A5045366159- Pluripotent Stem Cells Research
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- 3D Printing in Biomedical Research
- Genomics and Chromatin Dynamics
- Multiple Myeloma Research and Treatments
- Genomics and Phylogenetic Studies
- Platelet Disorders and Treatments
- Cellular transport and secretion
- Renal Diseases and Glomerulopathies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Neurogenetic and Muscular Disorders Research
- CRISPR and Genetic Engineering
- Advanced Fluorescence Microscopy Techniques
- Bariatric Surgery and Outcomes
- Protein Degradation and Inhibitors
- Cell Image Analysis Techniques
- Algebraic Geometry and Number Theory
- Computational Drug Discovery Methods
- Nerve injury and regeneration
- CAR-T cell therapy research
- Cloud Data Security Solutions
- Cellular Mechanics and Interactions
University of Würzburg
2020-2024
Universitätsklinikum Würzburg
2021
Roche (Switzerland)
2011-2019
University of Bamberg
2018
Heidenhain (Germany)
2018
TU Dresden
2009-2014
Australian National University
2003
Max Planck Institute of Biochemistry
2002
Abstract Small molecule splicing modifiers have been previously described that target the general machinery and thus low specificity for individual genes. Several potent molecules correcting deficit of SMN2 (survival motor neuron 2) gene identified these are moving towards a potential therapy spinal muscular atrophy (SMA). Here by using combination RNA splicing, transcription, protein chemistry techniques, we show directly bind to two distinct sites pre-mRNA, thereby stabilizing yet...
The long-tailed macaque, also referred to as cynomolgus monkey ( Macaca fascicularis ), is one of the most important nonhuman primate animal models in basic and applied biomedical research. To improve predictive power experiments for humans, we determined genome sequence a female Mauritian origin using whole-genome shotgun sequencing approach. We template switch strategy that uses either rhesus or human assemble reads. sixfold coverage draft enabled discovery about 2.1 million potential...
Function as a Service (FaaS) is young and rapidly evolving cloud paradigm. Due to its hardware abstraction, inherent virtualization problems come into play need an assessment from the FaaS point of view. Especially avoidance idling scaling on demand cause lot container starts consequence cold for users. The aim this paper address start problem in benchmark investigate influential factors duration perceived start. We conducted AWS Lambda Microsoft Azure Functions with 49500 function...
Abstract Identification of novel antibiotics remains a major challenge for drug discovery. The present study explores use phenotypic readouts beyond classical antibacterial growth inhibition adopting combined multiparametric high content screening and genomic approach. Deployment the semi-automated bacterial fingerprint (BPF) profiling platform in conjunction with machine learning-powered dataset analysis, effectively allowed us to narrow down, compare predict compound mode action (MoA)....
Antigen-specific neuroinflammation and neurodegeneration are characteristic for neuroimmunological diseases. In Parkinson's disease (PD) pathogenesis, α-synuclein is a known culprit. Evidence α-synuclein-specific T cell responses was recently obtained in PD. Still, causative link between these dopaminergic had been lacking. We thus addressed the functional relevance of immune PD mouse model. utilized model which an Adeno-associated Vector 1/2 serotype (AAV1/2) expressing human mutated...
Direct transdifferentiation of somatic cells is a promising approach to obtain patient-specific for numerous applications. However, conversion across germ-layer borders often requires ectopic gene expression with unpredictable side effects. Here, we present gene-free that allows efficient human fibroblasts via transient progenitor stage into Schwann cells, the major glial cell type peripheral nerves. Using multikinase inhibitor, transdifferentiated neural precursors were subsequently further...
A major challenge for RNA-seq analysis of gene expression is to achieve sufficient coverage informative nonribosomal transcripts. In eukaryotic samples, this typically achieved by selective oligo(dT)-priming messenger RNAs exclude ribosomal RNA (rRNA) during cDNA synthesis. However, strategy not compatible with prokaryotes in which functional transcripts are generally polyadenylated. To overcome this, we adopted DASH ( d epletion a bundant s equences h ybridization), initially developed...
The initial step of bone digestion is the adhesion osteoclasts onto surfaces and assembly podosomal belts that segregate bone-facing ruffled membrane from other domains. During digestion, components border also need to be recycled after macropinocytosis digested materials. How osteoclast polarity recycling are coordinated remains unknown. Here, we show Cdc42-guanine nucleotide exchange factor FGD6 coordinates these events through its Src-dependent interaction with different actin-based...
Bone digestion occurs when osteoclasts adhere onto bone surfaces and polarize to form acidic, hydrolase-rich resorption lacunae. For this process, they condense their actin-rich podosomes in tight belts establish sealing zones, which segregate basal membranes from those facing This polarization process remains poorly understood. Here, we combined quantitative proteomics gene silencing identify new substrates of the Src tyrosine kinase, a key regulator osteoclast function. We now report that...
