Dr.Caroline Asselman

 Characterization of RNF213 in antimicrobial defense and Moyamoya disease progression 
(promotor Prof. Bart Dermaut) 

This research dives into a fascinating biological "double agent" called RNF213. It turns out this single gene plays a major role in two very different areas: how our body fights off germs (immunity) and a rare brain blood vessel disease called Moyamoya disease (MMD).

Part 1: RNF213 is a "Sensor" for Germs

Scientists already knew RNF213 was linked to MMD, but this study discovered exactly how it helps our immune system fight infections.

• The Tracking Device: RNF213 acts like a heat-seeking missile. It looks for a specific "tag" (a protein called ISG15) that the body sticks onto invading bacteria and viruses.
• The Battlefield: It specifically hangs out on "lipid droplets" (tiny fat bubbles inside your cells) to organize its attack.
• The Enemies: The study showed that RNF213 helps defend against several nasty bugs, including Listeria (food poisoning), Herpes (HSV-1), and certain respiratory viruses.
• The Backup Plan: When RNF213 is missing, the cell tries to compensate by pumping out more Nitric Oxide—a chemical "bleach" that kills bacteria—to keep the infection at bay.

Part 2: Solving the Mystery of Moyamoya Disease (MMD)

MMD is a condition where the main arteries in the brain slowly narrow and block up. While we know genetics are involved, it’s not the whole story.

Diverse Genetics

In East Asia, one specific mutation in RNF213 is the main cause. However, this study looked at patients in Northern Europe and found that the causes are much more diverse. Some had RNF213 mutations, but others had different genetic issues entirely (like Trisomy 21).

The "Second Hit" Theory

Just having the "bad" gene isn't always enough to get sick. The researchers believe an immune trigger (like a past infection or inflammation) might be the "second hit" that actually starts the disease in people who are already genetically at risk.

What’s happening inside the arteries?

The study found that the smooth muscle cells in the brain's blood vessels "rebel." Instead of staying flexible and helping blood flow, they transform into a different type of cell that builds up "gunk" (extra-cellular matrix), which eventually plugs the artery.

• Inflammation: They found immune cells (macrophages and lymphocytes) inside the blocked areas, proving that the immune system is actively involved in the damage.
• A Potential Test: They found a specific protein in the blood (cellular fibronectin) that could potentially be used as a simple blood test (biomarker) to help diagnose MMD.

Why This Matters

By understanding that RNF213 is both an immune protector and a vessel regulator, doctors can start looking for treatments that address both sides of the coin. This could lead to better ways to catch MMD early and perhaps even stop the blockage before it causes a stroke.