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Centenary Institute - Medical Research
Centenary Institute - Medical Research

Gene discovery may explain female melanoma survival advantage

Centenary Institute scientists have discovered that genes on the X chromosome may be key to the improved survival rates of females with melanoma–as compared to their male counterparts. The findings could ultimately lead to more effective treatments for what is an aggressive and potentially deadly form of skin cancer.

We know that survival from melanoma is strongly related to gender with females having a survival rate almost twice that of males,” said Dr Abdullah Al Emran (pictured), researcher in the Melanoma Oncology and Immunology Program at the Centenary Institute and lead author of the study.

“Many explanations such as behavioural differences in sun exposure and other factors have been previously proposed for this gender difference but none had withstood critical scrutiny. We believed that further examination of the role of the X chromosome was warranted.”

What the researchers explored were a number of genes on the X chromosome–and more specifically those genes that had been found to escape a cellular process called ‘X-inactivation’.

A normal regulatory process in the body, X-inactivation is where one of a female’s two X chromosomes is inactivated or silenced during embryonic development. Only one functional copy of the X chromosome is required in each body cell.

This ‘silencing’ process is not perfect however–between 10-20% of the genes on the silenced X chromosome are still able to be expressed. As a result of this phenomena females have a double expression of many genes involved in immune responses when compared to males.

“Our study found that two of these genes on the X chromosome that manage to escape inactivation–the genes KDM6A and ATRX–were both associated with improved survival rates for women with melanoma. We believe that their high expression levels aid the body’s immune system in helping to fight cancer,” said Dr Emran.

Notably, the researchers were also able to show a clear link of the gene KDM6A to components of the immune system believed to be important in the killing of melanoma. This was particularly so in the production of interferon gamma, a key protein activated by the immune system to help kill cancer cells.

Professor Peter Hersey, Head of the Melanoma Oncology and Immunology Program at the Centenary Institute, together with co-senior study author Dr Jessamy Tiffen, also from the Centenary Institute, believe the research findings are significant in pointing to KDM6A as a major regulator of immune responses. The focus will now be on how KDM6A is regulated.

“We want to fully know how KDM6A is regulating immune responses and boosting the production of interferon gamma. Understanding these processes will potentially allow the translation of this knowledge into more effective treatments for all melanoma patients,” said Professor Hersey.

Read the full media release here.

Publication:

Study of the Female Sex Survival Advantage in Melanoma—A Focus on X-Linked Epigenetic Regulators and Immune Responses in Two Cohorts. https://www.mdpi.com/2072-6694/12/8/2082

International Day of Women and Girls in Science

Highlighting the Centenary Institute’s Dr Jessamy Tiffen.

Dr Jessamy Tiffen, a senior member of the Centenary Institute’s Melanoma Immunology and Oncology Program has some sage advice for aspiring female scientists in advance of this year’s ‘International Day of Women and Girls in Science’.

“A career in science can be exciting and fulfilling and gives you the potential to make a real impact in the world. There will be barriers to overcome but if you have a curiosity about the world we live in and are prepared to work hard, you might just be amazed where your scientific career can take you,” says Jessamy.

‘International Day of Women and Girls in Science’ held on the 11th February each year is part of a United Nations General Assembly resolution officially recognising the critical role that women and girls play in science and technology. The UN hopes to see full and equal access and participation in science, for women and girls across the globe.

Cancer researcher

As a scientist at the Centenary Institute, Jessamy is focused on trying to better understand melanoma, a devastating disease responsible for more than 1,700 deaths each year in Australia. Jessamy seeks to understand why certain melanomas respond to treatment in some individuals while other melanomas do not.

“Melanoma is the most common form of cancer affecting young Australians which is extremely sad but which is also extremely motivating,” she says. “Understanding the mechanics behind melanoma treatment resistance is essential to developing new drugs and finding new cures which will help save lives.”

Jessamy credits some of her early interest in science from her grandfather who was a microbiologist. “We used to talk about his work around the kitchen table and discuss his latest findings (on footrot!) so the importance and need for research and scientists was communicated to me at an extremely early age. His love of science certainly rubbed off on me,” she says.

Teachers as role models

It was at school however where Jessamy really became captivated by science and much of this was due to the teachers that she was fortunate enough to encounter.  

