A5010522132- Blood disorders and treatments
- Neutropenia and Cancer Infections
- Acute Myeloid Leukemia Research
- CRISPR and Genetic Engineering
- Immunodeficiency and Autoimmune Disorders
- Erythrocyte Function and Pathophysiology
- Pluripotent Stem Cells Research
- Sirtuins and Resveratrol in Medicine
- Renal and related cancers
- Caveolin-1 and cellular processes
- PARP inhibition in cancer therapy
- RNA Interference and Gene Delivery
- Cytomegalovirus and herpesvirus research
- Metabolism and Genetic Disorders
- Biomedical Ethics and Regulation
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Water Treatment and Disinfection
- Genetic factors in colorectal cancer
- Calcium signaling and nucleotide metabolism
- DNA Repair Mechanisms
- Platelet Disorders and Treatments
- Autophagy in Disease and Therapy
- Viral Infectious Diseases and Gene Expression in Insects
- Biosensors and Analytical Detection
- Microbial Community Ecology and Physiology
University of Tübingen
2015-2024
University Children's Hospital Tübingen
2019-2024
Pluripotent stem cells must strictly maintain genomic integrity to prevent transmission of mutations. In human induced pluripotent (iPSCs), we found that genome surveillance is achieved via two ways, namely, a hypersensitivity apoptosis and very low accumulation DNA lesions. The threshold was mediated by constitutive p53 expression marked upregulation proapoptotic target genes the BCL-2 family, ensuring efficient iPSC removal upon genotoxic insults. Intriguingly, despite elevated...
A Autosomal-dominant ELANE mutations are the most common cause of severe congenital neutropenia. Although majority neutropenia patients respond to daily granulocyte colony stimulating factor, approximately 15 % do not this cytokine at doses up 50 μg/kg/day and will develop myelodysplasia or acute myeloid leukemia. “Maturation arrest,” failure marrow progenitors form mature neutrophils, is a consistent feature associated As mutant neutrophil elastase abnormality, we hypothesized that could be...
Beyond classical roles in thrombosis and haemostasis, it becomes increasingly clear that platelets contribute as key players to inflammatory processes. The involvement of these processes is often mediated through a variety platelet-derived chemokines which are released upon activation act paracrine autocrine factors. In this study, we investigate CXCL14, newly described platelet chemokine its role thrombus formation well monocyte migration. addition, examine the receptor CXCR4 possible for...
CRISPR/Cas9-mediated gene editing of stem cells and primary cell types has several limitations for clinical applications. The direct delivery ribonucleoprotein (RNP) complexes consisting Cas9 nuclease guide RNA (gRNA) improved DNA- virus-free modifications, but it does not enable the essential enrichment gene-edited cells. Here, we established a protocol fluorescent labeling CRISPR/Cas9-gRNA RNP in human hematopoietic progenitor (HSPCs) induced pluripotent (iPSCs). As proof principle genes...
The four OSKM factors OCT4, SOX2, KLF4 and c-MYC are key transcription modulating pluripotency, self-renewal tumorigenesis in stem cells. However, although their transcriptional targets have been extensively studied, little is known about how these regulated at the posttranslational level. In this study, we established an vitro system to identify phosphorylation patterns of by AKT kinase. were expressed Sf9 insect cells employing baculoviral expression system. SOX2 localized nucleus cells,...
Nicotinamide phosphoribosyltransferase (NAMPT) regulates cellular functions through the protein deacetylation activity of nicotinamide adenine dinucleotide (NAD+)-dependent sirtuins (SIRTs). SIRTs regulate histones and none-histone proteins. The role NAMPT/SIRT pathway in regulation maintenance differentiation human-induced pluripotent stem (iPS) cells is not fully elucidated. We evaluated effects specific inhibitors NAMPT or SIRT2 on pluripotency, proliferation, survival, hematopoietic...
DNA damage and changes in the mitochondrial content have been implicated ageing cancer development. To prevent genomic instability tumorigenesis, cells must maintain integrity of their nuclear DNA. Advances research protection stability, however, also depend on availability techniques that can reliably quantify alterations copy numbers lesions an accurate high-throughput manner. Unfortunately, no such method has established yet. Here, we describe high-sensitivity long-run real-time PCR...
Safety considerations for gene therapies of inherited preleukemia syndromes, including severe congenital neutropenia (CN), are paramount. We compared several strategies CRISPR/Cas9 editing autosomal-dominant
Pluripotent stem cells must be endowed with efficient genome surveillance. Here we describe the multiple mechanisms that ensure their integrity, including high susceptibility to apoptosis and prevention of DNA lesions. In induced pluripotent cells, hypersensitivity is mediated by increased expression proapoptotic BCL-2 protein, whereas damage prevented upregulation several antioxidant enzymes. Antioxidants might therefore employed for safer cell therapies.
Abstract Transmembrane L1 cell adhesion molecule (L1CAM) is widely used as a marker to enrich for neuron-derived extracellular vesicles (EVs), especially in plasma. However, this approach lacks sufficient robust validation. This study aimed assess whether human biofluids are indeed enriched EVs, particularly by L1CAM immunoaffinity, utilizing multiple sources (plasma, CSF, conditioned media from iPSC-derived neurons [iNCM]) and different methods (mass spectrometry [MS], nanoparticle tracking...
Mutations in the ELANE gene, encoding neutrophil elastase (NE) protein, are responsible for most CyN cases and approximately 25 % of CN cases. In CyN, a median 2.8 CD34+ cells were early CD49f+ hematopoietic stem (eHSC) that did not express thus escape from unfolded protein response (UPR) caused by mutated NE. respond to G-CSF with significant upregulation stem-cell-specific transcription factors, C/EBP/, MLL1, HOXA9, MEIS1, HLF during ascending arm cycle, resulting differentiation myeloid...
Severe congenital neutropenia (CN) is a pre-leukemic bone marrow failure syndrome that can progress to acute myeloid leukemia (CN/AML). Patient material study leukemogenesis, especially hematopoietic progenitor cells (HPCs) limited and hard access. We have established protocol for generation of HPCs from iPSCs followed by HPC expansion on Sl/Sl feeder expressing FLT3L. performed drug treatment iPSC-derived or under feeder-free conditions. Our also suitable primary blasts. For complete...