Brown L, Gadmor H, Gammon L, Fortune F, Wheeler A, Wan H (2012) Desmoglein 3 acting as an upstream regulator of Rho GTPases, Rac-1/Cdc42 in the regulation of actin organisation and dynamics. Exp Cell Res 318: 2269-2283.
Mannan T, Jing S, Foroushania SH, Fortune F, Wan H (2011) RNAi-mediated inhibition of the desmosomal cadherin (desmoglein 3) impairs epithelial cell proliferation. Cell Prolif. Aug;44(4):301-10.
Tsang SM, Liu L, Teh MT, Wheeler A, Grose R, Hart IR, Garrod DR, Fortune F, Wan H (2010) Desmoglein 3, via an interaction with E-cadherin, is associated with activation of Src. PLoS One. Dec 3;5(12):e14211.
Hong Wan, Ming Yuan, Cathy Simpson, Kirsty Allen, Nuzhat Baksh, Edel A O’Toole and Ian R Hart (2007) Stem/progenitor cell-like properties of Desmoglein 3dim cells in primary and immortalized keratinocyte lines. Stem Cells May;25(5):1286-97. Epub Jan 25.

Wan H, Stone MG, Simpson C, Reynolds LE, Marshall JF, Hart IR, Hodivala-Dilke KM, Eady RA (2003) Desmosomal proteins, including desmoglein 3, serve as novel negative markers for epidermal stem cell-containing population of keratinocytes. J Cell Sci. 116:4239-4248.

 

 

