Julia Montelin Powers
Current PhD StudentDeveloping a Mitochondrial DNA Platform for Prognostic Skin Cancer Biomarkers
Skin cancer brought on by exposure to ultraviolet radiation in sunlight is the most frequently diagnosed malignant neoplasm among Caucasian populations. Diagnoses are increasing in occurrence annually; consequently, a suite of tests to determine an individual’s risk before onset would be of great benefit. Damage to mitochondrial DNA (mtDNA) not only persists but accumulates as sun exposure increases, because mtDNA copy number per cell is sufficiently high to obviate repair. Consequently, the solar radiation-linked deletion of 4977 base pairs of mtDNA (mtDNA4977) has been quantified in the sun and non-sun exposed skin of five cohorts of patients and expressed as a percentage of mtDNA genomes affected, with a second sun exposure linked deletion (mtDNA3895) treated likewise, and found indicative of sun exposure.
Four patients had to be withdrawn from the study due to high deletion percentages; they were on similar prescription medications that may have worked together with sun exposure to produce extensive damage.
Also, chronically sun exposed skin demonstrates altered expression levels of genes when compared to non-sun exposed skin, and in individuals diagnosed with a non-melanoma skin cancer (NMSC), both sun exposed skin and skin peripheral to a lesion show different expression of these genes. Specifically, the gene for manganese superoxide dismutase, a protein responsible for the first step in the removal of the eponymous reactive oxygen species, is significantly down regulated in sun exposed skin of patients with high sun exposure lifestyles, and is indicative of skin cancer risk. Polymerase gamma, responsible for mtDNA synthesis and repair, also shows a trend towards down regulation in high sun exposure lifestyle patients sun exposed skin and may also be a risk indicator.
Additionally, it was discovered that gene expression in proximity to a squamous cell carcinoma was influenced by the tumour environment even though cells were histologically normal.
• Invited contributor: Article on The Science of Summer, Irish Independent newspaper, June 2015.
• Mitochondrial DNA deletion percentage in sun exposed and non sun exposed skin,
Journal of Photochemistry and Photobiology B: Biology, Volume 165, December 2016, Pages 277-282.
• Polypharmacy and sun exposure: Implications for mitochondrial DNA deletions in skin, Journal of Photochemistry and Photobiology B: Biology, Volume 173, August 2017, Pages 397-403.
• Poster presentation and invited speaker: Research and Education Foundation Conference, November 2013.
|Science / Life Sciences||PhD||N/A|
Irish Research Council, Embark Initiative
Dr. James Murphy.