The Dimmer Sitch: How an Ilongga scientist is helping rewrite the future of diabetic kidney disease

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By Francis Allan L. Angelo

Yvonne Zhang was four years old when she watched the 1995 film Outbreak with her mother and became fascinated with something most children would not have noticed: the positive-pressure personal protective equipment the characters were wearing and the scenes inside a biosafety level 4 laboratory.

Three decades later, the Ilongga scientist — who once commuted daily from Iloilo City to the University of the Philippines Visayas campus in Miag-ao and later put herself through a master’s program at Monash University in Melbourne while working part-time just to cover rent — is part of a research team that has discovered how to essentially turn down the genetic welcome mat for kidney inflammation in diabetic patients.

The discovery, published on February 18, 2026, in the Complications section of Diabetes, the journal of the American Diabetes Association, is titled “Epigenetic Regulation of VCAM-1 by Lipoxin A4 Is Renoprotective Against Diabetic Kidney Disease.” It reveals a previously unknown molecular mechanism by which a natural substance the body produces, called Lipoxin A4 (LXA4), can protect diabetic kidneys by silencing a key inflammation gene through epigenetic modification rather than the conventional inflammatory pathway most researchers expected.

Zhang is among the paper’s 20 co-authors, alongside lead author Madhura Bose, Muthukumar Mohan, Jun Okabe, Harikrishnan Kaipananickal, Victoria Priori, Carolyn Chhor, Karly C. Sourris, Ramtin Radman, Christos Tikellis, Assam El-Osta, Eoin Brennan, Patrick J. Guiry, Kevin Gahan, Catherine Tighe, Merlin Thomas, Karin Jandeleit-Dahm, Catherine Godson, corresponding author Phillip Kantharidis, and Mark E. Cooper.

It is the kind of finding that could eventually change how diabetic kidney disease is treated worldwide — and it came, in part, from a relentless curiosity fostered in Western Visayas.

From Manila traffic to Miag-ao

Zhang was born and raised in Manila before moving to Iloilo in her teens when her mother had to help look after aging grandparents. Science, she said, was introduced to her before she even started school — though she did not take a serious interest in it until high school.

“As a child, whenever we’re stuck in the middle of Manila traffic or waiting for food on our table, my dad would ask me questions such as ‘where does the sun rise?’ or explain to me how laundry soap is made. It’s little things like this that eventually sparked my interest for science,” Zhang said.

Her father, a chemical engineer who has worked across various industries, would conduct mini experiments with her at home — making wine from pineapples and then explaining the scientific principles behind the fermentation, or breaking down how the internet works while they sat in front of a computer. Her mother, a retired nurse, would pull out her college nursing book whenever Zhang was sick as a child, diagnosing and managing her while talking about her experiences working in hospitals and communities.

Zhang completed her Bachelor’s degree in Public Health at the University of the Philippines Visayas. She did not plan to study there — the campus was in Miag-ao and she was living in the city.

“I wanted to go back to living in Manila but my parents wanted me to focus with my studies rather than waste my time in Manila traffic,” she recalled. “Back then, I would travel every day from Iloilo City to Miag-ao then back. I know I had the option of living in the campus but I just couldn’t imagine living in a place that’s quiet and somewhere I’m unfamiliar with at that time.”

After UP Visayas, she went to West Visayas State University for medical school, choosing it because it was closest to her family. Then, in 2023, she started her Master’s degree in Clinical Research, specializing in Translational Medicine, at Monash University in Australia.

A nobody in Melbourne

Zhang had spent summers in Melbourne since high school, where her father works most of the time. His office was right in front of Monash University, so she was familiar with the environment. She also applied to the University of Melbourne for the same program, but what made her choose Monash was its translational medicine philosophy.

“What made me choose Monash University was their translational medicine philosophy of ‘from bench to bedside.’ It resonated with my goal for research, which is not only to publish but to transform your data or research discovery to something that can be used to treat a patient,” she said.

The personal transition was far harder than the academic one. Zhang did not ask for financial support from her parents. She did not have much savings from working in the Philippines.

