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Full NameDr Paul B Mullan
Department:Centre for Cancer Research and Cell Biology
Organisation:Queen's University Belfast
- genetics, genomics and molecular biology
Liquid Biopsies, Drug development
My group have long standing interests in investigating the mechanisms driving the pathogenesis of breast cancers. We have also a strong involvement in the early diagnosis of ovarian cancer using blood samples.
(1) For breast cancers we are particularly interested in Triple Negative Breast Cancers (TNBCs) and other subgroups of breast cancers with particularly poor outcomes, such as those with amplified T-box2 (TBX2). Our investigations have found that aberrant TGF beta signalling drives TNBC growth and spread, with a transcription factor called GLI2 playing a major role. In TBX2-amplified breast cancers, we have found that the enzyme Lysine Specific Demethylase 1 (LSD1) is important in helping TBX2 switch off important growth control genes, making LSD1 an attractive treatment possibility.
(2) For ovarian cancers we know that many regions of cellular DNA becomes aberrantly methylated as the disease progresses. We have identified a number of these regions and we show that they are consistently altered, even in early disease when compared to matched normal tissue. When we extract small amounts of circulating tumour DNA from patients' blood we can detect these changes also, meaning that we now have the basis of a diagnostic test to detect ovarian cancef earlier and more accurately.
(1) Breast Cancer: A potential project area would involve the development of a prognostic marker of poor outcome for TNBC. Unfortunately, at present there is no way to predict which TNBC patients will relapse. Using the information we have already generated from our studies of TGF beta/GLI2 biology, we would trial markers regulated by this pathway using TNBC samples, possibly through immunohistochemistry of tissue microarrays.
(2) Ovarian Cancer: The student would be involved in helping to develop a blood test based on the aberrant methylation events which occur in ovarian cancer. This is an exciting area of translational research for our group and the use of 'liquid biopsies' as a relatively non-invasive approach for early detection and/or diagnosis is being tested in many cancer types. Two clinican PhDs have previously optimised many of the workflows. The student would be involved in testing markers (individually, or in combination, through PCR-based techniques using patient and volunteer samples) to see which marker(s) show the greatest diagnostic potential.