Dr Nikolaos Georgopoulos

I did my BSc in Biochemistry & Genetics (1994-1997) and my PhD (1997-2001) in the Department of Biochemistry and Molecular Biology at the University of Leeds. I then worked as a post-doctoral research fellow firstly at the Cancer research UK Clinical centre, St James's Hospital in Leeds (2001-2005) and then at the Jack Birch Unit of Molecular Carcinogenesis, Department of Biology, University of York (2005-2008).

I am interested in understanding the molecular aetiology of epithelial cancer development (activation of oncogenes, loss of tumour suppressor function, constitutive induction of cell proliferation and attenuation of pro-apoptotic pathways) and how the process of carcinogenesis itself affects the way epithelial cells respond to the immune system and its products, particularly in the context of proliferation, differentiation and apoptosis (cell death).

2012

Rubenwolf, P., Georgopoulos, N., Kirkwood, L., Baker, S. and Southgate, J. (2012) ‘Aquaporin Expression Contributes to Human Transurothelial Permeability In Vitro and Is Modulated by NaCl ’ PLoS ONE , 7 (9), p. e45339. ISSN 1932-6203

2011

Georgopoulos, N., Kirkwood, L., Varley, C., Maclaine, N., Aziz, N. and Southgate, J. (2011) ‘Immortalisation of Normal Human Urothelial Cells Compromises Differentiation Capacity.’ European urology , 60 (1), pp. 141-149. ISSN 1873-7560

2010

Georgopoulos, N., Kirkwood, L., Walker, D. and Southgate, J. (2010) ‘Differential Regulation of Growth-Promoting Signalling Pathways by E-Cadherin’ PLoS ONE , 5 (10), p. e13621. ISSN 1932-6203

Walker, D., Georgopoulos, N. and Southgate, J. (2010) ‘Anti-social cells: Predicting the influence of E-cadherin loss on the growth of epithelial cell populations’ Journal of Theoretical Biology , 262 (3), pp. 425-440. ISSN 0022-5193

2009

Rubenwolf, P., Georgopoulos, N., Clements, L., Feather, S., Holland, P., Thomas, D. and Southgate, J. (2009) ‘Expression and Localisation of Aquaporin Water Channels in Human Urothelium In Situ and In Vitro’ European Urology , 56 (6), pp. 1013-1024. ISSN 0302-2838

Chopra, B., Georgopoulos, N., Nicholl, A., Hinley, J., Oleksiewicz, M. and Southgate, J. (2009) ‘Structurally diverse peroxisome proliferator-activated receptor agonists induce apoptosis in human uro-epithelial cells by a receptor-independent mechanism involving store-operated calcium channels’ Cell Proliferation , 42 (5), pp. 688-700. ISSN 0960-7722

2008

Walker, D., Georgopoulos, N. and Southgate, J. (2008) ‘From pathway to population - a multiscale model of juxtacrine EGFR-MAPK signalling’ BMC Systems Biology , 2 (1), p. 102. ISSN 1752-0509

Hill, K., Errington, F., Steele, L., Merrick, A., Morgan, R., Selby, P., Georgopoulos, N., O'Donnell, D. and Melcher, A. (2008) ‘OK432-Activated Human Dendritic Cells Kill Tumor Cells via CD40/CD40 Ligand Interactions’ Journal of Immunology , 181, pp. 3108-3115. ISSN 0022-1767

2007

Kottke, T., Sanchez-Perez, L., Melcher, A., Vile, R., Diaz, R., Thompson, J., Chong, H., Harrington, K., Calderwood, S., Pulido, J., Georgopoulos, N. and Selby, P. (2007) ‘Induction of hsp70-Mediated Th17 Autoimmunity Can Be Exploited as Immunotherapy for Metastatic Prostate Cancer’ Cancer Research , 67 (24), pp. 11970-11979. ISSN 00085472

Georgopoulos, N., Merrick, A., Scott, N., Selby, P., Melcher, A. and Trejdosiewicz, L. (2007) ‘CD40-mediated death and cytokine secretion in colorectal cancer: A potential target for inflammatory tumour cell killing’ International Journal of Cancer , 121 (6), pp. 1373-1381. ISSN 00207136

2006

Crallan, R., Georgopoulos, N. and Southgate, J. (2006) ‘Experimental models of human bladder carcinogenesis’ Carcinogenesis , 27 (3), pp. 374-381. ISSN 0143-3334