“I had to look for jobs to pay for my bills while also studying. The cost of living is so expensive in Melbourne. Whatever I earned from my part-time job was just enough to pay for my rent, utilities, and food. It’s been a period of maturing and going out of my comfort zone,” she said.

Navigating a white, male-dominated biomedical research field compounded the challenge. Zhang said she has experienced bias in both the medical and research fields.

“Sad to say that white males will always be favored in these fields. It’s easier for them to get jobs and get grants/research funding. Every now and then, I also experience racism here in Australia,” she said.

She did not have anyone who opened doors for her. Her parents were in business and engineering, and the family had no connections in her specific career path.

“I don’t have that one person whom I can ask ‘how to be you po?’ Or whom I can ask ‘can you hire me to work in your laboratory?’ Here in Australia, I had to email or approach many supervisors in different universities and research laboratories to ask what their research is about, if they were looking for a student, what their goals were and if that resonates with mine. I was a nobody when I arrived here and I knew I had to work hard for them to know me and allow me to work with them,” Zhang said.

A father’s illness, a daughter’s resolve

What drew Zhang specifically to diabetic kidney disease, rather than the cardiovascular complications that are statistically more common among diabetic patients, was deeply personal.

Her father has been a diabetic patient for many years, with all the complications of the disease. He has been compliant with all his medications. His discipline with food intake, she said, is exemplary — the food he eats every meal is weighed in terms of carbohydrate and protein.

“Despite that and the medications available, his disease progresses and I wanted to change this,” Zhang said. “I believe there are many patients like him who are doing the best that they can and who have excellent doctors treating them but we need more effective and life-changing therapeutic agents and that needs to happen soon.”

She described diabetic kidney disease as more mentally devastating for patients than other complications because the damage progresses over time and patients are aware of it.

“They know that sometime in the future, they’ll end up with end-stage renal disease and would likely need dialysis or kidney transplant,” she said.

Ripping up the welcome mat

Diabetic kidney disease (DKD) is one of the leading causes of kidney failure worldwide. Current treatments can slow the damage but cannot stop or reverse it.

The study examined Lipoxin A4, a natural substance the body produces — essentially a peacemaker molecule that tells inflammation to calm down — along with two lab-made synthetic versions called AT-01-KG and AT-02-CT, which are fourth-generation LXA4 mimetics.

The key target is a protein called VCAM-1, which acts like a welcome mat on kidney blood vessel cells, attracting inflammatory immune cells called macrophages that pile into the kidneys and cause scarring and damage. The lipoxins and their mimetics essentially ripped up that welcome mat — they reduced VCAM-1 in kidney cells, which meant fewer immune cells swarming in and less kidney damage. The team assessed LXA4 and its two mimetics in diabetic ApoE knockout mice, followed by in vitro studies in the main renal cell populations, including podocytes, proximal tubular, mesangial, and glomerular endothelial cells.

The lipoxins attenuated albuminuria, mesangial expansion, and collagen and fibronectin deposition as both a preventive and delayed intervention in experimental diabetic kidney disease.

The most surprising aspect of the discovery was not that the lipoxins worked, but how they worked. It was not through the usual inflammatory pathway, NF-κB, that most researchers expected. Instead, it operated through epigenetics — editing what Zhang’s team describes as the dimmer switch on the VCAM-1 gene by altering chemical tags on DNA packaging proteins, specifically reducing a mark called H3K4 monomethylation. This essentially turned the VCAM-1 gene down.

“Previous studies have shown that lipoxins attenuate NF-κB activity, which is a characteristic of inflammation — the hallmark of diabetic complications. The data shows that lipoxins work but how it does that exactly, what other mechanisms it involves apart from the NF-κB pathway, we don’t have the whole picture just yet,” Zhang explained.

The team tested lipoxins both as a preventive treatment and as an intervention after diabetes was already established. Zhang said the intervention arm is always the more exciting one.

