Two labs, one question: MAGISTER begins

Glucocorticoids are the cornerstone treatment for polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), yet a substantial group of patients barely responds to them while still suffering the side effects. That unanswered clinical problem is the starting point of MAGISTER, a new research project led by Prof. Dirk Elewaut (VIB–UGent–UZ Gent) and Prof. Karolien De Bosscher (VIB–UGent). The project was recently selected as the very first laureate of the newly launched Fund Stéphanie Willems, managed by the King Baudouin Foundation. We sat down with the driving forces behind MAGISTER to discuss their ambitions, the urgent medical need behind this work, and the remarkable story of how their long-standing collaboration began.

Congratulations! As the very first laureates of the new Fund Stéphanie Willems, you’re kicking off with MAGISTER, quite a name…

Dirk: A strong project needs a strong name. You have to be able to brand it. It’s an acronym packed with complex terms — Molecular Approach to Glucocorticoid Resistance and Inflammation in Stimulating Timely Management of Rheumatic Diseases PMR and GCA — but it also hints at something ‘magical’. People remember it.

Karolien: We didn’t have to think long about it. It felt right immediately.

With a focus on polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) it fits the call. But I assume this is not the only reason to focus on these diseases?

Dirk: The impulse came directly from the clinic. The advantage of being a physician–scientist is that you can take a clinical frustration and turn it into a research question. Both PMR and GCA are inflammatory rheumatic conditions — one affecting shoulder–hip girdle but can also be associated with arthritis, the other a form of arterial inflammation — yet they remain surprisingly underexplored. PMR is very common, affecting around 1% of people over 50, while GCA, although less frequent, can lead to acute blindness if not treated quickly. Treatment for both ​ relies heavily on glucocorticoids. Some patients respond extremely well; others relapse as soon as we taper, and a substantial subgroup hardly benefits at all. As a clinician, you feel that unmet need every day.

Karolien: And for me, the glucocorticoid receptor has been the red thread throughout my career. Over the years, my perspective broadened to metabolic nuclear receptors and how various nuclear receptor family members interact. The possibility of applying that expertise to a concrete clinical need was immediately appealing.

What do we already know about glucocorticoid-based drugs, and what remains unclear?

Dirk: Glucocorticoids are effective and inexpensive, but they come with well-known side effects, such as hyperglycemia, osteoporosis, and mood swings. When non-responders still experience the side effects but not the benefits, that’s a major therapeutic gap, one we can only address once we understand how resistance arises. A second challenge is the tapering itself. Every four weeks, you lower the dose, and ideally, patients should no longer need medication after about a year. But the timing of relapse is unpredictable. Without deeper biological insight, you’re navigating blindly. That’s why I’m glad we can rely on Karolien and her team to explore this at the molecular level.

Karolien: We want to understand why some patients are glucocorticoid-resistant. Is glucocorticoid receptor signaling already different at baseline? Does the pathway respond differently when treatment starts? Can we recreate a resistant state in vitro? Our multiomics approach lets us examine many layers of the disease at once — from gene activity to protein signaling — so we can uncover differences between responders and non-responders without starting from assumptions. Therefore, we need patient material that captures the full range of responses. ​

Dirk: That’s why we work with both retrospective samples, already available from previously treated patients, and prospective samples, which we will collect and document as new patients enter the clinic.

How do you approach collecting and documenting all these patient samples? That seems like a challenge in itself.

Dirk: It certainly is, and that’s why we’re grateful to rely on Prof. Isabelle Peene and Dr. Ann-Sophie De Craemer (both affiliated with VIB-UGent and UZ Gent), who each bring translational expertise to the project. They coordinate the clinical side of the project. Because Isabelle works in two hospitals, we were able to collect around 100 retrospective samples, enough to draw meaningful conclusions.

Karolien: Those retrospective samples allow us to get started right away. They give us the clear contrasts we need: strong responders and clear non-responders. Even though the material wasn’t originally stored with future molecular analysis in mind, it’s a good foundation for the early lab work. The prospective samples, on the other hand, will give us the detailed clinical follow-up we need to properly interpret the molecular data. Without well-documented patient trajectories, those signatures simply remain abstract patterns.

