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Institute of Dentistry

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Dr Hong Wan, PhD

Hong

Senior Lecturer in Cell Biology

Email: h.wan@qmul.ac.uk
Telephone: +44 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, China

1985-88                  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

2004-06                  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

 

Teaching

Holder of National Teaching Fellowship Award since 2016

Undergraduate/postgraduate teaching to the 1st year/4th year BDS, iBSc-OB/MSc-EOP, 1st Biomedical Life Science students and giving lecturers covering topics in biochemistry, membrane biology, histology, tooth developmental anomalies, research in oral blistering diseases and lab practical to MSc-EOP, iBSc and 4th year BDS.

Mentor for BDS-SSC, SBS Project Skills in the Life Sciences as well as a personal tutor for the QMUL Model in year 1 BDS students.

Module lead for iBSc-Oral Biology module M4 "Research Skills".

Research

Research Interests:

Our research is focused on cadherin signalling and cell-cell adhesions in health and disease, in particular on the biological functions of desmosomal adhesion protein known as pemphigus vulgaris antigen (PVA) or Desmoglein-3 (Dsg3). Cell-cell junctions including desmosomes and adherens junctions are abundant in epithelial tissues in the skin and oral mucosa that experience extensive mechanical stress. These junctions are the essential scaffolding structures in maintaining tissue integrity and are coordinating with many cellular activities such as proliferation, differentiation, polarisation and morphogenesis as well as cell survival. The importance of Dsg3 in cell-cell adhesions is underscored in pemphigus vulgaris in which Dsg3 serves as a major target of autoantibodies, leading to the defect in cell-cell adhesions and blistering in the skin and oral mucosa.

In addition, Dsg3 is also found to be upregulated in cancers in various organs of the body, including the head and neck, lungs, esophageal and skin. However, the actual role of Dsg3 in cancer is much less elucidated. Increasing evidence suggests that Dsg3 plays an important role in cell signalling and regulates pathways in epithelial cells, involved in cell shape change; motility, proliferation, differentiation, and morphogenesis (see a few examples in the figure). Thus, Dsg3 is considered to be a signalling molecule that functions beyond the desmosome adhesion. Understanding the molecular mechanism of how Dsg3 regulates these signalling pathways and their interplay with cell-cell junctions and the epithelial fate decision is crucial in advance our knowledge in Dsg3 biology and also in the pathophysiology of its associated diseases such as pemphigus and cancer.

 

Publications

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. doi: 10.1038/onc.2013.186. Epub 2013 Jun 10.

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.

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.

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.

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.

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.

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.

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.

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.

Publications

2018 - Apu EHAkram SURissanen JWan HSalo T. Desmoglein 3 - influence on oral carcinoma cell migration and invasion. Exp Cell Res. 2018 Jun 30. pii: S0014-4827(18)30379-3. doi: 10.1016/j.yexcr.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. DOI: https://doi.org/10.1016/j.jid.2018.03.1364

2018 - J. Uttagomol, A. Águedo, J. Connelly, H. Wan. 858 Desmoglein 3 acts as a mechanosensor in keratinocytes. DOI: https://doi.org/10.1016/j.jid.2018.03.869

2018 - Hong Wan. Cell-Cell Interactions in the Oral Mucosa: Chapter 2. Tight Junctions and Gap Junctions, edited by Lesley Bergmeier, Proof submitted in Dec 2017, publication in March 2018.

2018 - Hong Wan. Cell-Cell Interactions in the Oral Mucosa: Chapter 3. Adherens Junctions and Desmosomes, edited by Lesley Bergmeier, Proof submitted in Dec 2017, 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 Biology

https://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/cancers7010266

2015 - 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 140:10-11

2013 - 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 Invest Jan-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.

PhD Supervision

Research student supervision

Supervisor for research students at all levels, including PhD, MSc-EOP/Regenerative Medicine, iBSc-OB and have supervised 6 PhDs and 19 MSc/iBSc and 3 visiting scholars since 2007.

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