Unravelling the Misinterpreted Protein in Liver Disease
Duke-NUS Assistant Professor Anissa Widjaja’s research redefined the role of IL11 in liver diseases, and now hopes to improve patient care through inhibition of this gene.
Asst Prof Anissa Widjaja focuses her research on the involvement of IL11 in several fibro-inflammatory conditions and targeting IL11 as an effective treatment.
A protein – interleukin-11 (IL11) – that the scientific community had long believed to be the “good guy” that protect livers and other organs, actually has the opposite function.
This discovery by Duke-NUS Medical School’s Assistant Professor Anissa Widjaja and her team is now helping them to develop a novel therapeutic approach to treat diseases.
Over the past seven years, Asst Prof Widjaja focused her research on unraveling the involvement of IL11 in several fibro-inflammatory conditions. She looked at the potential of targeting IL11 as an effective treatment for these conditions, particularly a severe liver disease called non-alcoholic steatohepatitis (NASH).
In previously published literature, it was suggested that IL11 was a protective cytokine: anti-fibrotic, anti-inflammatory, and pro-regenerative, but her team were not convinced by the data as many researchers had exclusively used human IL11 in mouse disease models.
They then used species matched human IL11 on human fibroblasts and mouse IL11 on mouse fibroblasts, and discovered that IL11 is a pro-fibrotic protein, making it damaging to the organ instead.
“By largely misinterpreting results derived from the use of human IL11 in mice, the scientific community had missed the crucial role of IL11 for more than two decades,” said Asst Prof Widjaja.
With this discovery, Asst Prof Widjaja led a recent breakthrough study on a novel antibody-based therapeutic drug that could block the IL11 pathway.
This could effectively reverse all the three major clinical phenotypes observed in NASH patients, including inflammation, scarring, and fat accumulation, while lowering blood glucose and cholesterol levels.
This drug is currently developed for use in clinical studies by Boehringer Ingelheim.
Her team’s discovery on IL11 also prompted them to investigate whether the same observation held true in other organs, most notably in the liver.
They are now investigating whether anti-IL11 therapies can treat and reverse kidney failure by enabling kidney regeneration.
Asst Prof Widjaja (right) and her research team discovered that IL11 is a pro-fibrotic protein, contrary to previous scientific literature.
Embarking on a career in science
Being very curious about the world since young, Asst Prof Widjaja shared that she had always been fascinated with biomedical professions.
“I paid extra attention in biology classes and spent my free time watching medical TV series and scientific documentaries. That led me to apply to the School of Biological Science at Nanyang Technological University (NTU), where I did both my undergraduate and doctoral studies.”
She found her PhD research on the interactions between proteins and how they are regulated scientifically intriguing, but she struggled to see its real-world impact.
She was then determined to find a job where she could conduct research with clear translational applications and has the potential to make an impact in people’s life.
After landing a postdoctoral position at Duke-NUS in 2013, under the mentorship of Professor Stuart Cook who is a world-leading expert in the IL11 field, Asst Prof Widjaja said she “genuinely experienced what it means to make scientific discoveries that have the potential to be further transformed into new treatments”.
“For that reason, I don’t take my job and my work for granted. I wake up each morning feeling thankful that I get to do what I do - something that I truly believe is important and could potentially transform medicine and improve people’s life someday.”