An Early-Career Breakthrough in Blood Vessel Biology

Q&A

An Early-Career Breakthrough in Blood Vessel Biology

• September 9, 2025

This is a banner year for MDI Biological Laboratory researcher Yannic Becker, Ph.D. Early this summer, he earned his doctorate from Hannover Medical School, while embedded in the laboratory of MDI Bio Lab President Hermann Haller, M.D., inside the Kathryn W. Davis Center for Regenerative Biology and Aging.

That accomplishment was quickly followed by first-authorship of a groundbreaking, peer-reviewed research publication that identifies the vital role that a molecule called heparanase 2 plays in maintaining the health of our blood vessels - a key to the health of all the organs and tissue the vasculature sustains.

We spoke with him recently about his research and career.

Q: You grew up in the northern Rhine area of Germany and received your undergraduate degree at the University of Münster. What sparked your interest in comparative biology?

Becker: I had a biology teacher in high school who was very strict with us. But that was because she wanted us really to learn a lot. So we had a lot of the basic biological concepts: Evolution, DNA replication, basic techniques of, say, PCR, gel electrophoresis.

And we had a small bio lab where we could actually run the experiments ourselves. Every other month or so, we went there and could do some hands-on stuff, which you cannot do in a normal classroom.

I think that was the point where I really was driven towards thinking I want to do science and study biology. Now that I think about it, she advised us to not study biology and rather go for medicine because of job security. Today I'm glad about the choice I made.

Q: You are first author and the research workhorse behind a paper that identifies for the first time the vital role of a molecule called heparanase 2 in preserving blood vessel health and in restoring health to declining vasculature.

You focused in particular on the molecule's interactions with a brush-like layer of sugar-based carbohydrates, called the glycocalyx - a mashup of Greek and Latin words that roughly means "sweet husk". The glycocalyx coats the interior lining of healthy blood vessels (and other cells too). What made heparanase 2 an interesting research target?

Becker: Nobody knew at the time, really, what this protein heparanase 2 was doing in the blood vessels. Why is it there? It's very likely that it has a function, because we have it, mice have it, zebrafish have it, and it seems to have pretty detrimental effects if you don't have it.

Q: What kind of effects? How is it connected to disease?

Becker: In many vascular diseases - like septic shock, chronic kidney disease, diabetic microangiopathy and macular degeneration - the glycocalyx is basically completely degraded and is associated with the emergence of these illnesses. If we are able to protect this layer, the glycocalyx, or even restore it in these disease states, then this might be a valid therapeutic avenue.

Q: And heparanase 2 can play a protective role?

Becker: We found it does, in the vasculature. When we take it out, we saw that the vascular permeability changes. Because usually our blood vessels are tight. There is no flux of fluid across the vessels. But if we take out heparanase 2, we have an increased flux of molecules and water into surrounding tissues. You can think of it as making the lining of our blood vessels "leaky".

Q: Why is that significant?

Becker: Take proteinuria for instance: It's a kidney condition that allows proteins to pass out of the bloodstream and into our urine. In proteinuria the blood vessels in the kidney are more leaky, so that precious proteins that the body needs to retain for good health end up in the urine and are excreted. This has detrimental consequences for our body, like increased risk of cardiovascular disease, blot clots and other conditions.

And proteinuria is directly correlated with the thickness of this glycocalyx layer in our kidneys. The more glycocalyx you have, the less proteinuria you have. We suggest that heparanase 2 is protecting this layer and maintains the essential barrier function of blood vessels.

Q: You also discovered that heparanase 2 can block a signaling molecule called Vascular Endothelial Growth Factor, or VEGF, from binding with the glycocalyx. Why would blocking growth factors like VEGF be important for human health?

Becker: We know that overproduction of VEGF can drive diseases such as macular degeneration and diabetic retinopathy, by promoting an abnormal growth of fragile, leaky blood vessels in the eye.

And cancers can highjack VEGF pathways to do unwanted things like growing vasculature specifically to sustain a tumor.

Now we see that Heparanase 2 is a naturally occurring VEGF blocker. And it's in the bodies of all vertebrates and some other animals too. We showed that in zebrafish, mouse kidneys and human cell cultures, a heparanase 2 deficiency can lead to the vascular conditions seen in the diseases I mentioned that are associated with too much VEGF.

And when we introduced Hpa2 that we produced ourselves in the lab, the blood vessel systems returned to normal.

Q: That's a powerful finding. What are the potential broader medical implications? There are pharmacological treatments to suppress VEGF pathways out there now, right?

Becker:

The pharmaceutical industry has only begun to scratch the surface of glycobiology, which focuses on these sugar-based molecules. Drug development has been more focused on other therapeutic pathways.

Now with heparanase 2, we have a very good understanding of its protective binding activities. And we can build on this to design similar molecules that mimic that.

The idea is that new classes of drugs can be developed to maintain and improve vascular health while causing fewer side effects than conventional treatments. Hpa2 is a beneficial substance that's already being created by our own physiology, which indicates that treatments modeled on this molecule would likely be well-tolerated.

So it could be a target for pharmaceutical treatments or even used as a pharmaceutical itself.

Q: What are your next research steps?

Becker: We have multiple avenues. On the basic science side, we want to learn what other functions the protein has. We've recently found evidence that it might play a role in regulating metals in our body, like maintaining proper levels of iron­ - iron homeostasis.

On the translational side, applying this discovery to real-world medicine, we want to see if we can use heparanase 2 to treat pathological conditions. Septic shock is particularly promising - it's a fatal disease where we see rapid degradation of the glycocalyx and opening of blood vessels, precisely the conditions we've shown that heparanase 2 can counteract.

Q: Do you expect other scientists now will start work with heparanase 2?

Becker: Yes, interest in the molecule is definitely growing. We were able to build a pipeline to accumulate the (Hpa2) protein and enrich it. We have it now in vials and have already shipped it around the world. We are the only group at the moment capable of generating this protein in a reasonable amount and quality.

Q: Why do you want to continue to work with it, rather than move on to new areas of basic research?

Becker: I definitely like this division of starting with a basic, fundamental finding and being able to develop it further and translate it into a useful application. I decided to stay with this project as a postdoc because there's so much to do. I don't want to just let this go in a publication. We should use the momentum we have and try to push it further.