Charité researchers win six ERC Starting Grants

ERC Starting Grants are among Europe’s highest honors. Once again, six early-career scientists at Charité – Universitätsmedizin Berlin, whose research groups are based at Charité, the Berlin Institute of Health at Charité (BIH), the Max Delbrück Center, and the German Rheumatism Research Center Berlin (DRFZ), have won over the European Research Council (ERC). Their forward-looking projects tackle questions such as how to prevent diseases and how to detect them as early as possible. They also focus on advancing current therapeutic approaches to diseases such as cancer and heart failure. The European Research Council (ERC) will support each of the scientists in building their own research groups to the tune of about €1.5 million over the next five years.

The selected early-career scientists are pursuing visionary ideas that are rooted in basic research. Their projects may involve risk, but they also hold the potential to make major innovative breakthroughs in their fields. “With a total of three Advanced Grants, two Consolidator Grants and seven Starting Grants, Charité has had an outstanding 2022 in terms of ERC funding,” says Prof. Christian Hagemeier, Vice Dean of Research (Preclinical Affairs) at Charité. “This is a tremendous achievement by each of these researchers and a badge of distinction for Charité as a place where groundbreaking research takes place.” 

The new ERC Starting Grants in detail:


What happens when leukemia cells meet immune cells – InteractOmics

Leukemia, a cancer of the blood, occurs when immature immune cells stop developing but keep dividing and eventually inundate the blood. Here, they encounter mature and active immune cells that either recognize and kill the cancer cells or let them escape. The molecular biologist Dr. Simon Haas leads a research group within the joint focus area “Single-Cell Approaches to Personalized Medicine” of the BIH, Charité, and the Max Delbrück Center. He specializes in single-cell analysis and wants to find out why immunotherapies against blood cancers successfully work in some patients but not in others. “We can generate extremely precise snapshots of cellular ecosystems,“ explains Dr. Haas. “We can see which cells are present in a tissue, which cells are active at a given time, how they change, and which proteins they produce. That’s useful if you want to know how many active immune cells are facing how many leukemia cells in the blood.” Dr. Haas and his team plan to advance single-cell analysis so that more light can be shed on the interactions between these cells. Instead of looking at individual cells, they will use samples from leukemia patients to investigate millions of cell pairs. The long-term goal is to further develop immunotherapy so that more patients can be helped.

Learn more about the Haas Group

Diagnosing Vascular Malformations and Individual Treatment – PREVENT

Hereditary malformations of the blood and lymph vessels, so-called vascular malformations, are among the rare diseases. Vascular malformations can occur in all regions of the body and affect the skin, muscles or organs. In some cases, they manifest as smaller blood vessel dilatations; in others, entire extremities or organs may be affected. Some of those affected have no to mild symptoms, in other cases the malformations can lead to life-threatening diseases. Dr. Dr. René Hägerling is a physician and scientist at the Institute of Medical Genetics and Human Genetics at Charité. He heads the Lymphovascular Medicine and Translational 3D Histopathology Department at BIH and is a Fellow of the BIH Charité Clinician Scientist Program. "Knowledge about vascular malformations is very limited, so patients often not given a clear diagnosis or cure despite the severity and progression of the condition," says the physician. "Inspired by precision medicine in oncology, we have designed a patient care concept that offers better treatment based on personalized medicine." Novel 3D histological and molecular genetic methods will help to clarify the cause of the disease in the future. Additional screenings will determine individually which pharmacological therapies are appropriate. Dr. Hägerling's team is convinced that such a concept can also be applied to other rare diseases and improve patient care overall.

Learn more about the Hägerling Group

Crosstalk between stromal and immune cells in the gut – iMOTIONS

Intestinal fibrosis, a hardening of gut tissues caused by an abnormal proliferation of connective tissue, is a frequent and serious complication of chronic inflammatory bowel disease (IBD). There is currently no specific drug that can prevent or reverse such fibrous scarring. Stromal cells, those cells that support and nourish organs like the intestines, play a central role in the development of fibrosis. However, little is known so far about how signals from the immune system control the formation of fibrous connective tissue. Lichtenberg Professor Dr. Dr. Ahmed N. Hegazy is a clinician scientist at Charité’s Department of Gastroenterology, Infectious Diseases and Rheumatology on Campus Benjamin Franklin. He also directs a liaison research group at Charité and the German Rheumatism Research Center Berlin (DRFZ), an institute of the Leibniz Association, which intensively studies inflammatory mechanisms. Prof. Hegazy and his team now want to determine the causes of impaired tissue repair. “Such tissue changes are very common in chronic intestinal inflammation, but the existing anti-inflammatory therapies have little effect on fibrosis,” explains Prof. Hegazy. “We want to find new biomarkers that help identify patients at risk of developing intestinal fibrosis, while also leveraging our discoveries to find therapies that prevent or help treat fibrotic diseases.” His current research is focusing on cytokines, which are signaling molecules produced during an immune response. The aim going forward is to understand the interplay or so-called crosstalk between stromal and immune cells in the intestinal mucosa – in both healthy and inflammatory conditions as well as in abnormal tissue repair.

