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Dr. René Hägerling, a physician and chemist, researches blood and lymphatic vessels. “I’m interested in how they grow, how they branch, and most importantly why this sometimes goes wrong,” says Hägerling, who researches at the BIH Center for Regenerative Therapies and at the Institute of Medical and Human Genetics at Charité – Universitätsmedizin Berlin. His work aims to help those who suffer from hereditary anomalies in the formation of their blood or lymphatic vessels. Errors in specific genes that affect the vessels’ growth and division cause the vessels to grow unchecked, change their architecture, and sometimes form bulging, liquid-filled lumps in the body or on the skin. “Depending on the extent of the mutation and the affected tissue, the problem can be anything from purely cosmetic to life-threatening,” says Hägerling. “And right now, we can’t do enough to tackle the causes.”

Better diagnostics for better therapy

Because the condition is usually congenital, many of those affected are hospitalized in childhood. “We can sometimes fix the vascular malformations surgically. But when we can’t, we have to resort to powerful growth-inhibiting drugs. And unfortunately, it’s impossible to know in advance if they’ll actually help the patient,” says Hägerling, explaining his motivation.

The first thing Hägerling, who is also a member of the BIH Charité Clinician Scientist Program, has set his sights on is improving diagnostics: “Blood vessels grow in all directions, which means looking at tissue samples using two-dimensional microscopy isn’t enough. That’s why we use light sheet fluorescence microscopy, where the tissue is scanned by an entire plane of light rather than a single beam.” With support from the Berliner Startup Stipendium, the BIH‘s Digital Health Accelerator, and the EXIST Research Transfer funding program from Germany’s economics ministry, Hägerling’s team is developing a workflow that automates the entire process from sample preparation and microscopy to image analysis and diagnosis. For the staining, the team are using nanobodies – antibodies that are coupled with fluorescent dyes and are small enough to easily penetrate tissue.

Combining microscopy and genetics

“We can even combine our image analyses with molecular genetic methods,” says Hägerling. “Our hope is that this will help us discover new genes that are responsible for the vascular malformations. If we’re lucky, some of those genes will be ones we know from other contexts and for which medicines already exist that we could potentially use.” That’s not pie in the sky: Some of the genes involved in vascular malformations are already known from cancer research. “Excessive growth is also the problem in cancer. So substances that block the growth could also help our patients,” says Hägerling.

Unfortunately, though, no one drug exists that helps all patients. And this is precisely the problem that the BIH research group “Lymphovascular Medicine and Translational 3D-Histopathology” is tackling with its new care concept. “We’re inspired by precision medicine in cancer research,” says Hägerling. “We want to provide patients with the exact treatment that will tackle the root of their individual disease. We’re convinced that our concept, which combines precision diagnostics and targeted therapy, can be a model for other rare diseases, such as so-called overgrowth syndromes, and thereby improve care for many of these patients in the medium to long term.”

About the ERC Starting Grant

The ERC Starting Grant awarded to René Hägerling is part of the EU’s Horizon 2020 research and innovation program (PREVENT, grant agreement No. 101078827). The prestigious Starting Grants provide about €1.5 million over five years to early-career scientists and scholars to build their own teams and conduct “high risk, high reward” research. The peer reviewers of the European Research Council (ERC) look for novel approaches that might open up new frontiers and spur significant advances. The researchers must have completed their Ph.D. within the last two to seven years and have a scientific track record showing great promise.

Grant Agreement No. InteractOmics   101078713

Konstanze Pflüger

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