Dr Hong Wan, PhD
Email: email@example.comTelephone: +44 20 7882 7139Room Number: Blizard Building
Dr Wan was qualified as a dentist in West China School of Stomatology in 1983. After eight years working in clinic, Dr Wan moved to research and obtained her PhD in 1995 at The Faculty of Medicine, University of Liverpool. Her first postdoctoral post (funded by Wellcome Trust) was based 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 epithelia. In 1999, she joined a team at St John's Institute of Dermatology, St Thomas' Hospital in London, working on hereditary skin disorder caused by mutations in the genes encoding the desmosomal proteins, 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 (Dsg3) as a negative marker to isolate 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, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, to start her MRC fellowship and began her independent research since then. In 2007, she successfully cloned the full length human Dsg3 cDNA into a retroviral vector that led to the discovery of novel signalling roles of Dsg3, that have important implications in cancer progression.
Dr Wan's research interest is on intercellular junctions including desmosomes in health and associated diseases. Currently her team is focused on the novel signalling role of the desmosomal cadherin, desmogelin 3 (Dsg3) in cancer progression and metastasis as well as in pemphigus vulgaris, a life-threatening autoimmune blistering disease.
Desmosomes are molecular complexes of adhesion structures and anchor the cell surface adhesion proteins to the intermediate filament cytoskeleton. These structures are abundant in epithelial tissues, such as skin and oral mucosa that experience extensive mechanical stress. Defects in the genes encoding desmosomal proteins, or disruption of desmosome adhesion by autoimmune antibodies or bacterial toxins result in various diseases with clinical manifestation of blistering in the skin and the oral mucosa, as well as the heart in some cases. Increasing evidence suggests that desmosomal proteins have broader functions than simply mechanically attaching cells together and mediate intracellular signalling transductions that regulate diverse cellular responses, such as cell adhesion, proliferation, differentiation, polarisation, morphology and motility. In addition, desmosomal proteins are found to be associated with other junctional proteins and to coordinate with them in the control of various cellular processes. Thus understanding of these additional roles will not only advance our knowledge of the pathophysiology of associated diseases but also will be of great value for clinical diagnosis and treatment of the diseases.
Using a combination of cellular and molecular biological study approaches, Dr Wan's team is trying to elucidate how Dsg3 is engaged in the processes of cell adhesion, differentiation, morphogenesis, and cell migration. Since Dsg3 has been proposed to play an important role in tumour progression and metastasis in head and neck cancer as well as in blister formation in pemphigus vulgaris, her team aims to characterise the molecular mechanisms by which Dsg3 regulates cell migration and invasion as well as cell-cell adhesion in these pathological conditions.
Brown L, Waseem A, Cruz IN, Szary J, Gunic E, Mannan T, Unadkat M, Yang M, Valderrama F, O Toole EA, Wan H. Desmoglein 3 promotes cancer cell migration and invasion by regulating activator protein 1 and protein kinase C-dependent-Ezrin activation. Oncogene. 2013 Jun 10. doi: 10.1038/onc.2013.186. [Epub ahead of print] PMID:23752190. [PubMed - as supplied by publisher]
Siu Man Tsang, Louise Brown, Hanan Gadmor, Luke Gammon, Farida Fortune, Ann Wheeler and Hong Wan. Desmoglein 3 acting as an upstream regulator of Rho GTPases, Rac-1/Cdc42 in the regulation of actin organisation and dynamics. Exp Cell Res. 2012 Nov 1;318(18):2269-83. Epub 2012 Jul 13.
Tsang SM, Brown L, Lin K, Liu L, Piper K, O'Toole EA, Grose R, Hart IR, Garrod DR, Fortune F, Wan H. 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. 2012 Jan 4. doi: 10.1002/path.3982. [Epub ahead of print]
Tanima Mannan, Sara Heidari Foroushania, Farida Fortune and Hong Wan. RNAi mediated inhibition of the desmosomal cadherin, desmoglein 3, impaired epithelial cell proliferation. Cell Prolif. 2011 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. 2011 Jan;40(1):67-76. 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.
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 3-dim cells in primary and immortalized keratinocyte lines. Stem Cells 2007 May;25(5):1286-97. Epub 2007 Jan 25.
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.
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. Disruption of epithelial tight junctions by house dust mite faecal pellet proteinase. J Clinical Invest, 1999 Jul;104(1):123-33.