The cardiovascular and immune systems undergo profound intertwined alterations with aging. Recent studies have reported that an accumulation of memory terminally differentiated T cells in elderly subjects can fuel myocardial aging boost the progression heart diseases. Nevertheless, it remains unclear whether immunological senescence profile is sufficient to cause age-related cardiac deterioration or merely acts as amplifier previous tissue-intrinsic damage. Herein, we sought decompose...
CEA TCB is a novel T-cell-bispecific (TCB) antibody targeting the carcinoembryonic antigen (CEA) expressed on tumor cells and CD3 epsilon chain (CD3e) present T cells, which currently in Phase 1 clinical trials (NCT02324257) for treatment of CEA-positive solid tumors. Because human (hCEA) binder does not cross-react with cynomolgus monkey absent rodents, alternative nonclinical safety evaluation approaches were considered. These included development cross-reactive homologous (surrogate)...
GFP has established itself as a highly useful tool throughout many areas of modern biology. Recently, the novel fluorescent protein drFP583, also termed DsRed or RFP, was clonedfrom coral Discosoma genus. The is only weakly homologous to and red emission spectrum, which makes drFP583 an attractive candidate for in vivo double labeling together with variants. However, wildtype several drawbacks, including inefficient folding protein, extremely slow maturation chromophore, tetramerization even...
In the past decade Göttingen minipig has gained increasing recognition as animal model in pharmaceutical and safety research because it recapitulates many aspects of human physiology metabolism. Genome-based comparison drug targets together with quantitative tissue expression analysis allows rational prediction pharmacology cross-reactivity drugs models thereby improving attrition which is an important challenge process development. Here we present a new chromosome level based version genome...
G6b-B is a megakaryocyte lineage-specific immunoreceptor tyrosine-based inhibition motif-containing receptor, essential for platelet homeostasis. Mice with genomic deletion of the entire Mpig6b locus develop severe macrothrombocytopenia and myelofibrosis, which reflected in humans null mutations MPIG6B. The current model proposes that megakaryocytes lacking normally, whereas proplatelet release hampered, but underlying molecular mechanism remains unclear. We report on spontaneous recessive...
Vascular leakage is a serious side effect of therapies based on monoclonal antibodies or cytokines which may lead to life-threatening situations. With the steady increase new drug development programs for large molecules, there an urgent need reliable tools assess this potential liability medicines in rapid and cost-effective manner. Using human umbilical vein endothelial cells (HUVECs) as model endothelium, we established impedance-based assay measuring integrity cell monolayer real time....
Abstract Damage to thinly myelinated and unmyelinated nerve fibers causes small fiber pathology, which is increasingly found in pain syndromes such as neuropathy (SFN) fibromyalgia syndrome (FMS). The peripheral endings of the terminate within epidermis, where they are surrounded by keratinocytes that may act primary nociceptive transducers. We performed RNA sequencing obtained from patients with SFN, FMS, healthy controls. 141 deregulated protein coding genes between SFN controls no...
Treatment options for NAFLD are still limited. Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB), has been shown to improve metabolic and histologic markers of NAFLD. Glucagon-like-peptide-1 (GLP-1) analogues lead improvements in phase 2 clinical trials. We directly compared the effects RYGB with a treatment using liraglutide and/or peptide tyrosine 3-36 (PYY3-36) rat model early Obese male Wistar rats (high-fat diet (HFD)-induced) were randomized into following groups: RYGB,...
Abstract Multiple myeloma (MM) is a genetically heterogeneous disease and the management of relapses one biggest clinical challenges. TP53 alterations are established high‐risk markers included in current staging criteria. KRAS most frequently mutated gene affecting around 20% MM patients. Applying Clonal Competition Assays (CCA) by co‐culturing color‐labeled modified cell models, we recently showed that mono‐ biallelic transmit fitness advantage to cells. Here, report similar dynamic for...
Abstract Due to their broad differentiation potential, pluripotent stem cells (PSCs) offer a promising approach for generating relevant cellular models various applications. While human PSC-based are already advanced, similar systems non-human primates (NHPs) still lacking. However, as NHPs the most appropriate animals evaluating safety of many novel pharmaceuticals, availability in vitro would be extremely useful bridge gap between and animal models. Here, we present NHP endothelial cell...
Copy number variations (CNVs) are a significant source of genetic diversity and commonly found in mammalian genomes. We have generated genome-wide CNV map for Cynomolgus monkeys (Macaca fascicularis). This crab-eating macaque is the closest animal model to humans that used biomedical research.We show monkey CNVs general much smaller size than gene loci specific population origin. Genome-wide expression data from five vitally important organs demonstrates close proximity transcription start...