“Our neurogenetics legacy continues, but we’ve also made room for new directions”

Under the joint leadership of Rosa Rademakers and Renzo Mancuso, the VIB-UAntwerp Center for Molecular Neurology is evolving. Long known for its pioneering work in neurogenetics, the center is now expanding into neuroimmunology, recruiting top international talent and investing in collaborative science to tackle the central nervous system’s biggest challenges.

Redefined along two axes

The VIB Center for Molecular Neurology (CMN) in Antwerp has always been a leader in neurogenetics. Thanks to decades of rigorous work under the leadership of Christine Van Broeckhoven, the center earned its place on the international map, spearheading genetic discoveries in dementia and other neurological diseases. This legacy laid the groundwork for a new chapter: one of expansion, reinvention, and a broadening scientific lens.

Since taking on the role of director in 2019, Rosa Rademakers has led the center through a deliberate process of repositioning CMN along two complementary axes: neurogenetics and neuroimmunology.

“The foundation was strong, and we’ve been fortunate to build on it,” she says. “Christine’s work established CMN as a powerhouse in neurogenetics. That legacy continues, but we’ve also made room for new directions.”

In recent years, CMN has recruited a new generation of group leaders with expertise in computational neuroscience, microglia, T-cell biology, and gut-brain immune interactions. Several of them have already secured internationally competitive grants (including ERC awards for Renzo Mancuso and Emanuela Pasciuto, and an Odysseus grant for Seppe De Schepper) underscoring the strength and international standing of the team. 

“We had candidates applying from some of the best neuroimmune labs in the world,” says Renzo Mancuso. “That tells you that the center is being seen internationally not just as strong in genetics, but as a place where cutting-edge neuroimmune research can thrive.”

Shared leadership

Renzo’s appointment as Deputy Director of the Center for Molecular Neurology in January 2024 marked a natural evolution of a partnership already deeply embedded in the center’s day-to-day life. “From early on, I consulted Renzo when making strategic decisions,” Rosa recalls. “He became someone I could count on. Someone who stepped up when the need arose.”

That shared leadership model is no accident. Rosa’s management style emphasizes collaboration from the start, creating a space where people are expected and empowered to contribute beyond the boundaries of their own research. “That was a big part of what attracted me to CMN,” Renzo says. “To help build this community. Rosa and I clicked early on, and over time she entrusted me with more and more responsibilities.”

The leadership structure at CMN reflects the pair’s complementary strengths. Rosa guides the scientific direction and university relations, while Renzo focuses on technology development, infrastructure, and industry collaborations. “There was already strong investment in genetic technologies,” Renzo explains, “but we were lacking some of the tools needed to study function—cellular and mechanistic biology. That’s where I’ve been concentrating my efforts.”

Their co-leadership approach also mirrors the broader structure of VIB itself, which is headed by Christine Durinx as General Manager, focusing on science, and Jérôme Van Biervliet, who leads on translation and innovation. This model of dual leadership rooted in expertise and mutual trust sets the tone for how CMN is run.

“We work in a very horizontal way,” says Renzo. “We share the weight of decision-making. That culture of openness and equality is what makes CMN special.” ​
​Rosa agrees:

“Principal investigators are treated as equal stakeholders. When we bring in new PIs, we tell them clearly: ‘You’re not just here to build your lab. You’re here to help build the center.’ And they take that responsibility seriously.”

But collaboration at CMN extends beyond governance. The Center has invested heavily in inter-lab synergy, creating joint PhD positions that link neurogenetics and neuroimmunology labs. “We now have several PhD students co-mentored by two PIs,” Rosa says. “They sit in on both lab meetings, they share data, and they act as bridges between the two.”

Investing in technology

To further support its dual focus, CMN has built an infrastructure that reflects both its legacy in genetics and its expansion into immunology and functional biology. 

Renzo: “When I joined, there was already significant investment in technologies that supported neurogenetics. However, there was a gap in technologies that supported neuroimmunology and other functional biology aspects. That’s where I’ve been focusing, to help bridge that gap. My background in tech transfer and experience with industry collaborations has been useful in this regard.”

Over the last few years, the center has established several expertise units. According to Rosa, this should help align resources more efficiently and facilitate the collaboration between neurogenetics and neuroimmunology.

The efforts also culminated in the launch of a Tech Satellite in Antwerp, offering on-site support in flow cytometry and single-cell omics under the wings of the VIB Single Cell Core and VIB Flow Core. This constellation should further elevate CMN’s capacity. 

“Having local access to core facilities of the VIB Technologies program lowers the barrier for people to try new things; for geneticists to do functional assays, for immunologists to tap into advanced sequencing. That kind of fluidity is what drives innovation.”

Rosa adds, “We’re also unique in that we’ve continued to invest in long-read sequencing and bioinformatics tools to detect structural variation—types of mutations that are often missed but are crucial for understanding disease. The Neuromics facility led by Mojca Strazisar plays a central role, and of course, that kind of expertise continues to be part of our DNA as a center.”

Upgrading the CMN biobank

One of CMN’s most strategic investments has been the reinvigoration of its biobank. With Julie Van Der Zee now formally overseeing its operations, the center has modernized its collection processes, aligned its consent protocols with contemporary standards, and integrated itself as a decentralized hub within the University of Antwerp biobank.

“We’ve made sure that samples collected now can be used in collaborative research, including with industry,” Rosa says. “That means better compliance, better access, and ultimately better science.”