Georgopoulos, N., Steele, L., Thomson, M., Selby, P., Southgate, J. and Trejdosiewicz, L. (2006) ‘A novel mechanism of CD40-induced apoptosis of carcinoma cells involving TRAF3 and JNK/AP-1 activation’ Cell Death and Differentiation , 13 (10), pp. 1789-1801. ISSN 1350-9047

Steele, L., Georgopoulos, N., Southgate, J., Selby, P. and Trejdosiewicz, L. (2006) ‘Differential susceptibility to TRAIL of normal versus malignant human urothelial cells’ Cell Death and Differentiation , 13 (9), pp. 1564-1576. ISSN 1350-9047

2005

Shaw, N., Georgopoulos, N., Southgate, J. and Trejdosiewicz, L. (2005) ‘Effects of loss of p53 and p16 function on life span and survival of human urothelial cells’ International Journal of Cancer , 116 (4), pp. 634-639. ISSN 0020-7136

2002

Bugajska, U., Georgopoulos, N., Southgate, J., Johnson, P., Graber, P., Gordon, J., Selby, P. and Trejdosiewicz, L. (2002) ‘The Effects of Malignant Transformation on Susceptibility of Human Urothelial Cells to CD40-Mediated Apoptosis’ Journal of the National Cancer Institute , 94 (18), pp. 1381-1395. ISSN 1460-2105

Stockwin, L., Matzow, T., Georgopoulos, N., Stanbridge, L., Jones, S., Martin, I., Blair-Zajdel, M. and Blair, G. (2002) ‘Engineered expression of the Coxsackie B and adenovirus receptor (CAR) in human dendritic cells enhances recombinant adenovirus-mediated gene transfer’ Journal of Immunological Methods , 259 (1-2), pp. 205-215. ISSN 0022-1759

2000

Georgopoulos, N., Proffitt, J. and Blair, G. (2000) ‘Transcriptional regulation of the major histocompatibility complex (MHC) class I heavy chain, TAP1 and LMP2 genes by the human papillomavirus (HPV) type 6b, 16 and 18 E7 oncoproteins’ Oncogene , 19 (42), pp. 4930-1935. ISSN 0950-9232

General areas of interest and projects

The aim of our research is to understand how the process of malignant transformation regulates epithelial cell fate. In particular, we want to determine how genetic alterations implicated in carcinogenesis influence proliferation/growth, molecular and functional cyto-differentiation as well as epithelial cell responses to pro-apoptotic signals, particularly those triggered by members of the TNF Receptor (TNFR) family of proteins. For our studies, we use epithelial cell culture models with direct physiological relevance, such as urothelial (bladder), colorectal (gut) and epidermal (skin) cells.

PhD positions

Prospective students who have government sponsorships/scholarships are very welcome to apply for PhD or MRes positions (please send informal enquiries by e-mail).

Positions are available in the following areas of research:

1. Cell death (apoptosis)/autophagy pathways:

Members of the Tumour Necrosis Factor Receptor (TNFR) family regulate epithelial cell growth/proliferation as well as cell death and autophagy pathways. Our previous work has demonstrated for the first time how members of the TNFR family such as CD40, TRAIL-R, Fas and TNFR-I regulate cell growth versus apoptosis in normal, malignant and ‘para-malignant’ cells with defined genetic alternations. Understanding the precise mechanisms underlying the actions of these receptors will allow the design of novel, tumour-specific anti-cancer therapies.

2. Mechanisms of epithelial carcinogenesis:

Using relevant epithelial cell models, we have previously shown how specific genetic alterations (over-expression of hTERT, inactivation of p53 and p16, constitutive activation of receptor tyrosine kinases, abrogation of E-cadherin function) implicated in cancer alter epithelial life-span, growth, cell adhesion and the response to death signals. Unravelling the influence of these changes in epithelial cell behaviour at the molecular level, and studying the role of signalling pathways such as those triggered by Wnt/beta-catenin and p63 family proteins, will a) help us improve our understanding of the process of carcinogenesis, b) allow better predict disease prognosis and c) may permit the design of tailored, patient-specific therapies.

3. Mechanisms of chemotherapy-induced hair loss:

We have established a collaboration with Paxman Coolers Ltd aiming to develop a deeper understanding of the effect of scalp cooling during anticancer chemotherapy. Although the Paxman cooling cap is often extremely effective at preventing chemotherapy-induced hair loss (alopecia), the success of the treatment often depends on the drug regime being administrated to the patients. Our aim is to use robust and relevant in vitro models to explore, at the cellular and molecular level, the underlying mechanisms of the differences in the responses to cooling, in order to help improve cooling cap efficiency and ultimately patient wellbeing.