All Publications
2020 - Sihem Houacine, Angray Kang, Eric Kenneth Parkinson, Hong Wan, Farida Fortun. Induction of p53 in Keratinocyte Cultures Treated With Behçet's Patient Sera. J Oral Pathol Med. 2020 May;49(5):435-442.
2019 - Jutamas Uttagomol, Usama Sharif Ahmad, Ambreen Rehman, Yunying Huang, Ana C. Laly, Angray Kang, Jan Soetaert, Randy Chance, Muy-Teck Teh, John T. Connelly and Hong Wan. Evidence for the Desmosomal Cadherin Desmoglein-3 in Regulating YAP and Phospho-YAP in Keratinocyte Responses to Mechanical Forces.  Int. J. Mol. Sci. 2019, 20, 6221,
2019 - Xiao Li, Usama Sharif Ahmad, Yunying Huang, Jutamas Uttagomol, Ambreen Rehman, Ke Zhou, Gary Warnes, Simon McArthur, Eric Kenneth Parkinson and H Wan. Desmoglein-3 acts as an anti-ageing protein by suppressing reactive oxygen species and doming whilst augmenting the tight junctions in MDCK cells. Mechanism of Cell Ageing and Development. In press. https://doi.org/10.1016/j.mad.2019.111174
2019 - Rehman A, Cai Y, Hünefeld C, Jedličková H, Huang Y, Teck Teh M, Sharif Ahmad U, Uttagomol J, Wang Y, Kang A, Warnes G, Harwood C, Bergamaschi D, Kenneth Parkinson E, Röcken M, Wan H, The desmosomal cadherin desmoglein-3 acts as a keratinocyte anti-stress protein via suppression of p53. Cell Death Dis.
2019 Oct 3;10(10):750. - Apu EH, Akram SU, Rissanen J, Wan H, Salo T. Desmoglein 3 - influence on oral carcinoma cell migration and invasion. Exp Cell Res. 2018 Jun 30. 
2018.06.037. [Epub ahead of print]2018 - A. Rehman, Y. Cai, H. Jedliková, C. Harwood, D. Bergamaschi, H. Wan. 1347 Desmoglein-3 acts as an anti-stress protein via suppression of p53, J Invest Dermatol.
2018 - J. Uttagomol, A. Águedo, J. Connelly, H. Wan. 858 Desmoglein 3 acts as a mechanosensor in keratinocytes. 
2018 - Hong Wan. Cell-Cell Interactions in the Oral Mucosa: Chapter 2. Tight Junctions and Gap Junctions, edited by Lesley Bergmeier, publication in March 2018.
2018 - Hong Wan. Cell-Cell Interactions in the Oral Mucosa: Chapter 3. Adherens Junctions and Desmosomes, edited by Lesley Bergmeier, publication in March 2018.
2018 - Hong Wan. Desmoglein 3, an invited review article in Encyclopedia of Signaling Molecules, 2nd Edition, edited by Sangdun Choi, Encyclopedia of Signaling Molecules, pg 1352 to 1366. 12th Jan 2018 (https://www.amazon.co.uk/Encyclopedia-Signaling-Molecules-Sangdun-Choi/dp/1493967991)
2016 - Wan H. Desmoglein 3 acts as a potential oncogene in promoting cancer cell migration and invasion through regulating AP-1 and PKC dependent-Ezrin activation. 13 Oct 2016 - Br J Dermatol
2016 Oct;175 Suppl 2:65-66. doi: 10.1111/bjd.14911. British Skin Foundation, Skin Deep - 20 Years of Research, 20th Anniversary Conference
2016 – Jed Yu Jie Lee and Hong Wan. Application of Immunofluorescence in the Diagnosis of Oral Diseases. Journal of Dentistry and Oral Biologyhttps://www.researchgate.net/publication/316989964_Application_of_Immunofluorescence_in_the_Diagnosis_of_Oral_Diseases Jan 2017
2016 - Hong Ma, Haiyan Dai, Xiaofeng Duan, Zhenglong Tang, Rui Liu, Kunjun Sun, Ke Zhou, Hao Chen, Hang Xiang, Jinsheng Wang, Qiong Gao, Yuan Zou, Hong Wan and Muy-Teck. The. Independent Evaluation of a FOXM1-based Quantitative Malignancy Diagnostic System (qMIDS) on Head and Neck Squamous Cell Carcinomas. Oncotarget.
2016 Aug 23;7(34):54555-54563. doi: 10.18632/oncotarget.10512.2016 - Moftah H, Dias K, Apu EH, Liu L, Uttagomol J, Bergmeier L, Kermorgant S, Wan H. Desmoglein 3 regulates membrane trafficking of cadherins, an implication in cell-cell adhesion. Cell Adh Migr. 2016 Jun 2:1-22. [Epub ahead of print]
2015 - Brown L and Wan H. Desmoglein 3: a help or a hindrance in cancer progression? Cancers (Basel). 2015 Jan 26;7(1):266-86. doi: 10.3390/cancers70102662015 - Hong Wan, Kuang Lin, Sui Man Tsang, Jutamas Uttagomol. Evidence for Dsg3 in regulating Src signaling by competing with it for binding to caveolin-1. Data in Brief, Volume 6, March 2016, Pages 124–134. doi:10.1016/j.dib.2015.11.049
