In recent years, a primary focus of melanoma research has been on how UV (ultraviolet radiation) damage to skin cells, which are called melanocytes, contributes to melanoma formation. But no one has ever asked why this damage isn’t repaired in some melanocytes and leads to cancer.
Mater Research Fellow Professor Brian Gabrielli is on a mission to find out just that.
“Our previous understanding of how melanocytes repair UV damage did not explain how the damage accumulates in most melanomas. This research helps to understand this, and our new understanding may form the basis of fresh hopes to manage melanoma better,” says Professor Gabrielli.
Brian, with the help of his Mater research team, have begun to look at how some skin cells repair themselves better than others.
Their research seeks to answer a question—what is broken in melanomas that allows the damage to accumulate rather than being repaired, and leads to increased levels of mutations? While immunotherapy proves very effective on some melanoma patients, it is the variety of melanoma cell mutations that makes it ineffective for all.
“Melanoma is such a unique disease in that it has an extremely high level of mutations, mostly caused by UV exposure. The only type of cancer with similar levels of mutations is lung cancer, though the mutations are caused by airborne carcinogens,’ says Professor Gabrielli.
Having recently been accepted into a peer reviewed journal, Molecular Oncology, Professor Gabrielli’s research has identified a normal repair system that is responsible for the repair of this UV damage in melanocytes. These systems are commonly broken or missing in melanomas which have a lot of UV mutations. This amplified understanding of how melanocytes repair UV damage may eventually lead to new therapeutic targets, or identify individuals who are susceptible to melanomas through a defect in one of the components of the repair system.
“This is about getting the foundations of knowledge—why do some people have more melanoma mutations than others? Quite frankly, we just don’t this know yet.”
Professor Gabrielli’s work directly impacts, and is impacted by, the work of Mater’s Smiling for Smiddy. He hopes is that this initial research will provide the means for new ways to manage how we combat, treat and prevent melanomas in the future.
“We have taken this idea and asked ‘what are the components involved in this normal repair systems, and do defects in these contribute to accumulation of mutations in melanoma?’ But the real question remains to be answered—if the cells are broken, can they be repaired, or can we use this defect to selectively destroy these melanomas?”
Professor Brian Gabrielli is a Professional Research Fellow at Mater and the Head of Mater’s Smiling for Smiddy Cell Cycle Research Group. He participated in the 2018 and 2019 Bottlemart Smiddy Challenge.