Our research focuses on the primary breast tumour microenvironment in the context of cellular interactions, cytokine and exosome secretion, and pathways involved in disease progression. Understanding this environment facilitates harnessing the potential of Mesenchymal Stem Cells as vehicles for targeted delivery of therapy to breast tumours. In Vivo imaging to track MSC migration is an important element of this, and includes novel approaches to imaging and therapy of breast tumours using radiolabelled iodide. The work is multidisciplinary in nature, involving colleagues and collaborators in Surgery, Regenerative Medicine and Physics. We employ In Vitro and In Vivo models of breast cancer in parallel with patient samples, to identify biomarkers of disease, therapeutic targets, and methods to effectively monitor response to therapy. The work is translational in nature, performed by a team of clinicians and scientists. I have successfully mentored a number of clinicians through PhD studies in this programme.
-Joyce DP, Kerin MJ and Dwyer RM. Exosome-encapsulated microRNAs as circulating biomarkers for breast cancer. Int J Cancer (2016) Oct 1;139(7):1443-8. PMID:27170104
-Dwyer RM et al. Mesenchymal Stem Cell mediated delivery of the Sodium Iodide Symporter supports radionuclide imaging and treatment of breast cancer. Stem Cells (2011) 29(7):1149?1157 PMID: 21608083
Through local and international partnerships with colleagues in Surgery, Regenerative Medicine, and Physics, this project will build on our current work harnessing the tumour-targeted migration of Mesenchymal Stem Cells (MSCs) to systemically deliver novel therapies to metastatic breast cancer. The candidate will work with a multidisciplinary team of scientists and clinicians in the Lambe Institute for Translational Research, on the hospital campus at NUI Galway.
The tumour-targeted tropism of MSCs is thought to be due to high local concentrations of inflammatory chemokines and growth factors. This tumour tropism combined with the apparent immunosuppressive characteristics of the cells, has raised tremendous interest in their potential as tumour-targeted delivery vehicles for therapeutic agents. Understanding interactions between MSCs and breast cancer cells will be fundamental to deciphering their potential in this setting. This project will focus on cellular interactions in breast cancer, highlighting the impact of secreted cytokines and exosomes in this crosstalk. Exosomes are tiny vesicles capable of shuttling genetic information including microRNAs, between cells. These short nucleotide sequences are then capable of regulating gene expression in recipient cells. The potential to harness this knowledge for therapeutic intervention, with real time In Vivo imaging of response, will be investigated. Exosomes are also secreted into patient circulation, so an important element of this will be the parallel development of a circulating biomarker to monitor response to therapy, which will be critical for translation to the clinical setting.