A5011815129- Pancreatic function and diabetes
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Renal and related cancers
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Energy Harvesting in Wireless Networks
- Tissue Engineering and Regenerative Medicine
- PARP inhibition in cancer therapy
- Neonatal Respiratory Health Research
- 3D Printing in Biomedical Research
- Congenital heart defects research
- Cancer Cells and Metastasis
- Law, AI, and Intellectual Property
- DNA Repair Mechanisms
- Tumors and Oncological Cases
- Microtubule and mitosis dynamics
- Pancreatitis Pathology and Treatment
- Liver Disease Diagnosis and Treatment
- Bladder and Urothelial Cancer Treatments
- Radiation Therapy and Dosimetry
- Cystic Fibrosis Research Advances
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- Single-cell and spatial transcriptomics
University Hospital Ulm
2014-2024
Universität Ulm
2015-2022
Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie
2021
Objective The generation of acinar and ductal cells from human pluripotent stem (PSCs) is a poorly studied process, although various diseases arise this compartment. Design We designed straightforward approach to direct PSCs towards pancreatic organoids resembling progeny. Results Extensive phenotyping the not only shows appropriate marker profile but also ultrastructural, global gene expression functional hallmarks pancreas in dish. Upon orthotopic transplantation into immunodeficient mice,...
Pancreatic ductal adenocarcinomas (PDAC) harbor recurrent functional mutations of the master DNA damage response kinase ATM, which has been shown to accelerate tumorigenesis and epithelial-mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated molecular effects conditional Atm deletion a mouse model PDAC. was associated with increased mitotic defects, genomic rearrangements, deregulated checkpoints, reminiscent human We hypothesized that...
Pluripotency represents a cell state comprising fine-tuned pattern of transcription factor activity required for embryonic stem (ESC) self-renewal. TBX3 is the earliest expressed member T-box family and involved in maintenance induction pluripotency. Hence, believed to be key pluripotency circuitry, with loss coinciding We report dynamic expression vitro vivo using genetic reporter tools tracking mouse ESCs (mESCs). Low levels are associated reduced pluripotency, resembling more mature...
Binary enterotoxins Clostridium (C.) botulinum C2 toxin, C. perfringens iota toxin and difficile CDT are composed of a transport (B) separate non-linked enzyme (A) component. Their B-components mediate endocytic uptake into mammalian cells subsequently the A-components from acidic endosomes cytosol, where latter ADP-ribosylate G-actin resulting in cell rounding death causing clinical symptoms. Protein folding enzymes, including Hsp90 peptidyl-prolyl cis/trans isomerases facilitate across...
Cell fate decisions and pluripotency, but also malignancy depend on networks of key transcriptional regulators. The T-box transcription factor TBX3 has been implicated in the regulation embryonic stem cell self-renewal cardiogenesis. We have recently discovered that forced expression cells promotes mesendoderm specification directly by activating lineage factors indirectly enhancing paracrine NODAL signalling. Interestingly, aberrant is associated with breast cancer melanoma formation. In...
Rationale: Pancreatic lineage specification follows the formation of tripotent pancreatic progenitors (PPs). Current protocols rebuilding PPs in vitro have an endocrine bias and are mostly based on PDX1/NKX6-1 coexpression neglecting other markers decisive for PP heterogeneity potential. However, true utmost interest to study also exocrine disorders such as cancer simultaneously generate all three lineages from same ancestor. Methods: Here, we performed a comprehensive compound testing...
Abstract Cell type specification during pancreatic development is tightly controlled by a transcriptional and epigenetic network. The precise role of most transcription factors, however, has been only described in mice. To convey such concepts to human development, alternative model systems as vitro differentiation pluripotent stem cells can be employed. Here, we analyzed stage-specific RNA-, ChIP-, ATAC-sequencing data dissect regulatory mechanisms development. Transcriptome open chromatin...