2014- Hong Wan. Discovery drug targets, International Innovation, Issue 140:10-112013 - Louise Brown, Ahmad Waseem, Isa, N. Cruz, Jaroslaw Szary, Emina Gunic, Tanima Mannan, Min Yang, Ferran Valderrama, Edel A. O’Toole and Hong Wan. Desmoglein 3 promotes cancer cell invasion through regulating AP-1 and PKC dependent-Ezrin activation. Oncogene. 2014 May 1;33(18):2363-74. doi: 10.1038/onc.2013.186. Epub 2013 Jun 10
2012 - Teh MT, Hutchison IL, Costea DE, Neppelberg E, Liavaag PG, Purdie K, Harwood C, Wan H, Odell EW, Hackshaw A, Waseem A. Exploiting FOXM1-orchestrated molecular network for early squamous cell carcinoma diagnosis and prognosis. Int J Cancer. 2013 May 1;132(9):2095-106. doi: 10.1002/ijc.27886. Epub 2012 Oct 25.
2012 - Bose A, Teh MT, Hutchison IL, Wan H, Leigh IM, Waseem A. Two mechanisms regulate keratin K15 expression in keratinocytes: role of PKC/AP-1 and FOXM1 mediated signalling. PLoS One. 2012;7(6):e38599. doi: 0.1371/journal.pone.0038599. Epub
2012 Jun 27.2012 - Tsang SM, Brown L, Lin K, Liu L, Piper K, O'Toole EA, Grose R, Hart IR, Garrod DR, Fortune F, Wan H (2012b) Non-junctional human desmoglein 3 acts as an upstream regulator of Src in E-cadherin adhesion, a pathway possibly involved in the pathogenesis of pemphigus vulgaris. J Pathol 227: 81-93.
2012 - Tsang SM, Brown L, Gadmor H, Gammon L, Fortune F, Wheeler A, Wan H (2012a) Desmoglein 3 acting as an upstream regulator of Rho GTPases, Rac-1/Cdc42 in the regulation of actin organisation and dynamics. Exp Cell Res 318: 2269-2283.
2011 - Mannan T, Jing S, Foroushania SH, Fortune F, Wan H. RNAi-mediated inhibition of the desmosomal cadherin (desmoglein 3) impairs epithelial cell proliferation. Cell Prolif. Aug;44(4):301-10
2011 - Teh MT, Parkinson EK, Thurlow JK, Liu F, Fortune F, Wan H. A molecular study of desmosomes identifies a desmoglein isoform switch in head and neck squamous cell carcinoma. J Oral Pathol Med. Jan;40(1):67-76.
2010 - Tsang SM, Liu L, Teh MT, Wheeler A, Grose R, Hart IR, Garrod DR, Fortune F, Wan H. Desmoglein 3, via an interaction with E-cadherin, is associated with activation of Src. PLoS One. Dec 3;5(12):e14211.
2010 - Gemenetzidis E, Elena-Costea D, Parkinson EK, Waseem A, Wan H, Teh MT. Induction of human epithelial stem/progenitor expansion by FOXM1. Cancer Res. Nov 15;70(22):9515-26.
2010 - Cabral RM, Wan H, Cole CL, Abrams DJ, Kelsell DP, South AP. Identification and characterization of DSPIa, a novel isoform of human desmoplakin. Cell Tissue Res. Jul;341(1):121-9. Epub
2010 Jun 4.2009 - Gemenetzidis E, Bose A, Riaz AM, Chaplin T, Young BD, Ali M, Sugden D, Thurlow JK, Cheong SC, Teo SH, Wan H, Waseem A, Parkinson EK, Fortune F, Teh MT. 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. Epub
2009 Mar 16.2007 - Hong Wan, Ian Mackenzie. Keratinocyte stem cells are marked by low expression of desmoglein 3. J Stomatol InvestJan-Dec Vol 1(No 1):37-40.
2007 - Hong Wan, Ming Yuan, Cathy Simpson, Kirsty Allen, Nuzhat Baksh, Edel A O’Toole and Ian R Hart. Stem/progenitor cell-like properties of Desmoglein 3dim cells in primary and immortalized keratinocyte lines. Stem Cells May;25(5):1286-97. Epub Jan 25.
2007 - Hong Wan, Andrew P South and Ian R Hart. Increased keratinocyte proliferation initiated through downregulation of desmoplakin by RNA interference. Exp Cell Res 2007 Jul 1;313(11):2336-44. Epub Jan 30.
2004 - Wan H, Dopping-Hepenstal-PJC, Gratian-MJ, Stone-MG, Zhu-G, Purkis-PE,South-AP, Keane-F, Armstrong-DKB, Buxton-RS, McGrath-JA, Eady-RAJ. Striate palmoplantar keratoderma arising from desmoplakin and desmoglein 1 mutations is associated with contrasting perturbations of desmosomes and the keratin filament network. Br J Dermatol. 150(5),878-891
2003 - Wan H, Stone MG, Simpson C, Reynolds LE, Marshall JF, Hart IR, Hodivala-Dilke KM, Eady RA. Desmosomal proteins, including desmoglein 3, serve as novel negative markers for epidermal stem cell-containing population of keratinocytes. J Cell Sci. 116:4239-4248.
