Supervisor View Full Details 2nd

• genetics, genomics and molecular biology
• cancer/oncology

• Medicine
• Surgery
• Pathology

• Clinical Trials
• Endocrinology
• Immunology
• Oncology

The main focus of our laboratory work is to validate cancer biomarkers. Current projects include validation of OncoMasTR panel of biomarkers set in three cancer types:
a. Breast Cancer
b. Malignant Melanoma
c. Prostate Cancer

The workflow includes commercial antibody validation, staining of tissue microarray by immunohistochemistry (IHC) followed by the use of digital pathology for quantification of protein expression by IHC. Digital pathology encompasses the use of image analysis algorithms on digital images created by scanning of the glass slides. Data generated by the image analysis is then combined with patient data to identify if high/low expression of a marker is related to survival.
Suitable commercial antibodies are subjected to a very stringent validation workflow generated in our laboratory. We use commercially available CRISPR/Cas 9 gene-edited knockout cell lines, overexpression constructs, cell lines with naturally occurring high/low expression of certain proteins as a tool to ensure antibody specificity. For IHC, we use an automated platform (autostainer) for both chromogenic and fluorescence multiplexed staining. A major focus of our work is to use digital pathology and image analysis in tissue biomarker research; this task is being overseen by a dedicated histopathologist in our laboratory.

Breast cancer is the most common cause of cancer-related death for women worldwide. After surgical removal of the tumour, early-stage breast cancer patients are prescribed with chemotherapy depending on the possibility of recurrence of the cancer. However, in most cases, conventional clinico-pathological parameters alone are not enough to confidently predict the likelihood of tumour recurrence. For that reason, many early-stage breast cancer patients receive chemotherapy despite the likelihood of receiving no benefit from same, with consequent negative effects on patient morbidity due to side effects of the therapy and associated anxiety. To address this issue, we have developed a prognostic assay termed OncoMasTR based on a panel of several protein biomarkers, which can successfully distinguish between high risk patients who need to be treated with chemotherapy and low risk patients who do not [1]. The primary aim of this project is to convert this assay into a fluorescence multiplex immunohistochemistry assay format where the OncoMasTR test can be performed on a single tissue section, thereby providing a means by which pathologists can use this assay on limiting biopsy samples. The prognostic value of immune cells in cancer has become well established, including seminal work from the Gallagher laboratory [2]. A secondary aim of this project will be to examine the prognostic value of different subsets of tumour infiltrating immune cells in early stage breast cancer and examine potential complementarity with the OncoMasTR assay via data integration.

1. Lanigan F, Brien GL, Fan Y et al. Delineating transcriptional networks of prognostic gene signatures refines treatment recommendations for lymph node-negative breast cancer patients. FEBS J, 282(18), 3455-3473 (2015).
2. DeNardo DG, Brennan DJ, Rexhepaj E et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov, 1(1), 54-67 (2011).