“I had a series of fantastic female science teachers who were extremely passionate about their work and who were absolutely committed to their students. They were all so positive and allowed my curiosity to flourish. They also helped me to believe in myself – to realise that I was good enough to take my science to a higher level and that there would be career opportunities out there for me. Looking back, I realise how essential it was, having such supportive female teachers encouraging me at such a formative stage of my life.”

Challenges

Jessamy notes that there are still challenges to overcome in the higher learning sector, as well as in the workplace, and that gender disparity still remains an issue in the Australian scientific community. Statistics for example show that women comprise more than half of science PhD graduates and early career researchers, but less than a fifth of senior academics in Australian universities and research institutes.[1]

“Unfortunately factors such as stereotyping of women, a lack of flexibility in working arrangements for mothers and a lack of female role models still persists in our industry,” she says. “Many women I talk with have experienced barriers or a lack of fairness at some point in their scientific career.”  

Jessamy however, believes that this situation is improving. “Organisations are slowly getting better at implementing inclusion and gender equity policies, even compared to a decade ago.”

“I’ve benefited greatly in my current role,” she explains. “The Centenary Institute has policies in place allowing part-time work and flexible hours for mothers. I also have access to a research assistant and was awarded a Carers Travel Award that allowed me to attend a major scientific conference with my baby. It’s this type of support that should be available in all organisations.”

Value of Mentors

Working closely with a female mentor has also proved valuable for Jessamy – in supporting her career aspirations as well as in providing perspective on achieving a work-life balance.

“The Centenary Institute is an academic partner of Franklin Women, an organisation supporting women working in health and medical research careers,” she says.

“I was fortunate enough to undertake their mentoring program which linked me up with a brilliant female mentor outside of my workplace and this has been fantastic. I meet with her on a regular basis and we talk about my goals, how I’m doing at work and any issues or problems that I might be encountering generally. My mentor acts as an objective sounding board for me, she provides advice and has become a friend and advocate for me.”

Advice

Final words of advice from Jessamy to any aspiring female scientist out there?

“We need to encourage a new generation of female scientists to help tackle the major challenges of our time, to break-down barriers and to make it to the top,” says Jessamy.

“If you have an interest in science think about embracing it. There are are so many career opportunities out there for skilled and motivated scientists in areas ranging from aerospace, to biotechnology, telecommunications, agriculture and the environment. Believe in yourself and don’t be afraid to get out of your comfort zone. Just go for it and realise that overcoming the challenges makes it all worthwhile.”


[1] Gender Equity, Australian Academy of Science – https://www.science.org.au/supporting-science/genderequity

New strategy to stop melanoma spread

Scientists from the Centenary Institute have developed a new therapeutic strategy that could potentially help the fight against advanced-stage melanoma.

In a study just released, the scientists were able to show that they could effectively reduce the migration and invasive properties of melanoma cells. This was achieved by successfully inhibiting the interaction between two proteins involved in intracellular trafficking (the process by which molecules cross the membranes of living cells).

The research is significant as metastasis–the process by which cancer moves to new areas of the body–is the leading cause of death in melanoma patients.

Published in the highly regarded Journal of Investigative Dermatology, the researchers first found that high expression of the protein melanophilin was indicative of poor prognosis in melanoma patients.

Employing human melanoma cell line models, the researchers were then able to demonstrate a significant reduction in the spread of cancer by blocking the ability of melanophilin to bind with the protein RAB27A (one of the critical regulators of intracellular transport).

“We have known for some time that the proteins melanophilin and RAB27A bind together and that this process could be crucial to help melanoma cells spread around the body,” said lead study author and Centenary Institute PhD researcher (Immune Imaging Program), Mr Dajiang Guo.

“By disrupting the binding of these two proteins with a recently developed blocking compound (BMD-20), we were able to successfully restrict the melanoma cell movement and invasion. What our findings suggest is that the development of new drugs that can specifically target melanophilin-RAB27A interactions are a promising target for advanced melanoma treatment,” he said.

Senior study author Dr Shweta Tikoo also from the Centenary Institute (Immune Imaging Program) notes that there is an unmet need for novel therapeutic strategies which can be developed as a standalone drug or as part of a combination therapeutic regimen in the battle against advanced melanoma.

“Melanoma has one of the highest mortality rates in the western world with the disease accounting for approximately 1,500 deaths in Australia every year. It is also the most common form of cancer affecting young Australians, those individuals aged from 15 to 39 years old,” she says.

Read the full media release here.

Read the publication in the Journal of Investigative Dermatology here.