The ECRT aims to facilitate particularly early career scientists to form small teams to develop their ideas into research projects. The ECRT provides the Einstein Kickbox which offers seed money to carry out initial experiments to validate the novel research ideas, and collaboration support for their team work. The ECRT also offers research and consumable grants to further develop the concept projects into fully-fledged research.
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Urinary stem cells as biomarkers for kidney damage and endogenous repair capacities
Our project aim to establish urinary stem cells as a biomarker for the prediction of renal recovery in patients suffering from acute kidney injury (AKI). AKI is one of the most frequent causes of renal function. While some of the patients show at least some degree of recovery, up to 30% show a permanent loss of their renal function. Presently the driving force of recovery is unknown. We hypothesize that the cell composition in urine mimics the structural damage and regenerative potency of the injured organ and predict that increased amounts of kidney - detached stem cells in urine herald recovery, while their absence indicate permanent damage. The correlation of the total number of renal stem cells in the urine will not only help to predict renal recovery, it will additionally allow direct monitoring of renal regeneration and thus, provide a surrogate marker for clinical studies.
Funding Scheme: Einstein Kickbox & ECRT Research Grant (jointly fundet by the BSRT and ECRT)
Creating a nephro-vascular unit ex-vivo from human pluripotent stem cells
Our project deals with fostering human pluripotent stem cell (hPSC)-derived renal organoids into mini-kidneys. We are trying to encourage intercellular interactions, growth and morphogenesis within the organoid by providing the chorio-allantoic membrane (CAM) of chick embryos as a vascular niche for ectopic organogenesis. This experiment will help us estimate the degree of maturation of the organoid into an organ upon introduction of oxygen supply and shear flow. The results of this experiment will be used to tailor a 3D-printed, chip-based perfusion system to mimic the nephro-vascular unit that developed from a fetal to an adult stage on the CAM. This chip design will be realized using flexible funds and can be used as an ex-vivo culture system for healthy and patient-derived induced kidney cells.
Team : Krithika Hariharan, Su-Jun Oh, Andreas Kurtz
Funding Scheme: Einstein Kickbox & ECRT Reserach Grant
An hiPSC-derived Thyroid-Follicle-Model for Basic and Translational Science
The thyroid is one of the most affected organs when it comes endocrine pathologies. It is a perfectly build reactor-like system within our body to deliver the needed amounts of thyroid hormone to regulate fetal development or e.g. energy metabolism later in life. Thyroid hormone synthesis happens in a tightly regulated and well-balanced system with feedback inhibition and crosstalk to various other hormonal systems.
To test scientific paradigms and hypothesis, there are limited options especially in the field of in vitro test systems. The structure of the thyroid gland, and especially its substructure unit, the follicle, can’t be copied by a simple monolayer cell culture, as its function prerequisites a lumen, surrounded by a monolayer of specialized cells, the thyrocytes. Just within this lumen, our organism is able to synthesize thyroid hormone.
Therefore novel 3D cell culture models are needed.
The aim of our project is to generate a human 3D organoid model that replicates the tissue architecture including follicles of the thyroid. We will use human induced pluripotent stem cells (hiPSC) to differentiate towards thyroid. To archive this we will utilize factors and manipulate signaling pathways known to play a role in thyroid development in the embryo. These factors will be used for screening e.g. their dosage, combination, sequential application and application time to drive the hiPSC towards thyroid.
Team: Valeria Vallone, Kostja Renko, Harald Stachelscheid, Özlem Vural, Roland Lauster, Manfred Gossen
Funding Scheme: Kickbox
Alterations in TGF-ß storage in fibroblastic extracellular matrix: a consequence of inflammation and impaired BMP signaling?
Team: Susanne Hildebrandt, Petra Knaus, Peter Fratzl, Christian Hiepen, K Blank
Funding Scheme: Einstein Kickbox - ECRT Research Grant
Fibroblast - the unsung heroes
The therapeutic potential of mesenchymal stromal cells is being explored in a wide variety of fields. However, MSCs are not capable to always lead to a tissue reconstitution and the mechanism behind the potential is still poorly understood or even questioned. The question whether stem cell therapy can help patients with heart failure is controversially discussed and recently led to a consensus paper that states that bone marrow stem cells are not suitable to regenerate heart muscle cells and that instead a very low percentage of new cardiomyocytes could be regenerated by supporting mitosis. These observations make a re-evaluation of the cascades of endogenous healing or the lack thereof (and the generation of fibrosis) even more relevant. To enable regeneration of tissues, that otherwise lead to scar formation, different approaches are needed to enhance endogenous healing. To this respect an understanding of the cellular composition and the potential of these cells, as well as their interplay with each other and the extracellular matrix, appears eminent – and would be the research perspective of the here proposed project.
Team: Claudia Schlundt, Christian Bucher, Kathraina Schmidt-Bleek, Sophie Van Linthout, Georg Duda, Carsten Tschöpe, Kathleen Pappritz
Funding Scheme: Einstein Kickbox Advanced Scientsits & ECRT Research Grant
Understanding the perfect ECM-network - assure cardiac function, permit regeneration
Team: Juliane Münch, Salim Seyfried, H Moghtadaei, Sigmar Stricker, Ulf Landmesser, Phiipp Jakob, Peter Fratzl, H Simon
Funding Scheme: Einstein Kickbox & ECRT Reserach Grant
Designing novel drugs for balancing the inflammatory phase - A mathematical approach
Recent research has shown, that a balance between suppression of inflammation and hyper-inflammation is crucial for regeneration and wound healing. Inflammation is often accompanied with tissue acidosis. This results in a different chemical environment of the pathogene (low pH) versus the healthy tissue (normal pH). We develop a novel method to keep the inflammation balanced by drug therapy. For this purpose, a drug is needed which has an activity controlled by the chemical environment. In this context an efficient drug to shape the inflammatory phase should act in hyper-inflamed regions and be almost inactive in low inflammatory parts.
In cooperation with Charité we already developed a selective opioid which only acts in inflamed tissue. The corresponding mathematical models and tools will be transferred to the regenerative therapy context. For understanding how to shape the inflammatory phase of regeneration we employ mathematical modeling. Our methods allow for modeling molecular systems in balance can map the relevant processes in dependence of the inflammatory state.
Team: Marcus Weber, Konstantin Fackeldey, Christoff Schütte
Funding Scheme: Einstein Kickbox & ECRT Research Grant