Fighting Against Fibrosis

Rebekka Schneider-Kramann's research is a constant battle – against fibrosis. This is what the Professor of Cell Biology at RWTH Aachen University and Director of the Institute of Cell and Tumor Biology at Uniklinik RWTH Aachen calls it when she describes her goals. Schneider-Kramann wants to fight fibrosis in the bone marrow with her successful research proposal “Re-windMF”. The 42-year-old is now being funded by the European Research Council with an ERC Consolidator Grant – one of the most valuable awards available in the European science system.

Thanks to the funding, Schneider and her team at the “Schneider Lab” now have the opportunity to use innovative methods to find ways of preventing fibrosis from spreading unrestrictedly and, even more importantly, to develop therapeutic approaches that can be used to reverse it. Fibrosis is the term used by doctors to describe the massive scarring of organs. It was previously thought that scarring in organs could not be reversed.

The problem: Fibrosis gradually leads to the loss of organ function, and it is therefore very harmful to human health. Fibrosis is particularly dangerous in the bone marrow. It occurs there as a result of blood cancer and it replaces normal blood formation. Instead of new blood, only scar tissue is produced. Hematopoiesis is in turn shifted to the spleen, which quickly becomes too large as a result. The disease therefore ends fatally in a short amount of time. “Unfortunately, patients often only notice fibrosis once the disease has progressed. Our dream is to treat fibrosis in such a way that it regresses and patients no longer need a bone marrow transplant,” she said.

Post-Doc Period at Harvard Medical School in Boston

With a Consolidator Grant, the European Research Council supports scientists in their research work. To be eligible for funding, the research topic must be groundbreaking, ambitious, and feasible. Professor Schneider is now being funded with almost two million euros for a period of five years. This is the second time that she has received ERC funding. She had previously succeeded in acquiring an ERC Starting Grant and had already been awarded an ERC Proof-of-Concept grant.

She has been interested in her research topic for a long time: After studying medicine in Aachen, Rebekka Schneider began working intensively on bone marrow during her specialist training in pathology. Her first major research question was which cells in the bone marrow are responsible for fibrosis formation. “That was always the key issue: If we know about these cells, then we can also try to treat them,” explains the physician.

During her post-doctoral period with Benjamin L. Ebert at Harvard Medical School in Boston, USA, she focused on blood cells. However, in a side project, she identified the so-called Gli1+ cells as being those that are largely responsible for fibrosis in the bone marrow. In order to better understand these cells with new technologies and to investigate how they interact with blood cancer, she applied for and received an ERC Starting Grant from the Erasmus Medical Center Rotterdam in 2017.

The funding gave her the opportunity to establish new methods in mouse blood cancer models as well as in patient samples, which are now crucial for the new research project. It allows her to view the smallest bone marrow biopsies from patients with spatial resolution and thus penetrate down to the cellular level to understand how cancer cells activate the fibrosis-making cells.

This managed to stop fibrosis formation in the mouse model and a clinical trial has now been started based on the results. “The special thing about this time period was that we progressed from classic basic research to a clinical study,” reports Schneider.

The Next Step Towards Treatment

She and her team now want to take the next step with the Consolidator Grant. To go from the Petri dish to the human body, so to speak, and help patients directly with the knowledge that they have acquired. At the moment, fibrosis can only be treated with bone marrow transplantation. However, this therapy cannot be used in many patients because they are already too severely ill for aggressive treatment with high-dose chemotherapy and the administration of donor bone marrow. And even if the treatment is successful, the donated bone marrow may not be able to support the diseased cells in the body.

Schneider and her team want to understand which patients will benefit from a bone marrow transplant. To this end, she will compare many samples in her laboratory, both those in whom the therapy is effective and in whom it is not. She is assisted by the Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation (Medical Clinic IV) at Uniklinik RWTH Aachen, which provides the necessary bone marrow biopsies. These are then analyzed at cell, RNA and protein level with spatial representation and the large amounts of data are then processed bioinformatically, including through the use of artificial intelligence and deep learning in a long-standing collaboration with Professor Ivan Costa and his team. The results are then confirmed in the laboratory in the cell culture dish and in the mouse model. These procedures are always done with the aim of finding new drugs.

This is the only way to identify effective drugs in the end. What’s more: “Without fibrosis, this type of blood cancer can be effectively controlled,” says Schneider. It is also conceivable that a successful form of treatment could then be extended to other types of cancer that are associated with fibrosis.

Rebekka Schneider-Kramann has been recognized for her research with the Gerhard Domagk Prize for Cancer Research (2022), the Swammerdam Award of the Nederlandse Vereniging voor Hematologie (2019), the Artur Pappenheim Prize of the German Society for Hematology and Medical Oncology (2016) and the Innovation Prize of Deutsche Hochschulmedizin (2016), among others. She is part of the founding team of Sequantrix GmbH, which focuses on innovative anti-fibrotic therapies.

– Author: Thorsten Karbach