Melanie McConnell

Courses

Teaching in 2018

Personal Bio

PhD University of Otago | BSc (Hons ) University of Otago

After completing a BSc Honours degree in Microbiology at the University of Otago, I moved over to the Biochemistry department of University of Otago for a PhD in the Cancer Genetics laboratory, with Professor Tony Reeve and Dr Michael Eccles.  Four years looking at the intricacies of transcriptional regulation in the pediatric cancer Wilms’ Tumour provoked a life-long interest in cancer cell biology, and in the importance of regulating gene expression correctly.

My post-doctoral research examined aberrant regulation of gene expression in leukemia at Mount Sinai School of Medicine in Manhattan. After a 2 year fellowship in New York stretched into 8 years, I returned to New Zealand in 2006 to establish the Cancer Stem Cell programme at the Malaghan Institute of Medical Research. This focused on the brain tumour glioblastoma, but also included work in melanoma and breast cancer.  In 2013 I joined the School of Biological Sciences, but my team and I continue to work closely with our colleagues at the Malaghan Institute, particularly in the area of gene expression regulation.

Research interests

Cell biology of stress responses

The primary focus of my research is to understand how cancer cells survive stress, and to apply this knowledge to the development of more effective cancer therapies.  Cancer cells have to survive free radicals, lack of oxygen, reduced nutrients, and changes in metabolism. During chemotherapy, immunotherapy and radiation treatment, cancers are subjected to further stress, yet many cells survive and go on to cause relapse and metastasis. Of particular interest currently is the role of mitochondria in therapy resistance – this occasionally overlooked organelle may hold the key to understanding how cancer cells respond to DNA damaging therapies.

My group use various methodologies including primary cell and tumour culture, flow cytometry, qPCR and PCR in situ, RNA-sequencing, chromatin immunoprecipitation, immunofluorescence, confocal and high throughput microscopy to identify DNA damage and stress response pathways that mediate therapy resistance. We are focused on the primary brain cancer glioblastoma, a notoriously therapy-resistant cancer that kills >90% of people within a few years of diagnosis.

The pathways that are utilised by brain cancer cells in responding to stress are the same used in a normal brain cell.  We also look at how understanding, and potential manipulation, of cellular survival pathways, including mitochondrial-mediated processes, can be used to best advantage in diseases where accelerated cell death is a major concern such as neurodegenerative diseases.

Visit the Cell Survival research group

Publications

Connor, L. M., Tang, S. C., Cognard, E., Ochiai, S., Hilligan, K. L., Old, S. I., . . . Ronchese, F. (2017). Th2 responses are primed by skin dendritic cells with distinct transcriptional profiles. Journal of Experimental Medicine, 214(1), 125-142. doi:10.1084/jem.20160470

Berridge, M. V., Schneider, R. T., & McConnell, M. J. (2016). Mitochondrial Transfer from Astrocytes to Neurons following Ischemic Insult: Guilt by Association?. Cell Metabolism, 24(3), 376-378. doi:10.1016/j.cmet.2016.08.023

Grasso, C., Anaka, M., Hofmann, O., Sompallae, R., Broadley, K., Hide, W., . . . McConnell, M. J. (2016). Iterative sorting reveals CD133+ and CD133- melanoma cells as phenotypically distinct populations. BMC Cancer, 16(1). doi:10.1186/s12885-016-2759-2

Berridge, M. V., McConnell, M. J., Grasso, C., Bajzikova, M., Kovarova, J., & Neuzil, J. (2016). Horizontal transfer of mitochondria between mammalian cells: Beyond co-culture approaches. Current Opinion in Genetics and Development, 38, 75-82. doi:10.1016/j.gde.2016.04.003

Jones, N. M., Rowe, M. R., Shepherd, P. R., & McConnell, M. J. (2016). Targeted inhibition of dominant PI3-kinase catalytic isoforms increase expression of stem cell genes in glioblastoma cancer stem cell models. International Journal of Oncology, 49(1), 207-216. doi:10.3892/ijo.2016.3510

View more publications on ResearchGate

Courses

Teaching in 2018