Meet Simon: uncovering the genetic roots of autoimmune disease for new treatments

For some, the experience of the medical system is a saga. But rather than a tale of adventure and action, it is the infuriatingly cyclical ‘diagnostic odyssey’.

Autoimmune and autoinflammatory diseases are often chronic, recurring and difficult to treat. Estimates suggest around four to five percent of Australians are impacted by these issues. Even relatively common diseases have a diagnostic rate of around 20 per cent.

This means that for many people, getting a clear diagnosis is difficult. They are left bouncing between different specialists, treating symptoms instead of the root causes of their condition – using intense medications like steroids to manage side-effects.

Some conditions are so rare or treatment resistant that even after being diagnosed people are left in limbo after numerous medical interventions.

That’s where Associate Professor Simon Jiang enters the story.

As the group leader of the Personalised Medicine and Autoimmunity (PMA) Laboratory at the Australian National University, Jiang understands the toll this excursion can have on patients.

“In many circumstances, a clear diagnosis can be difficult,” he says.

“Worse, for patients living with autoimmune diseases, treatment side effects can be as bad as the illness itself.”

Jiang’s lab takes a personalised medicine approach – getting to the root cause behind diseases such as systemic lupus erythematosus, inflammatory bowel disease, chronic kidney disease and rheumatoid arthritis. The approach is an Australian-first.

“By understanding an individual’s unique causes of illness, we attempt to provide personalised diagnosis and treatments, potentially leading to better outcomes for each patient,” he explains.

“My clinical expertise in autoimmune disease allows me to bridge the gap between research and patient care, translating our findings into effective treatments for patients.”

Start at the source

Treatment at Jiang’s lab starts with each patient’s DNA. After genome sequencing, Jiang can map genetic level variation to try to discover the source of the genetic variant behind a patient’s disease.

Finding the source can help with diagnosis and, in certain cases, developing potential personalised treatments that treat issues at the genetic level. These therapy treatments have been shown to better target the issue with reduced side effects.  

To date, the Personalised Medicine program at The John Curtin School of Medical Research has sequenced the genomes of more than 1,100 individuals.

They have also uncovered new never-before-seen disease mechanisms from rare gene variants causing lupus, dermatomyositis, and kidney disease.

For Jiang, this is part of the reward itself.

“I find almost every aspect of my work enormously fascinating,” he says.

“On the laboratory side, there is a consistent stream of discovery – new insights into immune function and biological processes, finding new gene variants with surprising consequences.

“On the clinical side, I’m still amazed and excited how we can translate our laboratory discoveries into effective ways to help people with immune diseases directly.”

Guiding people on their medical odyssey toward better health might sound stressful but Jiang says his family, his passion for his work and his connoisseur-like appreciation for good protein bars keep him going.

“I’ve found that balance is important everywhere, and more so the greater the pressures of work,” Jiang says.

“This applies to how you approach problems, deal with adversity, aspire to achieve things and manage yourself and things around you.

“In many ways, it’s best encapsulated by the idea of the ‘golden mean’, which is a surprisingly effective guide for navigating the often-stressful demands of my career.”

For those looking to embark on their own medical research journey his advice is similar – finding your passion will take you far.

“Be motivated by the things that you’re passionate about and stay focused on what you are working towards,” he says.

“If you love what you do, not only will it give you the best chance of work satisfaction, but you will likely excel at it.”

Transformative changes

Teenager Grace Campell came into contact with Jiang and his team at a difficult time in her life.

When she was in Year 8, she started having sudden unexplained problems with her vision. Grace, who was 14 at the time, was worried that whatever was causing her issues could lead to permanent blindness.

“My eyes were playing up in the sense that there were big black dots everywhere,” she says.

“And then it went down a journey of just small immune things like skin issues and whatnot, and a long line of medications.

“There was a long journey of steroids, which I don’t think is ideal for any young girl … I would experience weight gain and intense emotions – very happy or very sad – and have hot flashes.”

While doctors puzzled over what was causing her symptoms, Grace was told not to play sport or do anything that would raise her blood pressure too much. She also had to take time out of school to attend doctors’ appointments and travel to Sydney for fortnightly treatments.

Grace’s mother also saw the emotional impact of the sudden change of being “in a world of medics”.

“She was feeling odd in her own skin,” Her mother explains. “At 14 and 15, it was going to school and going, I feel different. I can’t understand what’s going on.”

“We didn’t want to go, well, this is the drugs we’ve been given, and we’ll sit until we’re told otherwise.”

The family was referred to Jiang’s lab, where Grace felt she was taken seriously.

“It felt much more personalised and much more, ‘we’re actually going to get to the bottom of this for your sake’,” Grace says.

“You didn’t feel like you were coming with a bunch of symptoms. And then, as much as it’s still trying to put the puzzle together, your cause was actually cared for.”

Grace is now feeling “stable” and her parents are pleased with the progress Jiang’s lab has made.

“Simon’s work is actually really targeting the issue and really going into the layers to try to find what the problem is,” her father says.

“We were looking at a lot of unknowns… and the likely outcome was blindness.

“But we are confident with Simon’s work that we are actually on a path that will see her not become blind, and that’s appreciation with a capital A.”