Patient-derived induced pluripotent stem cells (iPSCs) provide a unique platform to study hereditary disorders and predisposition syndromes by resembling germline mutations of affected individuals their potential differentiate into nearly every cell type the human body. We employed plucked hair from two siblings with family history cancer carrying pathogenic CDKN2A variant, P16-p.G101W/P14-p.R115L, generate patient-specific iPSCs in cancer-prone ancestry for downstream analytics. The...
The recapitulation of human developmental processes and pathological manifestations requires access to specific cell types precursor stages during embryogenesis disease. Here, we describe a scalable in vitro differentiation protocol guide pluripotent stem cells stepwise into pancreatic duct-like organoids. mimics duct development was successfully used model the onset progression ductal adenocarcinoma; approach is suitable for multiple downstream applications. However, cost- time-intensive....
Human pluripotent stem cells represent a powerful tool to study human embryonic development and disease but also open up novel strategies for cell replacement therapies. Their capacity give rise every type of the body, meanwhile, enables researchers generate high yields mesodermal, ectodermal, endodermal-derived tissues such as hepatic, pancreatic, or intestinal cells. Another progress in field came with advent 3-dimensional culture conditions, so-called organoids, which facilitate...
Despite intensive research and progress in personalized medicine, pancreatic ductal adenocarcinoma remains one of the deadliest cancer entities. Pancreatic duct-like organoids (PDLOs) derived from human pluripotent stem cells (PSCs) or patient-derived (PDOs) provide unique tools to study early late stage dysplasia foster medicine. However, such advanced systems are neither rapidly nor easily accessible require an vivo niche tumor formation interaction with stroma. Here, establishment porcine...
In a patient with permanent neonatal syndromic diabetes clinically similar to cases ONECUT1 biallelic mutations, we identified disease-causing deletion located upstream of ONECUT1. Through genetic, genomic and functional studies crucial regulatory region acting as an enhancer specifically during pancreatic development. This contains low-frequency variant showing strong association type 2 other glycemic traits, thus extending the contribution this common forms diabetes. Clinical relevance is...
Within the pancreas, Keratin 19 (KRT19) labels ductal lineage and is a determinant of pancreatic adenocarcinoma (PDAC). To investigate KRT19 expression dynamics, we developed human pluripotent stem cell (PSC)-based KRT19-mCherry reporter system in different genetic backgrounds to monitor from its endogenous gene locus. A differentiation protocol generate mature duct-like organoids was applied. While KRT19/mCherry became evident at early endoderm stage, mCherry signal present nearly all cells...
Abstract We have recently shown that loss of ORP3 leads to aneuploidy induction and promotes tumor formation. However, the specific mechanisms by which contributes ploidy-control cancer initiation progression is still unknown. Here, we report highly expressed in ureter bladder epithelium while its expression downregulated invasive cell lines during progression, both human mouse cancer. Moreover, observed an increase incidence N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced carcinoma...
Exocrine/ductal pancreatic differentiation from human pluripotent stem cells is a poorly understood process albeit various diseases arise this compartment. We designed straightforward approach to direct (PSC) toward organoids resembling exocrine and ductal progeny. Extensive phenotyping of the not only shows appropriate marker profile but also ultra-structural functional hallmarks pancreas in dish. Upon orthotopic transplantation into immunodeficient mice, these form normal ducts acinar...
Human pluripotent stem cells, with their ability to proliferate indefinitely and differentiate into virtually all cell types of the human body, provide a novel resource study development implement relevant disease models. Here, we employed pancreatic differentiation platform complemented an shRNA screen in cells (PSCs) identify potential drivers early endoderm development. Deep sequencing followed by abundancy ranking pinpointed six top hit genes potentially associated either improved or...
Abstract Background We have previously identified an unsuspected role for GJB3 showing that the deficiency of this connexin protein induces aneuploidy in human and murine cells accelerates cell transformation as well tumor formation xenograft models. The molecular mechanisms by which loss leads to cancer initiation progression remain unsolved. Methods expression levels were determined RT-qPCR Western blot. consequences knockdown on genome instability assessed metaphase chromosome counting,...