2003 - Andrew P South, Hong Wan, Michael G. Stone, Patricia J.C. Dopping-Hepenstal, Patrcia E. Purkis, John F. Marshall, Irene Leigh, Robin A.J. Eady, Ian R. Hart and John A. McGrath. Lack of plakophilin 1 increases keratinocyte migration and reduces desmosome stability. J Cell Sci.  116:3303-14.
2003 - H Wan, T Dopping-Hepenstal, M Gratian, MG. Stone, JA. McGrath and RAJ Eady. Desmosome Expression Exhibits Site-Specific Feature in Human Palmar Skin. Exp. Dermatol. Aug;12(4):378-88.
2002 - Whittock NV, Smith FJ, Wan H, Mallipeddi R, Griffiths WA, Dopping-Hepenstal P, Ashton GH, Eady RA, McLean WH, McGrath JA. Frameshift mutation in the V2 domain of human keratin 1 results in striate palmoplantar keratoderma. J Invest Dermatol. May;118(5):838-44.
2002 - Whittock NV, Wan H, Morley SM, Garzon MC, Kristal L, Hyde P, McLean WH,Pulkkinen L, Uitto J, Christiano AM, Eady RA, McGrath JA. Compound heterozygosity for non-sense and mis-sense mutations in desmoplakin underlies skin fragility/woolly hair syndrome. J Invest Dermatol. Feb;118(2):232-8
2001 - Springall T, Sheerin NS, Abe K, Holers VM, Wan H, Sacks SH. Epithelial secretion of C3 promotes colonization of the upper urinary tract by Escherichia coli. Nature Medicine. Jul;7(7):801-6.
2001 - H Wan, HL Winton, C Soeller, ER Tovey, DC Gruenert, PJ Thompson, GA Stewart, GW Taylor, DR Garrod, MB Cannell, and C Robinson: The transmembrane protein occludin of epithelial tight junctions is a functional target for serine peptidases from fecal pellets of Dermatophagoides pteronyssinus. Clin Exp Allergy. Feb;31(2):279-94.
2000 - H Wan, HL Winton, C Soeller, ER Tovey, DC Gruenert, PJ Thompson, GA Stewart, GW Taylor, DR Garrod, MB Cannell, and C Robinson: Quantitative structure and biochemical analysis of tight junction dynamics following exposure of epithelial cells to house dust mite allergen Der p 1. Clin Exp Allergy. May;30(5):685-98
2000 - H Wan, HL Winton, C Soeller, GA Stewart, PJ Thompson, DC Gruenert, MB Cannell, DR Garrod, and C Robinson: Tight junction properties of the immortalized human bronchial epithelial cell lines Calu-3 and 16HBE14o-. Eur Respir J. Jun;15(6):1058-68
2000 - PC Ring, H Wan, C Schou, AK Kristensen, P Roepstorff and C Robinson: The 18Da form of cat allergen Felis Domesticus 1 (Fel d 1) is associated with gelatin- and fibronectin-degrading activity. Clin Exp Allergy. Aug;30(8):1085-96.
1999 - H Wan, HL Winton, C Soeller, ER Tovey, DC Gruenert, PJ Thompson, GA Stewart, GW Taylor, DR Garrod, MB Cannell and C Robinson: Disruption of epithelial tight junctions by house dust mite faecal pellet proteinase. Journal of Clinical Investigation, 104(1), 123-133. Confocal images are used in front cover of the issue.
1998 - HL Winton, H Wan, MB Cannell, PJ Thompson, DR Garrod, GA Stewart, C Robinson: Cell lines of pulmonary and non-pulmonary origin as tools to study the effects of house dust mite proteinases on the regulation of epithelial cell permeability. Clin Exp Allergy, 28,1273-85.
1998 - HL Winton, H Wan, MB Cannell, PJ Thompson, DR Garrod, GA Stewart and C Robinson: Class specific inhibition of house dust mite proteinases which cleave cell adhesion, induce cell death and which increase the permeability of lung epithelium. British Journal of Pharmacology, 124,1048-59.
1997 - H. Wan, R. Williams, P. Doherty and D.F. Williams: A study of cell behaviour on the surfaces of multifilament. Journal of Material Sciences: Material in Medicines, 8(1), 45-51. A SEM photogragh is used in the front cover of the issue.
1994 - H. Wan, R. Williams, P. Doherty and D.F. Williams: The cytotoxicity evaluation of Kevlar and silicon carbide by MTT assay. Journal of Material Science: Material in Medicine, 5, 441-445

 

 

 

 

Supervision

Research student supervision

 

Supervising project research students at all levels, including PhD, MSc - Experimental Oral Pathology/Regenerative Medicine, iBSc-Orla Biology.

So far, have supervised 7 PhDs and more than 20 MSc/iBSc students since 2007.