John Doorbar group

This page has been archived; Current information about John Doorbar's research is available from his website at University of Cambridge.

Human papillomavirus biology and disease

Human Papillomaviruses (HPV) cause a range of significant human diseases, including laryngeal papillomatosis, genital warts and cervical neoplasia. Certain HPV types, known as high-risk types, cause cervical lesions that can progress to cancer. Cervical cancer accounts for around 12% of all female cancers worldwide and is almost always caused by high-risk HPV.

Central to understanding papillomavirus-associated disease are model systems, which allow us to examine in the laboratory how the virus disrupts the normal growth and differentiation of the epithelial cells that it infects. Using such approaches, we can study the initial events during lesion formation, the mechanism of disease resolution and viral persistence, and how viral latency and re-activation might be mediated. In our group, such studies are supported by strong links with clinical laboratories, and by appropriate molecular studies which look at viral protein function and the cellular pathways that they disrupt in order to support the normal or de-regulated virus life cycle. Our work is ultimately driven by the need to better understand HPV disease and how to limit its impact.

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A. The E4 protein is cleaved by the protease calpain, which removes sequences from the N-terminus (red) and exposes the C-terminal amyloid fold (purple arrows) to allow E4 multimerisation

B. E4 multimers exist as amyloid fibrils, which can be seen under the electron microscope

C. HPV infection of the cervix leads to cervical neoplasia of different grades. The E4 protein (which is stained in green) assembles into amyloid structures in the upper epithelial layers. The red staining marks cells that are progressing through the cell cycle, while cell nuclei are counter stained blue

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