Current Pilot Projects
ELAN-Pilot Projects
ELAN pilot projects provide funds for junior researchers (postdocs, until the age of 39 (i.e. before the 39th birthday) at the time of application).Projects:
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Increasing survival of young cancer patients require fertility-preservation like ovarian-cryopreservation pretherapeutically with retransplantation post-therapy. However, this is not appropriate for all patients due to the risk of relapse. A promising alternative is the artificial ovary: follicles are separated from malignant cells. In the research proposed follicle survival, maturation and growth in 3D-scaffold will be observed by live cell imaging with confocal spinning disc microscopy.
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The focus of the present project is the effect of the human T cell leukemia virus (HTLV-1) on dendritic cells (DCs) in two models. The project focuses on the transmission of HTLV-1 to DCs across an intestinal barrier, analyzing the phenotype of DCs and the mechanism of transmission. For this purpose, two models, a 2D transwell and a 3D organs-on-a-chip model will be established. Finally, both models will be compared regarding their advantages, disadvantages and differences in the DC phenotype.
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Protocols for detection of disseminated cancer cells (DCCs) in the lymph node (LN) need to be harmonized. Therefore, immunocytology vs. conventional ultrastaging will be compared and additional methods for isolation of DCCs for subsequent molecular analysis will be tested. Correlation of morphology with DCC-density and ploidy will be examined. The prognostic impact of the morphology of LN metastases will be investigated in archival cases. Further, DCCs in the neoadjuvant setting will be studied.
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Physical activity in Fontan patients has a positive effect on cardiopulmonary capacity. Peak oxygen uptake represents the most robust predictor for morbidity and mortality in these children. It can be improved through exercise. High-intensity interval training (HIIT) represents the most efficient method, but the implementation is difficult. An App-based training represents an alternative with the possibility of providing positive feedback through a Fitness tracker.
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In breast cancer, the success of neoadjuvant chemotherapy depends on tumor-infiltrating lymphocytes and their specificity, especially against neoantigens - promising targets for immunotherapies. 3D-cell cultures offer a more realistic representation of tumor-immune cell interactions than conventional ones. The project seeks to compare 4 T-cell receptor-based immunotherapies against neoantigens in 2D- and 3D-models, aiming to identify the most promising approach for potential future treatments.
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As a result of non-specific inhibition, tyrosine kinase inhibitors (TKIs) also affect bone and cartilage development. Children and adolescents therefore suffer from significant growth retardation during therapy. Alternative therapy concepts are therefore urgently needed. In the proposed project, the influences of different TKIs on bone metabolism and cartilage differentiation will be investigated.
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Indirect capping of the dental pulp is recommended in deep cavities, but there is little clinical evidence for the success of the procedure. In an innovative simulation model of the pulp-dentin-complex, the effect of different biocompatible capping materials on human pulp cells through a dentin barrier will be tested. By analyzing cell survival, gene expression, oxidative stress and cytokine production, their bioactive effects will be compared in a way that is not possible in vivo.
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Our overarching goal is to enable robust metabolic & multi-parametric brain MRI at 7T in a clinical context. Therefore, a fast and precise motion correction is important, which we aim to realize in this ELAN-project by a deep learning-based registration. From the specific 7T contrasts of interest such as CEST and QSM, at first a virtual reference MPRage will be synthesized, which is registered in the following.
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Chronic stress has long-lasting effects on the hippocampal function, but it still remains unclear how. We investigate stress-induced epigenetic changes as a biological link between chronic stress and brain dysfunction. Our preliminary data has identified lamin B1 as a target of chronic stress. Lamin B1 is an epigenetic factor that maintains heterochromatin. We will investigate how chronic stress downregulates lamin B1, and how stress-induced reduction of lamin B1 affects epigenetic regulation.
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Our preliminary results suggest that AnnexinA1, which is expressed by dying cells within the bone marrow niche, will bind to Dectin-1 on osteoclasts to induce osteoclast differentiation and bone resorption in non-inflammatory conditions. Therefore, I will analyse the molecular mechanism of AnnexinA1 induced Dectin-1 signaling. Furthermore, I aim to define the AnnexinA1 expressing myeloid cell population within the bone marrow niche and its impact on osteoclast differentiation.
The aim of this project is to better understand the influence of T cells and the NLRP3 inflammasome in the context of multiple system atrophy (MSA). Therefore, an already established transgenic mouse model and human brain tissue from MSA patients will be used. The aim is to lay the groundwork for further projects using T cells and NLRP3 as potential pharmacological targets for MSA treatment.
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Skin autoimmunity consist in an aberrant immune response involving complex interactions between immune and stromal cells. Systemic sclerosis (SSc) is a skin autoimmune disorder with primary fibrotic components. Distinct fibroblasts subsets relevant in SSc have been identified, but to date is not known their spatial relationships with immune cells. Their role in SLE is also unknown. We plan to use a spatial multi-omics approach to better understand these processes.
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We present a project that aims to characterize the pediatric enteric nervous system (ENS) based on analyses of pediatric intestinal tissue, blood and stool. The interaction between the microbiome and the ENS in children will be focused as well as its influence on immunological responses. The complex processes of the pediatric microbiome-gut-brain axis have not yet been investigated and might be crucial in the pathogenesis of other diseases.
