Dr Hong Wan, PhD

Profile
Publications
Research

Non-clinical Senior Lecturer

Biography

Dr Wan was qualified as a dentist in China. After eight years working in clinic, Dr Wan moved to research and obtained her Ph.D in 1995 at The Faculty of Medicine, University of Liverpool. Her first postdoctoral post was funded by the Wellcome Trust in St. George’s Hospital Medical School, University of London investigating the effect of the proteases of house dust mite allergens on tight junctions in bronchial epithelium. In 1999 she joined a team at St John’s Institute of Dermatology, St Thomas’ Hospital, London, working on hereditary skin disorder caused by mutations in desmosome genes, research funded by a Wellcome Trust Research Program. During this study, she made an interesting observation on the low frequency of desmosome occurrence in the putative region of epidermal stem cells. From this she developed a novel strategy using Desmoglein 3 as a negative cell surface marker to isolate prospectively the epidermal stem/progenitor cells from cultured human keratinocytes. She was awarded an MRC Career Development Fellowship for Stem Cell Research in 2003. In 2004 she moved to the Tumour Biology Centre, Cancer Research UK Clinical Centre, Queen Mary’s School of Medicine and Dentistry at Barts and The London to start her MRC fellowship and began her independent research career since then. In 2007 she cloned the human Dsg3 cDNA that led to the discovery of a novel function of this gene in epithelial cells. Over the years she has published a series of first- and last-authored papers in high profile journals, including JCI, JCS, Stem Cells, ECR and PloS ONE.

Publications:

Key Publications

Tanima Mannan, Sara Heidari Foroushania, Farida Fortune and Hong Wan. RNAi mediated inhibition of the desmosomal cadherin, desmoglein 3, impaired epithelial cell proliferation. Cell proliferation. 2011 In press

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. 2011 Jan;40(1):67-76. doi: 10.1111/j.1600-0714.2010.00951.x. Epub 2010 Oct 4.

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. 2010 Dec 3;5(12):e14211.

Gemenetzidis E, Elena-Costea D, Parkinson EK, Waseem A, Wan H, Teh MT. Induction of human epithelial stem/progenitor expansion by FOXM1. Cancer Res. 2010 Nov 15;70(22):9515-26. Epub 2010 Nov 9. Erratum in: Cancer Res. 2011 Jan 1;71(1):290.

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. 2010 Jul;341(1):121-9. Epub 2010 Jun 4.

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. 2009;4(3):e4849. Epub 2009 Mar 16.

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 2007 May;25(5):1286-97. Epub 2007 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 2007 Jan 30.

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 2004, 150(5), 878-891.

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 2003 Oct 15;116(Pt 20):4239-48. Epub 2003 Sep 2.

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. MacGRath. Lack of plakophilin 1 increases keratinocyte migration and reduces desmosome stability. J Cell Sci Aug 15;116(Pt 16):3303-14. Epub 2003 Jul 2.

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. 2003 Aug;12(4):378-88.

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. 2002 May;118(5):838-44.

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. 2002 Feb;118(2):232-8.

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. 2001 Jul;7(7):801-6.

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. 2001 Feb;31(2):279-94.

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. 2000 May;30(5):685-98.

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. 2000 Jun;15(6):1058-68.

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. J Clinical Invest, 1999 Jul;104(1):123-33.

Research interests:

Dr Wan’s interests are on desmosomes and their role in associated diseases. Desmosomes are molecular complexes of adhesion structure and anchor the cell surface adhesion proteins to the intracellular intermediate filaments. These structures are abundant in epithelial tissues including skin and oral mucosa that experience extensive mechanical stress. Defects in the genes encoding desmosomal proteins, or disruption of desmosome adhesion by autoimmune antibodies and/or bacterial toxins, result in clinical diseases mainly involving the skin, oral mucosa and heart. Increasing evidence suggests that desmosomal proteins have broader functions than simply joining the epithelial cells together and play a role in the regulation of signalling pathways that are involved in cell adhesion, differentiation, morphology and motility. Understanding these additional roles will be of great value for clinical diagnosis and treatment of diseases. Currently, Dr Wan’s team focus on the function of the desmosomal cadherin, Desmoglein 3 in epithelial cells. As this protein has an important role in the pathophysiology of pemphigus vulgaris, an autoimmune blistering disease, as well as in cancer, her team also aim to study the function of Desmoglein 3 in these pathological conditions. Using a combination of cell and molecular biological study approaches, they are trying to elucidate how Desmoglein 3 involves in the regulation of cell adhesion, morphology and differentiation in epithelia.