A5034445397- Glioma Diagnosis and Treatment
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Lymphoma Diagnosis and Treatment
- CNS Lymphoma Diagnosis and Treatment
- Neurogenesis and neuroplasticity mechanisms
- Cancer Cells and Metastasis
- CAR-T cell therapy research
- Mathematical Biology Tumor Growth
- Chronic Lymphocytic Leukemia Research
- Brain Metastases and Treatment
- Studies on Chitinases and Chitosanases
- bioluminescence and chemiluminescence research
- Viral-associated cancers and disorders
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- Immunotherapy and Immune Responses
- Bioinformatics and Genomic Networks
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Click Chemistry and Applications
- Gene Regulatory Network Analysis
- Biotin and Related Studies
- Chemical Reactions and Isotopes
- Ocular Oncology and Treatments
German Cancer Research Center
2020-2025
Heidelberg University
2020-2025
National Center for Tumor Diseases
2020-2025
University Hospital Heidelberg
2020-2025
Heidelberg University
2024
Deutschen Konsortium für Translationale Krebsforschung
2024
DKFZ-ZMBH Alliance
2023
Abstract Both the perivascular niche (PVN) and integration into multicellular networks by tumor microtubes (TMs) have been associated with progression resistance to therapies in glioblastoma, but their specific contribution remained unknown. By long-term tracking of cell fate dynamics live mouse brain, differential therapeutic responses both niches are determined. PVN, a preferential location quiescent glioma cells, network facilitate against cytotoxic effects radiotherapy...
Recordings of the physiological history cells provide insights into biological processes, yet obtaining such recordings is a challenge. To address this, we introduce method to record transient cellular events for later analysis. We designed proteins that become labeled in presence both specific activity and fluorescent substrate. The recording period set by substrate, whereas controls degree labeling. use distinguishable substrates enabled successive periods activity. recorded...
Abstract Background Glioblastomas are characterized by aggressive and infiltrative growth, striking heterogeneity. The aim of this study was to investigate whether tumor cell proliferation invasion interrelated, or rather distinct features different populations. Methods Tumor were longitudinally determined in real-time using 3D vivo 2-photon laser scanning microscopy over weeks. Glioblastoma cells expressed fluorescent markers that permitted the identification their mitotic history cycling...
Abstract Background Glioblastoma is the most frequent and a particularly malignant primary brain tumor with no efficacy-proven standard therapy for recurrence. It has recently been discovered that excitatory synapses of AMPA-receptor subtype form between non-malignant neurons cells. This neuron-tumor network connectivity contributed to glioma progression could be efficiently targeted EMA/FDA approved antiepileptic AMPA receptor inhibitor perampanel in preclinical studies. The PerSurge trial...
Abstract Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. However, the determination of TM-interconnectivity in individual tumors is challenging impact on patient survival unresolved. Here, we establish connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) using dye uptake methodology, validate it recording cellular calcium epochs clinical correlations....
Primary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained via surgery or biopsy, cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses.
Brain metastases (BM) are a frequent complication of malignant melanoma (MM), with limited treatment options and poor survival. Prevention BM could be more effective better tolerated than treating established in various conditions.
Abstract Immunodeficiency-associated primary CNS lymphoma (PCNSL) represents a distinct clinicopathological entity, which is typically Epstein-Barr virus-positive (EBV + ) and carries an inferior prognosis. Genetic alterations that characterize EBV-related lymphomagenesis remain unclear precluding molecular classification targeted therapies. In this study, comprehensive genetic analysis of 22 EBV PCNSL, therefore, integrated clinical pathological information with exome RNA sequencing...
Malignant gliomas including glioblastomas are characterized by a striking cellular heterogeneity, which includes subpopulation of glioma cells that becomes highly resistant integration into tumor microtube (TM)-connected multicellular networks. A novel functional approach to detect, isolate, and characterize cell subpopulations with respect in vivo network is established, combining dye staining method intravital two-photon microscopy, Fluorescence-Activated Cell Sorting (FACS), molecular...
Abstract Recent technological advances in molecular diagnostics through liquid biopsies hold the promise to repetitively monitor tumor evolution and treatment response of brain malignancies without need invasive surgical tissue accrual. Here, we implemented a mass spectrometry‐based protein analysis pipeline which identified hundreds proteins 251 cerebrospinal fluid (CSF) samples from patients with four types (glioblastoma, lymphoma, metastasis, leptomeningeal disease [LMD]) healthy...
Tumor cell networks formed by tumor microtubes (TMs) may play a key role in the development of therapy resistance glioblastoma (GB). TM-mediated detoxification from radiation-induced reactive oxygen species (ROS) infer radioresistance. We hypothesize that high linear energy transfer (LET) radiation, which describes amount deposited radiation per unit length, interacts directly with DNA backbone to induce complex lesions and thus might be less dependent on mechanisms. Therefore, we sought...
