Department of Pathology

Professor Nick Coleman

Research description

The W12 cell line system is an accurate model of progression from low-grade pre-cancer (A) to squamous cell carcinoma (B).

Our group aims to translate basic scientific advances into improved cancer diagnostics. We work in two main areas:

  1. Development and evaluation of novel markers for improved cancer screening
    Early detection of cancer by screening will remain one of the most effective (and cost-effective) methods for improving cancer survival in the short- and medium-term. We have shown that minichromosome maintenance (MCM) proteins can substantially improve the early diagnosis of several common cancers, by acting as markers of the ectopic cell cycle entry that characterises malignancy and pre-malignancy. We now aim to drive MCM testing into clinical practice, with emphasis on the following applications:
    1. An 'immunoenhanced' Papanicolaou cervical smear test, which substantially improves the sensitivity and specificity of disease detection.
    2. Stool-based population screening for colorectal cancer. We have recently developed a new method for retrieving colonocytes from stool that provides a greater than thirty fold increase over previous cell yield, without increasing levels of background faecal debris.
    3. High-throughput automated screening of sputum samples in at risk populations. This approach would not be possible using the current cytological test, which is consultant-led and expensive.
    4. Screening for squamous neoplasia in the mouth and anus, both of which represent major health problems in at risk groups.
  2. Mechanisms of cervical neoplastic progression
    We are addressing the contribution to cervical neoplastic progression of variables relating to high risk human papillomavirus (HRHPV) infection, using clinical samples and the unique W12 cell line model system. Questions of particular interest are:
    1. Do specific genetic and/or epigenetic abnormalities underlie deregulation of HPV oncogene expression during cervical neoplastic progression?
    2. Does the contribution of steroid hormones to cervical carcinogenesis depend on HRHPV physical state and/or integration site?
    3. Does HRHPV down-regulate cellular anti-viral receptors in order to promote persistence?
    4. Does HRHPV-induced insertional mutagenesis contribute to clonal selection during neoplastic progression?