“You’re trying to reverse a damage that’s already there,” she said. “Clinically, most of diabetic patients already have the complications of the disease. More often than not, when you see them in the clinic, they already have diabetic kidney disease in the latter stages and they’re not just aware of it. Hence, with the intervention, what you’re after is the cure — to stop and hopefully even reverse the damage.”

Notably, the lipoxins protected the kidneys without lowering blood sugar or cholesterol in the mice, suggesting that the renoprotective effects may be independent of those metabolic factors.

“It doesn’t really tell us about its efficacy in real life patients. Rather, it tells us more about the mechanisms involved,” Zhang said.

Six years in the making

The research took roughly six years from conception to publication. Zhang was not yet part of the department when it started. The work is deeply collaborative — there is no single component that any team member is specifically assigned to.

“Some days you help with staining, some days doing PCR or bioinformatics, culling the animals, some days analyzing graphs, writing, making figures,” she said. “I think the most technically challenging part, not just specific to this research, is compiling all of the data from the beginning until end of your experiments and interpreting all these and writing it. Sometimes, while writing or compiling your data, you come up with questions that you didn’t think of when you started the project and you’re left with a dilemma of should I do more experiments to address this.”

From mice to humans

The synthetic lipoxin mimetics AT-01-KG and AT-02-CT are already fourth-generation versions of LXA4. The natural substance is produced endogenously in the body but is rapidly degraded and inactivated, which is why synthetic versions were developed. These have already entered human clinical trials, which are ongoing.

But challenges remain. The mimetics are fragile — there is a very short time period between the freezer, thawing, and testing them on cells, as they are easily degraded.

If Zhang could design the next study, the question she would most want to answer is straightforward: does it work in humans?

“What works in the test tube or in mice might not work in humans or could work but to what extent? That we do not know yet,” she said.

On whether lipoxin-based therapies could realistically reach patients in lower-resource settings, where diabetes rates are climbing rapidly across Asia and the developing world, Zhang was hopeful but realistic.

“Hopefully it will reach poorer communities and cost wouldn’t be an issue. We all wish for that. After all, diabetes is the ‘pandemic of the 21st century.’ Millions of people are affected and millions also need the treatment,” she said. “I foresee that initially, it wouldn’t be as accessible but eventually it will be. It’s about demand-supply I believe. Just like ozempic — there’s a huge demand but manufacturers could not keep up with the supply. However, there are now projects that aim to increase the supply of the drug through other modalities such as RNA therapy.”

The path less travelled

Looking back at her journey from Iloilo City to co-authoring a paper in Diabetes, the journal of the American Diabetes Association, Zhang said she is most proud of the hard work and determination she brought to pursuing an unconventional path.

“It’s not your typical career path — for someone who goes through medical school, the common goal is to be a specialist in the clinics. I took the path less travelled and that is research. It’s not that stable as a career, especially back in the Philippines. We don’t have the funding and the facilities for it. Additionally, it’s a male-dominated career! But I’m proud that I didn’t allow that to discourage me. In fact, it made me want it more and work harder for it,” she said.

Her advice for young scientists starting out, especially those from outside the traditional centers of Western research, is both practical and philosophical.

“Continue to be curious, ask questions, and actively seek answers for those questions. Push past your limits and make sure you learn something every day — it doesn’t have to be something big. Don’t get discouraged with negative results. A negative result is still a result after all,” Zhang said. “And remember your goal — research doesn’t end with publishing and showing the world your data. There’s more to it. For me, it’s to develop therapies to help people suffering from diabetic complications. Lastly, as cliché as it sounds, you have to make sure that you enjoy the process of discovery.”

Asked what the discovery means to her beyond the science, Zhang’s answer was brief and unambiguous.

“Beyond the science, it’s about helping the community and helping make a difference in this world. Life is too short and we have to give our best and do our part in contributing something good to our society. Discovery is my legacy to Mother Earth.”

At present, she still dreams of working inside a BSL-4 laboratory. For now, Yvonne Zhang is taking one step at a time.

The full study, “Epigenetic Regulation of VCAM-1 by Lipoxin A4 Is Renoprotective Against Diabetic Kidney Disease,” is available at https://doi.org/10.2337/db25-0970.