Dirk: And that’s where things become more complex. PMR and GCA don’t follow a straightforward diagnostic path. Patients enter the system through many different specialties: rheumatology, neurology, internal medicine, ophthalmology… If you want to collect samples in a structured way, everyone needs to be aligned. A clinical care path is essential. And that’s exactly where Ann-Sophie comes in. She coordinates communication across departments, keeps physicians engaged, ensures structured documentation, and makes sure the clinical data will integrate seamlessly with the molecular analyses. She recently secured EULAR funding for training in Groningen, a leading center for clinical care pathways. That expertise will be invaluable.

Karolien: Without that level of coordination, a project like this simply wouldn’t fly. Strong clinical documentation is the backbone. It allows us to understand how the molecular findings relate to real patient behavior. ​

And how does this translate to the work in the lab?

Karolien: In the lab, we’re already moving. Our PhD student, Catharina Van Laetem, initiated the ethical approvals needed to analyze the early samples and will also build the in vitro endothelial model. That model will give us an early platform to test and validate pathways or markers linked to glucocorticoid resistance. ​

Because of the proteomics workflows on scarce material, we are happy Prof. Francis Impens (VIB-UGent), who is part of Catharina’s PhD guidance committee, can share his expertise. The real depth, however, will come once data from the prospective patient samples start coming in. That’s when we can truly connect the molecular findings to what happens in the clinic.

What could this project ultimately change for patients?

Dirk: If we can detect non-responders earlier, we can spare them unnecessary side effects and move to alternative treatments sooner. That alone would be a major step forward.

Karolien: And the insights may extend far beyond PMR and GCA. Glucocorticoid resistance is relevant across a spectrum of inflammatory and autoimmune diseases. If we uncover shared mechanisms, the broader impact could be substantial.

It’s impressive how everything comes together. How did you decide to start this project together?

Karolien: When the call for this new fund appeared, it was Elien Vandermarliere from the VIB Grants team who immediately spotted the fit. She knew we had worked together before and realized how well our expertise aligned, so she brought the pieces together. It made perfect sense to apply as a team.

Dirk: Yes, we really do form a team. There’s trust. We understand each other’s language, and there is complementarity and that makes the work not only smoother but genuinely enjoyable.

With a successful application on top …

Dirk: It was one of the most efficient applications our group has ever done. The momentum was there. Isabelle and I were together at a conference in the US, which meant we had uninterrupted time to focus. And because we were in a different time zone from Karolien, we could literally write in relay. Fast and concentrated, it just flowed.

Karolien: That kind of focus is only possible when you can rely on strong teams who keep everything running. You need to trust that the ship sails on when you step back to isolate yourself and write. And I must say the review process of this new fund was refreshing and constructive. Based on our written application, the international jury sent us questions, which we could address during a presentation. Their feedback was genuinely valuable.

And now you’re ready to collaborate again. Your story together goes quite far back, doesn’t it?

Karolien: (laughs) Yes, it’s a rather unusual story — more than twenty years ago now. The VRT launched a call to highlight local scientific research in a more creative way, and they asked researchers to submit a concept and write an initial script that brought both basic science and clinical expertise together. I really wanted to do it, and because I was working on Compound A at the time — a molecule originally derived from a desert plant — the storyline almost wrote itself. We needed a physician in the script, and Dirk’s expertise made him the obvious choice. We submitted it together, we won, and the episode of Overleven was made: “De woestijn geneest” (The desert cures).

Dirk: Participating ​ in a documentary starting in ​ the desert…, quite a change of scenery. It was a very creative period, and it didn’t stop with the documentary; it turned into a scientific follow-up. We tested the compound in arthritis models ​ and unraveled its unique working mechanism afterwards. Eventually, that path reached its limit, but it sparked successful collaborations and led to two PhD theses.

And now MAGISTER. What keeps you most motivated at the start of this new project?

Dirk: The synergy. We know each other’s strengths, we trust each other, and that makes the work energizing.

Karolien: We’re entering a new disease area together, but the curiosity and trust are the same as twenty years ago. That combination makes us very eager to begin.

Dirk: The clinical pipeline is ready, the lab is ready, and the need is clear. Time to get started.

Thanks, Karolien and Dirk!

Sooike Stoops

 

• sooike.stoops@vib.be