A/Prof Michelle Wykes: How understanding of PD-L2 in malaria is helping research into autoimmune disease

Your team is focused on developing novel immunotherapies for autoimmune diseases. What can you tell us about the research to date?

My laboratory was for many years focused on understanding the immunology of malaria. It was through that research that we discovered that a molecule known as programmed cell death 1 ligand 2 (PD-L2) controlled the lethality of malaria. This is a very important molecule as it is associated with PD-1 checkpoint therapy used to treat cancer. This line of research led us to discover a novel immunological molecule, which works with PD-L2 to act like a control switch on immunity.

While excess PD-L2 drives pathological inflammation [as shown here in Crohn’s disease], a loss leads to poor immunity against cancer and infectious diseases. We made antibodies to this novel target to “turn on” and “turn off” immune responses. CSL saw potential in what we had developed, and are working with us to develop a therapy to disrupt the interaction with PD-L2 for rare autoimmune conditions such as lupus, Sjögren’s syndrome and dermatomyositis.

Is the target the same across conditions such as lupus, Sjogren’s and dermatomyositis?

Yes. Our novel target is applicable to initiating immune responses and so is applicable to multiple immunological diseases. We are only just starting, but the switch is the same for multiple immune mediated-diseases.

What aspect of this research excites you the most?

Knowing that many years of basic research has application in curing disease. The value of basic research is very often under-appreciated, but being able to take the findings of my basic malaria research and translate it into a therapy is very exciting.

What have you previously discovered in this area?

I am new to this particular area of research. While that has brought its challenges, it also means that I bring fresh perspectives and experiences of what I have learned in other diseases.

What are the main research challenges?

As all medical researchers know, the funding environment is our biggest challenge – in particular, attracting funding for truly new and innovative research. I am fortunate enough to work for QIMR Berghofer, which, due to the generosity of philanthropic donors, can provide seed funding for innovative projects. This allowed me generate preliminary data to apply successfully for bigger grants.

How long before your work might impact on patient care?

As this is a very new approach, I expect it will be at least a few years.

What’s your Holy Grail – the one thing you’d like to achieve in your research career?

I would like to know that the many years of hard work, grant rejections and personal sacrifices had ultimately improved the quality of life of others. Inflammatory diseases diminish the quality of life of most sufferers with a myriad of symptoms, and to ease this would be an honour.

Who has inspired you in work or life?

My father. He passed away last year in Perth but I could not be with him due to the COVID-19 lockdown. A career in medical research is very demanding and there were times I was tempted to give up, but he always reminded me that being a scientist is a privilege not to be wasted.

How do you achieve work-life balance?

I wish I could say I had achieved a work-life balance…spending time with my now-adult son enriches my life.


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