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HCMV glycoprotein B variants are being studied with respect to viral fusion and syncytium formation. The specific objectives are: (1) identification of polymorphisms that enhance or inhibit fusion; (2) characterization of the fusion phenotype of these viruses in different cell lines; and (3) development of a murine CMV with hyperfusogenic gB. This study aims to understand the regulation of gB fusion activity and to identify potential diagnostic markers for HCMV pathogenicity.
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Kidney transplanted patients are at a high risk for infections including sepsis. In the event of sepsis, a balance must be found between potentially life-saving immune defense and trans-plant protective immunosuppression. Fort he targeted treatment of sepsis in transplant pati-ents, we intend to identify immunological and in particular lymphocytic markers that might allow a more patientoriented, individualized therapeutic management in the future.
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The application aims to investigate endometrial cancers with regard to new molecular classifications. The ENCORE project studies real-world survival based on molecular patterns, analyzes the immune environment of tumors with concurrent p53 mutations, and correlates the eosinophil to lymphocyte ratio with patient outcome. In addition, the relevance of hormone and HER2 receptors in the individual molecular subtypes is examined.
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The project aims to explore differences in how neonatal and adult intestinal epithelial cells respond to microbial metabolites. As the first line of immune defense, epithelial cells regulate the balance between tolerance and immune responses. The impact of bacterial colonization on gut maturation is poorly understood but may shape future immune responses. This study will shed light on how early-life events influence immune development and their role in autoimmune diseases like IBD, MS, and SLE.
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Chondrosarcomas are malignant bone tumors, which do not respond to existing chemo- and radiotherapy. Preliminary studies could show that the the natural compound Garcinol strongly reduces proliferation and colony formation of these tumor cells. Additionally, Garcinol could re-sensitize chondrosarcoma cells to the chemotherapeutic Cisplatin. We therefore want to investigate the role of Garcinol as a new therapeutic option for chondrosarcoma.
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The aim of this project is to generate differentiated, axially vascularized and neurotized skeletal muscle tissue from ADSC and myoblasts on PCL-collagen I-(PANi)-nanofiber scaffolds. For this, seeded nanofiber scaffolds of PCL-collagen I with and without Polyanilin (4%) will be implanted in the neurotized vascular loop model of the rat for 6 weeks. Afterwards the myogenic differentiation will be analysed with the hypothesis, that the addition of PANi (4%) improves myogenic differentiation.
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In this project, the role of the AP-1 transcription factor Fos-like 2 (FOSL2) in tumor dormancy of malignant melanoma is investigated. Based on a 3D biofabricated dormancy model, preliminary work has shown that FOSL2 is highly expressed in dormant melanoma cells and that its downregulation prevents the formation of dormancy in these cells. The influence of extracellular factors on FOSL2 and potential target genes are being investigated in the 3D printed system.
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Obesity is marked by excessive lipid accumulation, leading to chronic inflammation in adipose tissue (AT), due to an increase in inflammatory immune cells causing insulin resistance and fat accumulation in other organs like the liver. This project focuses on the role of the immunomodulatory CD83 molecule in in lipid metabolism and obesity-related immune regulation in AT and the liver, potentially providing insights for new therapeutic strategies against obesity.
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The aim of this project is to establish a kidney organoid model to study complement activation in acute kidney injury. The model will first be optimized in terms of complexity and structure. Once established the kidney organoids will be used for co-culture experiments with immune cells, a hypoxia model of acute kidney injury and studies of the complement system. The development of the renal organoid model will contribute to the understanding of signalling pathways and therapeutic strategies.
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With this bridging grant, we are requesting support for our ongoing work on the role of the Hippo signaling pathway regulators YAP1, TAZ, TEAD1 und TEAD4 in skeletal muscle, especially in early myogenesis, skeletal muscle development and in adult skeletal muscle fibers. The results of this work will help us to revise and submit our DFG proposal and manuscript (for Nucleic Acids Research) and to continue funding the PhD theses involved.
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We are investigating the phenotypic diversity of patient-specific PAX2 variants in kidney diseases such as CAKUT and SRNS. For this purpose, we differentiate patient-derived iPSCs into various kidney cells in 2D and 3D organoids, compared with healthy control cells and gene-corrected variants. This approach helps to understand genetic and environmental factors in kidney diseases and to develop personalized therapies
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Extracellular vesicles (EVs) are membrane-bound nanoparticles essential for cell communication and organogenesis. We hypothesize that human breast milk-derived EVs (HBM-EVs) enhance intestinal maturation and regeneration. This study investigates HBM-EV protection in DSS-induced intestinal injury in zebrafish larvae, analyzing cell-morphology, inflammation, and tissue repair (Phalloidin, cleaved Caspase-3, TNF-?, Wnt5a), comparing EVs from three lactation stages.
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Borna Disease Virus 1 (BoDV-1) causes fatal encephalitis in humans. This project aims to generate recombinant variants of the glycoprotein G via structure-guided vaccine design. The G variants will be conjugated to the surface of liposomes that incorporate biomolecular adjuvants to boost immunogenicity. Optionally, we aim to mimic a live-attenuated vaccine by additional encapsulation of viral structural proteins. The BoDV-1 liposomes would be used in future studies with antibody-humanized mice.
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PAINMAP-IBD explores whether cutaneous sensory afferents can serve as a surrogate marker of visceral nerve dysfunction in IBD-associated abdominal pain. Using abdominal quantitative sensory testing (QST) and C-fiber-selective stimulation, the project characterizes sensory phenotypes and peripheral neurofunction. Findings will be correlated with clinical activity, biomarkers, and treatment response across defined patient cohorts.