A5052566588- Neurobiology and Insect Physiology Research
- CAR-T cell therapy research
- Insect and Arachnid Ecology and Behavior
- Insect Utilization and Effects
- Virus-based gene therapy research
- Retinal Development and Disorders
- Medicinal Plants and Bioactive Compounds
- Photoreceptor and optogenetics research
- Viral Infectious Diseases and Gene Expression in Insects
- Neuroscience and Neuropharmacology Research
- Pharmacological Effects of Natural Compounds
- Olfactory and Sensory Function Studies
- Cytomegalovirus and herpesvirus research
- Neural dynamics and brain function
- Immune Cell Function and Interaction
- Silicon Carbide Semiconductor Technologies
- Biochemical effects in animals
- Plant biochemistry and biosynthesis
- Chronic Lymphocytic Leukemia Research
- Cholinesterase and Neurodegenerative Diseases
- Plant and Biological Electrophysiology Studies
- Acute Lymphoblastic Leukemia research
- Plant-based Medicinal Research
- Advancements in Semiconductor Devices and Circuit Design
- Biosimilars and Bioanalytical Methods
University Hospital Heidelberg
2017-2024
Heidelberg University
2016-2024
Leibniz Institute for Neurobiology
2013-2020
Leipzig University
2011
University of Würzburg
2003-2011
Abstract Background Third-generation chimeric antigen receptor (CAR)-engineered T cells (CARTs) might improve clinical outcome of patients with B cell malignancies. This is the first report on a third-generation CART dose-escalating, phase-1/2 investigator-initiated trial treating adult refractory and/or relapsed (r/r) acute lymphoblastic leukemia (ALL). Methods Thirteen were treated escalating doses CD19-directed CARTs between 1 × 10 6 and 50 CARTs/m 2 . Leukapheresis, manufacturing...
ABSTRACT Mapping brain function to structure is a fundamental task for neuroscience. For such an endeavour, the Drosophila larva simple enough be tractable, yet complex interesting. It features about 10,000 neurons and capable of various taxes, kineses Pavlovian conditioning. All its are currently being mapped into light-microscopical atlas, Gal4 strains generated experimentally access one at time. In addition, electron microscopic reconstruction nervous system seems within reach. Notably,...
An understanding of associative learning is facilitated if it can be analyzed in a simple animal like the fruit fly Drosophila. Here, we introduce first visual paradigm for larval Drosophila; this remarkable as larvae have an order magnitude fewer neurons than adult flies. Larvae were subjected to either two reciprocal training regimes: Light+/Dark- or Light-/Dark+. Subsequently, all individually tested their preference between Light versus Dark. The difference regimes was therefore...
Synapsins are evolutionarily conserved, highly abundant vesicular phosphoproteins in presynaptic terminals. They thought to regulate the recruitment of synaptic vesicles from reserve pool readily-releasable pool, particular when vesicle release is be maintained at high spiking rates. As regulation transmitter a prerequisite for plasticity, we use fruit fly Drosophila ask whether Synapsin has role behavioral plasticity as well; flies, encoded by single gene (syn). We tackled this question...
Synapsin is an evolutionarily conserved, presynaptic vesicular phosphoprotein. Here, we ask where and how synapsin functions in associative behavioral plasticity. Upon loss or reduction of a deletion mutant via RNAi, respectively, Drosophila larvae are impaired odor-sugar learning. Acute global expression local only the mushroom body, third-order "cortical" brain region, fully restores ability mutant. No rescue found by body input neurons excluding bodies. On molecular level, find that...
Chimeric antigen receptor (CAR) T cells are considered genetically modified organisms (GMOs) and constitute gene therapy medicinal products. Thus, CAR cell manufacturing for clinical application is strictly regulated. Appropriate methods to assess vector copy numbers (VCNs) in products monitoring of frequencies patients required. Quantitative polymerase chain reaction (qPCR) the preferred method VCN assessment. However, no standardized procedure with high reproducibility has been described...
Chimeric antigen receptor (CAR) T cells spark hope for patients with CD19+ B cell neoplasia, including relapsed or refractory (r/r) acute lymphoblastic leukaemia (ALL) r/r non-Hodgkin's lymphoma (NHL). Published studies have mostly used second-generation CARs 4-1BB CD28 as costimulatory domains. Preclinical results of third-generation incorporating both elements shown superiority concerning longevity and proliferation. The University Hospital Heidelberg is the first institution to run an...
