Professor Chris Paraskeva
Professor of Experimental Oncology
School of Cellular and Molecular Medicine,
University of Bristol, Medical Sciences Building,
Bristol, BS8 1TD
phone: +44 (0)117 33 12072 (internal 12072)
email: c.paraskeva@bristol.ac.uk
group: Cancer Research UK - Colorectal Tumour Biology group
Research interests
Background
Bowel Cancer is the second most common cause of cancer related deaths in the UK and much of the industrialized world. There is epidemiological evidence that about 50-70% of bowel cancers are preventable by dietary intervention. As well as diet being important there is evidence that non steroidal anti-inflammatory drugs (NSAIDs) such aspirin reduce the risk of cancer. The overall aims of my research are to increase our understanding of the Cellular and Molecular Biology of Colorectal Cancer with the aim to develop novel preventative and therapeutic strategies and to develop new biomarkers for the early detection of bowel cancer. For these studies we use a combination of in vitro (human tumour cell cultures) and in vivo (normal and tumour specimens) approaches.
Specific research interests
- Investigating the regulation of cell growth, differentiation and cell death and how this is deregulated during carcinogenesis with particular interests in the genes promoting resistance to apoptosis in cancer cells.
- Investigating the mechanism by which NSAIDs such aspirin and dietary factors reduce the risk of cancer. With particular interest in how tumour promoting prostaglandins, such as PGE2, are upregulated in colon cancers and how these can be targeted for novel therapies and novel biomarkers for the early detection of benign tumours or cancer.
- Investigating the role of the tumour microenvironment in carcinogenesis, malignant progression and the evolution of drug resistant tumour cells. With particular interest in how hypoxia and energy depletion regulate gene expression and function of key genes involved in colorectal cancer such as β-catenin, aiming to exploit the tumor microenvironment for novel cancer prevention and treatment strategies.
- Investigating the regulation and function of intestinal cancer stem cells and whether these stem are the cells which make a tumour resistant to treatment and how these can be targeted for prevention and treatment.
Selected publications
- Smartt, H.J.M., Greenhough, A., Ordonez-Moran, P., Talero, E., Wallam, C.J., Parry, L., Al-Kharusi, M., Roberts, H.R., Mariadason, J.M., Clarke, A.R., Huelsken, J., Williams, A.C. and Paraskeva, C. B-catenin represses expression of the tumour suppressor 15-prostaglandin dehydrogenase in the normal intestinal epithelium and colorectal tumour cells. Gut In Press.
- Roberts, H.R., Smartt, H.J.M., Greenhough, A., Moore, A.E., Williams, A.C. and Paraskeva, C. (2011) Colon tumour cells increase PGE2 by regulating COX-2 and 15-PGDH to promote survival during the microenvironmental stress of glucose deprivation. Carcinogenesis 32(11):1741-1747.
- Greenhough, A., Wallam, C.A., Hicks, D.J., Moorghen, M., Williams, C.C. and Paraskeva, C. (2010) The proapoptotic BH3-only protein Bim is downregulated in a subset of colorectal cancers and is repressed by antiapoptotic COX-2/PGE(2) signalling in colorectal adenoma cells. Oncogene 29, 3398-3410.
- Qualtrough, D., Singh, K., Banu, N., Paraskeva, C. and Pignatelli, M. (2009) The actin-bundling protein fascin is overexpressed in colorectal adenomas and promotes motility in adenoma cells in vitro. Br. J. Cancer 101, 1124-1129.
- Greenhough, A., Smartt, H.J., Moore, A.E., Roberts, H.R., Williams, A.C., Paraskeva, C. and Kaidi, A. (2009) The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 30(3), 377-386.
- Moore, A.E., Greenhough, A., Roberts, H.R., Hicks, D.J., Patsos, H.A., Williams, A.C. and Paraskeva, C. (2009) HGF/Met signaling promotes PGE2 Biogenesis via regulation of COX-2 and 15-PGDH expression in colorectal cancer cells. Carcinogenesis 30, 1796-1804.
- Clemo, N.K., Collard, T.J., Southern, S., Edwards, K.D., Moorghen, M., Packham, G., Hague, A., Paraskeva, C. and Williams, A.C. (2008) BAG-1 is upregulated in colorectal tumour progression and promotes tumour cell survival through increasd NF-kappaB activity. Carcinogenesis 29, 849-857.
- Kaidi, A., Moorghen, M., Williams, A.C. and Paraskeva, C. (2007) Is the downregulation of EphB2 receptor expression during colorectal tumorigenesis due to hypoxia? Gut 56, 1637-1638.
- Qualtrough, D., Kaidi, A., Chell, S., Jabbour, H.N., Williams, A.C. and Paraskeva, C. (2007) Prostaglandin F2 alpha stimulates motility and invasion in colorectal tumour cells. Int. J. Cancer 121, 734-740.
- Kaidi, A., Williams, A.C., and Paraskeva, C. (2007) Interaction between beta-catenin and HIF-1 promotes cellular adaptation to hypoxia. Nat. Cell Biol. 9(2), 210-217.
View all publications held on the University of Bristol's IRIS database