CMN is currently putting renewed efforts into longitudinal cohorts, including for healthy elderly participants. This group is especially important when we are looking into early diagnosis of age-related diseases, she says. “Initiatives like the Healthy Aging Study led by Kristel Sleegers are vital resources in this regard. We’ve given it a new boost and are actively recruiting and collecting novel types of biospecimens. And we’re making these collections more usable through proper consent and infrastructure.”

In addition, the deep expertise in different CMN groups has culminated in unique disease-focused cohorts across epilepsy, FTD, ALS, Alzheimer’s, and peripheral neuropathies. “Few places in the world have this breadth of neurological disease cohorts,” Rosa notes. While not all of these cohorts are formally embedded within the biobank, there are other ways to tap into these rich repositories, for example through a formal collaboration.

Future plans include establishing induced pluripotent stem cell (iPSC) libraries linked to existing cohorts, making CMN a destination for translational research based on patient-derived material.

“We want CMN to be the place where high-quality biosamples come in, and where real insights come out,” says Rosa.

From genes to function

While CMN’s neurogenetics legacy is rooted in gene discovery, its future lies in understanding what those genes do—and how they interact in complex networks. “We’re moving beyond the monogenic disease model,” Rosa explains. “We’re asking: What are the modifiers? Why do some people with a mutation get sick and others don’t? What are the other factors at play?”

This shift demands new statistical tools, experimental models, and tighter integration between genetics and cellular biology. CMN’s neurogenetics teams are already moving in that direction, each bringing unique disease expertise to the table. The Rademakers lab focuses on frontotemporal dementia, the Sleegers lab on Alzheimer’s disease and healthy aging, the Jordanova team on inherited neuropathies, and the Weckhuysen group on rare epilepsies. Together, they form a robust network tackling diverse neurogenetic disorders—now with increasing emphasis on mechanisms, modifiers, and function.

“There’s a major shift in genetics toward finding functional variants,” Rosa explains. “You might do a GWAS and find a region, but it includes many inherited variants. The challenge is figuring out which one is actually doing something—what’s the causal variant, what’s the mechanism, and how can we model it in a way that leads to therapy?”

To answer those questions, CMN researchers are combining multi-omics strategies with targeted functional assays. “That’s where the work of Valeriya Malysheva comes in,” Rosa adds. “She and her team bring a computational and statistically sophisticated approach to identifying what’s truly causal in the data. It’s a different lens than what we’ve used in the past, and it’s one we need going forward.”

“You can’t model that kind of complexity with a single knockout mouse,” Renzo adds. “You need multi-layered systems, CRISPR tools, and collaboration between people with different types of expertise.”

The same holds true in neuroimmunology, where the field is perhaps already saturated with multi-omics characterizations, he says: “We know what the immune landscape looks like. Now we need to understand better what happens at a functional level: how cells interact, what they do during disease, and how to target them.”

With labs focusing on both the innate (Mancuso lab) and adaptive (Pasciuto lab) immune components in the brain, and on all the peripheral interactions that come with (De Schepper lab), CMN is now well-equipped to tackle these questions.

“Our neuroimmune teams cover all the angles,” says Renzo. “And with the genetics teams moving toward function, we’re aligned in a way that’s really exciting.”

A time for optimism

“We want to give our new labs time to grow,” says Rosa. “That’s how you build a real reputation: when papers start coming out of Antwerp with big findings in both neurogenetics and neuroimmunology.”

The ultimate goal is to translate research into real-world impact, whether through biomarkers, therapies, or other innovations that benefit patients. Despite the complexities and disappointments in neurodegeneration research, both Rosa and Renzo are emphatic: this is not the time for cynicism.

“For the first time ever, we have drugs that can at least partially slow Alzheimer’s disease,” says Renzo. “Instead of seeing that as a breakthrough, the conversation has turned skeptical. I don’t understand it. Ten years ago, such pessimism may have been warranted—we didn’t know where to go. But now, we’re starting to make real progress. This should be a moment to feel optimistic, to feel motivated. There’s still a lot of room for improvement, yes, but that’s exactly why this is the time to push forward.”

Rosa agrees. “That’s just on the Alzheimer’s front. If you look at rare diseases, we’re also seeing incredible momentum: progranulin-based therapies, gene-targeted approaches for epilepsy and peripheral neuropathies, and of course, the antisense oligonucleotides (ASOs) success in spinal muscular atrophy. That was such a boost for the entire field.”

Renzo adds: “The results in spinal muscular atrophy paved the way. Today, ASO-based therapies for SOD1-ALS are already available under compassionate use, and several other experimental treatments are advancing into late-stage clinical trials."

"Today is an incredibly exciting time to be in neuroscience. We’re beginning to break through long-standing barriers, and for the first time, there’s real light on the other side.”

It’s a landscape that would have been hard to imagine even a decade ago. And for CMN, it’s the perfect moment to double down on its vision.

“We’re finally seeing the field move from discovery to therapy,” says Rosa. “And it’s not a handful of pharma companies driving this either. Hundreds of labs, including ours, have spent years laying the groundwork for this new generation of potential treatments.”

Both Renzo and Rosa are confident that CMN is ready to play a key role in what comes next.

“We’ve got the people, the tools, the vision, the culture,” they say. “And above all, the drive to make a difference in this space.”