In Drosophila , short-term (STH) and long-term habituation (LTH) of olfactory avoidance behavior are believed to arise from the selective potentiation GABAergic synapses between multiglomerular local circuit interneurons (LNs) projection neurons in antennal lobe. However, underlying mechanisms remain poorly understood. Here, we show that synapsin ( syn ) function is necessary for STH 97 -null mutant defects can be rescued by + cDNA expression solely LN1 subset interneurons. As a synaptic...
Adverse life events can induce two kinds of memory with opposite valence, dependent on timing: “negative” memories for stimuli preceding them and “positive” experienced at the moment “relief.” Such punishment relief are found in insects, rats, man. For example, fruit flies ( Drosophila melanogaster ) avoid an odor after odor-shock training (“forward conditioning” odor), whereas shock-odor (“backward odor) they approach it. Do these timing-dependent associative processes share molecular...
Larval Drosophila offer a study case for behavioral neurogenetics that is simple enough to be experimentally tractable, yet complex worth the effort. We provide detailed, hands-on manual Pavlovian odor-reward learning in these animals. Given versatility of genetic analyses, combined with evolutionarily shared heritage humans, paradigm has utility not only and experimental psychology, but translational biomedicine as well. Together upcoming total synaptic connectome nervous system...
Inspired from plant medicine, a drug that partially compensates for memory decline in aged flies and mice is identified.
: An experience with electric shock can support two opposing kinds of behavioral effects: Stimuli that precede during training are subsequently avoided as predictors for punishment, whereas stimuli follow later on approached, they predict relief. We show here, the fruit fly Drosophila, upon loss white-function, balance between these learning is distorted in favor punishment learning: white1118 mutants stronger and weaker relief learning, compared to wild type flies. Thus, establish, overall,...
Abstract Third-generation chimeric antigen receptor T cells (CARTs) for relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL) may improve efficacy compared to second-generation CARTs due their enhanced CAR design. We performed the first phase 1/2 investigator-initiated trial evaluating escalating doses of third-generation (HD-CAR-1) targeting CD19 in patients with r/r CLL and B-cell lymphoma. eligibility criteria were failure two therapy lines including at least one pathway...
The synapse-associated protein of 47 kDa (SAP47) is a member phylogenetically conserved gene family hitherto unknown function. In Drosophila , SAP47 encoded by single ( Sap47 ) and expressed throughout all synaptic regions the wild-type larval brain; specifically, electron microscopy reveals anti-SAP47 immunogold labeling within 30 nm presynaptic vesicles. To analyze function, we used viable fertile deletion mutant 156 which suffers from 1.7 kb in regulatory region first exon. cannot be...
Chimeric antigen receptor (CAR) T cell (CART) therapy has been established as a treatment option for patients with CD19-positive lymphoid malignancies in both the refractory and relapsed setting. Displaying significant responses clinical trials, two second-generation CART products directed against CD19, axicabtagene ciloleucel (axi-cel) tisagenlecleucel (tisa-cel), have approved integrated into routine. However, experimental assay quantitative monitoring of these treated open domain are...
Synapsin is an evolutionarily conserved presynaptic phosphoprotein. It encoded by only one gene in the Drosophila genome and expressed throughout nervous system. regulates balance between reserve releasable vesicles, required to maintain transmission upon heavy demand, essential for proper memory function at behavioral level. Task-relevant sensorimotor functions, however, remain intact absence of Synapsin. Using odor–sugar reward associative learning paradigm larval , we show that scores...
Rationale: Patients receiving an allogeneic stem cell graft from cytomegalovirus (CMV) seronegative donors are particularly prone to CMV reactivation with a high risk of disease and mortality.Therefore we developed manufactured novel vaccine initiated clinical phase I trial phosphoprotein 65 (CMVpp65)-derived peptide.Methods: Ten patients after transplantation received four vaccinations at biweekly interval.All were monitored for CMVpp65 antigenemia.Flow cytometry CMV-specific CD8 + γδ T...
Understanding social behaviour requires a study case that is simple enough to be tractable, yet complex remain interesting. Do larval Drosophila meet these requirements? In broad sense, this question can refer effects of the mere presence other larvae on target individual. Here we focused in more strict sense 'peer pressure', whether individual larva affected by what surrounding group doing. We found innate olfactory preference was neither (i) level nor (ii) expression learned group....
ABSTRACT Preparations of Rhodiola rosea root are widely used in traditional medicine. They can increase life span worms and flies, have various effects related to nervous system function different animal species humans. However, which the compounds R. is mediating any one these has remained unknown most cases. Here, an analysis volatile non-volatile low-molecular-weight constituents samples was accompanied by investigation their behavioral impact on Drosophila melanogaster larvae. attractive...