Abstract Background 5q-associated spinal muscular atrophy (SMA) is a monogenic disease causing progressive alpha motor neuron degeneration, muscle atrophy, and weakness. Intrathecal therapy with the antisense oligonucleotide nusinersen modifies course. However, biomarkers for understanding underlying molecular pathomechanisms monitoring are not yet known. Methods A total of 130 cerebrospinal fluid (CSF) samples from 24 adult patients SMA type 2 or 3 were collected over 3.5 years, CSF...
Glioblastoma (GBM) progression and therapeutic resistance are significantly influenced by complex interactions between tumor cells the brain microenvironment, particularly neurons. However, studying these in physiologically relevant conditions has remained challenging due to limitations existing model systems. Here, we present hGliCS (human glioma-cortical spheroid), a novel fully human that overcomes key of current approaches combining patient-derived GBM with mature cortical neurons...
Targeted immunotherapies are of growing interest in the treatment various cancers. B7 homolog 3 protein (B7-H3), a member co-stimulatory/-inhibitory B7-family, exerts immunosuppressive and pro-tumorigenic functions cancer types is under evaluation ongoing clinical trials. Unfortunately, interaction partner(s) remain unknown which restricts druggability.Aiming to identify potential binding B7-H3, yeast two-hybrid mass spectrometry screen were performed. Potential candidates evaluated by...
Neuroligin 4 X-linked (NLGN4X) harbors a human leukocyte antigen (HLA)-A*02-restricted tumor-associated antigen, overexpressed in gliomas, that was found to induce specific cytotoxic T cell responses following multi-peptide vaccination patients with newly diagnosed glioblastoma. receptor (TCR) discovery performed using droplet-based single-cell TCR sequencing of NLGN4X-tetramer-sorted cells postvaccination. The identified delivered Jurkat and primary (NLGN4X-TCR-T). Functional profiling...
Abstract Background Gliomas evade current therapies through primary and acquired resistance the effect of temozolomide is mainly restricted to methylguanin‐O6-methyltransferase promoter (MGMT) hypermethylated tumors. Further markers are largely unknown would help for better stratification. Methods Clinical data methylation profiles from NOA‐08 (104, elderly glioblastoma) EORTC 26101 (297, studies 398 patients with glioblastoma Heidelberg Neuro‐Oncology center have been analyzed focused on...
Abstract Purpose This study investigates the biological effect of Tumor Treating Fields (TTFields) on key drivers glioblastoma’s malignancy—tumor microtube (TM) formation—and function and overall integrity tumor cell network. Method Using a two-dimensional monoculture GB network model (2DTM) primary glioblastoma (GBC) cultures (S24, BG5 or T269), we evaluated effects TTFields density, interconnectivity structural We also analyzed calcium (Ca 2+ ) transient dynamics morphology, validating...
PurposeInfiltrative growth pattern is a hallmark of glioblastoma (GBM). Radiation therapy aims to eradicate microscopic residual GBM cells after surgical removal the visible tumor bulk. However, in-field recurrences remain major failure. We hypothesized that radiosensitivity peripheral invasive (peri) may differ from predominantly investigated bulk.Methods and MaterialsInvasive populations were generated via debulking core serial orthotopic transplantation peri cells, sustained proinvasive...
Abstract Background Epstein-Barr virus (EBV)+ and EBV- primary CNS lymphomas (PCNSL) carry distinct mutational landscapes, but their transcriptional epigenetic profiles have not been integrated compared. This precludes further insights into pathobiology molecular differences, relevant for classification targeted therapy. Methods Twenty-three 15 EBV+ PCNSL, histologically classified as diffuse large B-cell lymphomas, were subjected to RNA-sequencing EPIC methylation arrays. Unsupervised...
Abstract Tumor cell extensions called tumor microtubes (TMs) in glioma resemble neurites during neurodevelopment and connect cells to a network that has considerable relevance for progression therapy resistance. The determination of interconnectivity individual tumors been challenging the impact connectivity on patient survival remained unresolved so far. Here, signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) was established clinically validated....
Abstract Despite the remarkable success of chimeric antigen receptor (CAR)-T cell treatment for patients with hematologic malignancies, this method has yet failed to confer meaningful survival benefits suffering from glioblastoma (GB), most lethal type brain tumor. This highlights need develop novel CAR-T approaches disease. CD70 is a member tumor necrosis factor (TNFR) superfamily. Although absent on normal tissue, it ectopically expressed in substantial fraction GB patients, indicating its...
Abstract Protein kinases control most cellular processes and aberrant kinase activity is involved in numerous diseases. To investigate the link between specific activities phenotypes heterogeneous cell populations vivo , we introduce molecular recorders of for later analysis. Based on split-HaloTag a phosphorylation-dependent switch, our become rapidly labeled presence fluorescent HaloTag substrate. The given controls degree labeling whereas recording window set by We have designed four...