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Anomalies in the formation of blood and lymphatic vessels are, thankfully, rare. Those who do have them face a lifetime of complications that can range from the mild to the life-threatening. To date, little is known about the causes, which means the diagnostic and treatment options are very limited. René Hägerling of the BIH Center for Regenerative Therapies (BCRT) has made it his mission to remedy this. His good ideas have won the regard of the European Research Council (ERC), which has awarded Hägerling, who leads a junior research group, an ERC Starting Grant of €1.5 million over five years.
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.
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About the Berlin Institute of Health at Charité (BIH)
The mission of the Berlin Institute of Health at Charité (BIH) is medical translation: transferring biomedical research findings into novel approaches to personalized prediction, prevention, diagnostics and therapies and, conversely, using clinical observations to develop new research ideas. The aim is to deliver relevant medical benefits to patients and the population at large. As the translational research unit within Charité, the BIH is also committed to establishing a comprehensive translational ecosystem – one that places emphasis on a system-wide understanding of health and disease and that promotes change in the biomedical translational research culture. The BIH was founded in 2013 and is funded 90 percent by the Federal Ministry of Education and Research (BMBF) and 10 percent by the State of Berlin. The founding institutions, Charité – Universitätsmedizin Berlin and the Max Delbrück Center, were independent member entities within the BIH until 2020. Since 2021 the BIH has been integrated into Charité as its so-called third pillar. The Max Delbrück Center is now the Privileged Partner of the BIH.
Contact
Dr. Stefanie Seltmann
Head of Communications & Marketing
Berlin Institute of Health at Charité (BIH)
+49 (0)30 450 543019
stefanie.seltmann@bih-charite.de
www.bihealth.org
https://www.bihealth.org/en/notices/wenn-lymph-und-blutgefaesse-unkontrolliert-w...
Dr. Dr. René Hägerling
David Ausserhofer
BIH/David Ausserhofer
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Dr. Dr. René Hägerling
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