Learn more about the Hegazy Lab

The neurotransmitter dopamine in human movement – ReinforceBG

More than six million people worldwide suffer from Parkinson’s disease, a neurological disorder associated slowed movements, tremor, muscle stiffness, and gait impairment. Neuroscientist Prof. Wolf-Julian Neumann’s goal is to better understand how these symptoms develop in order to advance new technological therapies. His work focuses on the role of brain networks that are modulated by dopamine, a  neurotransmitter in the brain that is critical to the regulation of animal and human behavior. “We hope to achieve a new, holistic understanding of dopaminergic brain circuits in movement and learning,” explains Prof. Neumann, the project’s leader at Charité’s Department of Neurology and Experimental Neurology. “But our research also has special clinical significance for the treatment of Parkinson’s disease, as it entails a degeneration of precisely those neurons that release dopamine in the brain.” He and his team plan to use brain activity measurements and cutting-edge methods to improve the understanding of the neurotransmitter and its effects. The knowledge gained could contribute to the development of brain stimulation implants and lead to a new generation of brain-computer interfaces. This technology could potentially lead to a functional restoration of the affected brain circuits, with the aim to alleviate patient symptoms. In close collaboration with Charité’s Departments of Neurology and Neurosurgery, Prof. Neumann’s research group is leveraging invasive brain signal recordings and connectomics to gather a better understanding on the development of parkinsonian symptoms.

Learn more about Prof. Wolf-Julian Neumann’s research.

Rewiring cardiac metabolism – KetoCardio

A special form of heart failure known as HFpEF (heart failure with preserved ejection fraction) will likely become the leading cause of heart failure in coming years. In HFpEF, it is not the heart’s pumping power that is impaired, but its ability to relax between beats. As a result, the cardiac muscle cannot take in enough blood to supply the body with sufficient oxygen and nutrients. People with HFpEF experience a reduced exercise tolerance, fluid accumulation in the lungs and the rest of the body, and shortness of breath. Currently, little is known about the molecular mechanisms of the disease and barely any drugs exist to treat it. Dr. Gabriele G. Schiattarella, cardiologist, leads a research group at Charité’s Department of Internal Medicine and Cardiology as well the DZHK-funded guest group “Translational Approaches in Heart Failure and Cardiometabolic Disease” at the Max Delbrück Center. He and his team have discovered that HFpEF patients have elevated levels of ketones in their blood. Ketones are by-products of the body breaking down fat. When our cells do not receive sufficient glucose – during fasting or exercise, for example – the body burns fat instead of glucose. This produces ketones, which function as an alternative source of energy for cells. Dr. Schiattarella wants to investigate what it is that stimulates ketone metabolism in HFpEF and why. He also wants to clarify whether and how ketones, particularly the most common ketone ß-hydroxybutyrate (ß-OHB), regulate processes of the cardiac muscle cells and thus affect such things as the cells’ elasticity. The aim is to gain a deeper understanding of ketone metabolism and signaling to develop novel, effective therapeutic strategies for HFpEF – whether, for example, through diet, exercise training, or drugs.

Learn more about the Schiattarella Group

Preventing intestinal diseases before they develop – REVERT

The stomach and intestines are exposed to a wide variety of external factors. They are therefore lined by a protective cell layer that is continually regenerated: the epithelium. Prof. Michael Sigal is a clinician scientist at the Charité Department of Hepatology and Gastroenterology and at the Max Delbrück Center. He focuses primarily on stem cells, which are responsible for the continuous regeneration of this barrier between the body and the outside world. An Emmy Noether Independent Junior Research Group under his direction is investigating how these stem cells can potentially be damaged, and also how this damage contributes to the development of infectious and inflammatory diseases as well as cancer. So far, the team has demonstrated that an injury of the intestinal mucous membrane can lead to a reorganization of the cellular hierarchy. When stem cells located deep inside the mucous membrane die, they are replaced by fully differentiated cells from the surface. The latter are reprogrammed into stem cells and begin to divide, thus regenerating the mucous membrane. This regeneration process prevents bacteria in the gut from entering the bloodstream after an injury. However, Prof. Sigal hypothesizes that it may also represent the first step in the development of colorectal cancer. “Cells from the surface of the epithelium come into contact with the microbiome – the bacteria that colonize our intestines – and their metabolites, some of which can cause DNA damage. If they become stem cells, mutations can become fixed in the epithelium, disrupting the complex processes that normally ensure an equilibrium between cell division and differentiation – the first step towards the development of cancer.” During the next five years, he hopes to explain what changes take place in the gastrointestinal epithelium in the wake of an injury. This knowledge could serve as a basis for developing therapies that target the underlying causes of inflammatory intestinal diseases and contribute to the prevention of colorectal cancer.

Learn more about Prof. Sigal’s research

 

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