Supervisor View Full Details

• genetics, genomics and molecular biology
• cancer/oncology
• epidemiology/population health research

• Medicine
• Surgery
• Pathology

• Oncology

The Glynn lab focuses on understanding inflammation related mechanisms and how they contribute to the initiation and progression of breast and prostate cancer contributing to poor patient outcomes. The lab has three main focuses of interest.
1. Nitrosative stress due to inducible nitric oxide synthase overexpression and its consequences for poor outcome in triple negative breast cancer.
2. The role of human endogenous retrovirus K in breast and prostate carcinogenesis.
3. The interactions between mesenchymal stem cells and prostate cancer cells during bone metastasis and their impact on metastatic progression and the development of therapeutic resistance.

Examples of Glynn Lab publications:
1. Prueitt R*, Wallace TA*, Glynn SA*, et al. An immune-inflammation gene expression signature in prostate tumors of smokers. Cancer Res. 2016 Mar 1;76(5):1055-65. *Joint first author
2. Wallace TA, Downey R, et al, Glynn SA. Elevated HERV-K mRNA expression in PBMC is associated with a prostate cancer diagnosis particularly in older men and smokers. Carcinogenesis 2014 May 23. pii: bgu114.
3. Toner AP, McLaughlin F, et al, Glynn SA. EL102, a novel microtubule inhibitor with pre-clinical activity against prostate cancer. Br J Cancer 2013 Oct 15;109(8):2131-41.
4. Glynn SA, Boersma BJ, et al (2010) . NOS2 predicts survival in estrogen receptor-negative breast cancer and is associated with a prognostic basal-like transcription pattern. J Clinical Investigation, 120, 3843-54.
5. Glynn SA, Boersma BJ, et al (2009) A mitochondrial targeting sequence polymorphism in the MnSOD gene predicts inferior survival in breast cancer patients treated with cyclophosphamide. Clinical Cancer Research, 15(12) 4165-73.
6. Glynn SA, Gammell P, et al. (2004) A new superinvasive in vitro phenotype induced by selection of human breast carcinoma cells with the chemotherapeutic drugs paclitaxel and doxorubicin. Br J Cancer, 91, 1800-1807.

The Prostate Cancer - Bone Marrow Mesenchymal Stem Cells Para-endocrine Axis in the metastatic tumor microenvironment
Mesenchymal stem cells (MSC) are multipotent stem cells that can differentiate into osteoblasts, chondrocytes, adipocytes, myocytes and neurons. They can be sourced from the bone marrow (BM) stroma, adipose tissue and dental pulp, and are also found in circulation and are known to home to inflammatory sites. Due to their capacity to home to injured tissue, research has suggested a reparative function for MSC in multiple tissues. In recent studies it has been shown that MSC can also home to tumour sites and contribute to tumour growth and progression. MSC have been shown to increase the metastatic potential of tumour cells by promoting their migration and invasion as well as having a role in the development of a metastatic niche at the secondary site. BM-MSC may also contribute to tumour growth by differentiating into cancer associated fibroblasts (CAFs), which form part of the tumour microenvironment. Additionally BM-MSCs are intrinsically radio- and chemo-resistant due to a heightened DNA damage response, and thus may contribute to treatment resistance. Our preliminary studies demonstrate that considerable baseline variations exist in the secretomes of primary BM-MSCs which impact the magnitude of their response to prostate cancer cell lines, and vice versa. This indicates that inter-patient BM-MSC variation, may impact on tumour microenvironment dynamics, influencing a patients risk of metastasis, and potentially therapeutic response.
Project Aims
1. Investigate the mechanisms by which MSCs increase prostate cancer invasive and migratory capacity
2. Decipher the opposing roles of androgen receptor signalling in MSCs and prostate cancer 3D co-cultures and what this may mean for anti-androgen therapies in the metastatic setting
3. Determine the mechanism of enhanced IDO1 induction in patient derived MSCs compared to healthy donor MSCs and if this increases their immunomodulatory capacity.