A5054981182- Venomous Animal Envenomation and Studies
- Healthcare and Venom Research
- Cancer Genomics and Diagnostics
- Neuroblastoma Research and Treatments
- Diptera species taxonomy and behavior
- Pancreatic and Hepatic Oncology Research
- Adrenal and Paraganglionic Tumors
- Coral and Marine Ecosystems Studies
- Cancer, Hypoxia, and Metabolism
- Genetic Neurodegenerative Diseases
- Endoplasmic Reticulum Stress and Disease
- Parasite Biology and Host Interactions
- Cancer Cells and Metastasis
- Yersinia bacterium, plague, ectoparasites research
- Autophagy in Disease and Therapy
- Cancer-related molecular mechanisms research
- Genetic factors in colorectal cancer
- Insect and Pesticide Research
- BRCA gene mutations in cancer
- PARP inhibition in cancer therapy
- Insect symbiosis and bacterial influences
- Genetic Syndromes and Imprinting
- RNA regulation and disease
- Neurogenetic and Muscular Disorders Research
- Marine Invertebrate Physiology and Ecology
Leipzig University
2017-2024
National Center for Tumor Diseases
2022-2024
Helmholtz-Zentrum Dresden-Rossendorf
2022-2024
University Hospital Carl Gustav Carus
2022-2024
German Cancer Research Center
2022-2024
Technische Universität Dresden
2022-2024
Heidelberg University
2022-2024
Deutschen Konsortium für Translationale Krebsforschung
2022-2024
German Cancer Society
2023-2024
University Hospital Heidelberg
2022-2023
A median, segmented, annelid nerve cord has repeatedly been compared to the arthropod and vertebrate cords became most used textbook representation of nervous system. Recent phylogenomic analyses, however, challenge hypothesis that a subepidermal rope-ladder-like ventral (VNC) composed paired serial chain ganglia somata-free connectives represents either plesiomorphic or typical condition in annelids. Using comparative approach by combining analyses with morphological methods...
Abstract Drug combination therapies for cancer treatment show high efficacy but often induce severe side effects, resulting in dose or cycle number reduction. We investigated the impact of neoadjuvant chemotherapy (neoCTx) adaptions on outcome 59 patients with pancreatic ductal adenocarcinoma (PDAC). Resections tumor‐free margins were significantly more frequent when full‐dose neoCTx was applied. determined if patient‐derived organoids (PDOs) can be used to personalize poly‐chemotherapy...
Targeted therapies are effective in treating cancer, but success depends on identifying cancer vulnerabilities. In our study, we utilize small RNA sequencing to examine the impact of pathway activation microRNA (miRNA) expression patterns. Interestingly, discover that miRNAs capable inhibiting key members activated pathways frequently diminished. Building this observation, develop an approach integrates a low-miRNA-expression signature identify druggable target genes cancer. We train and...
Abstract Myotonic dystrophy type 2 (DM2) is a tetranucleotide CCTG repeat expansion disease associated with an increased prevalence of autoimmunity. Here, we identified elevated I interferon (IFN) signature in peripheral blood mononuclear cells and primary fibroblasts DM2 patients as trigger chronic immune stimulation. Although RNA-repeat accumulation was prevalent the cytosol DM2-patient fibroblasts, type-I IFN release did not depend on innate RNA sensors but rather DNA sensor cGAS...
Venoms evolved convergently in diverse animal lineages as key adaptations that increase the evolu-tionary fitness of species which are manifold employed for defense, predation and competition. They constitute complex cocktails various toxins feature a broad range bioactivities. The majority described venom proteins belong to protein families known comprise housekeeping genes or harbor protein-domains, present with non-venom related functions. However, evolutionary processes mechanisms foster...
Germline variants that disrupt components of the epigenetic machinery cause syndromic neurodevelopmental disorders. Using exome and genome sequencing, we identified de novo in KDM2A , a lysine demethylase crucial for embryonic development, 18 individuals with developmental delays and/or intellectual disabilities. The severity ranged from learning disabilities to severe disability. Other core symptoms included feeding difficulties, growth issues such as intrauterine restriction, short stature...
Predatory robber flies (Diptera, Asilidae) have been suspected to be venomous due their ability overpower well-defended prey. However, details of venom composition and toxin arsenal remained unknown. Here, we provide a detailed characterization the system through application comparative transcriptomics, proteomics functional morphology. Our results reveal asilid venoms dominated by peptides non-enzymatic proteins, that majority components in crude is represented just ten families, which...
Abstract Objectives We analysed whether temporal heterogeneity of ctDNA encodes evolutionary patterns in ovarian cancer. Methods Targeted sequencing 275 cancer-associated genes was performed a primary tumor biopsy and six longitudinal plasma samples from 15 patients, using the Illumina platform. Results While there low overall concordance between mutational spectrum biopsies vs. ctDNA, TP53 variants were most commonly shared somatic alterations. Up to three variant clusters detected each...
Venoms and the toxins they contain represent molecular adaptations that have evolved on numerous occasions throughout animal kingdom. However, processes shape venom protein evolution are poorly understood because of scarcity whole-genome data available for comparative analyses venomous species.We performed a broad toxicogenomic analysis to gain insight into genomic mechanisms in robber flies (Asilidae). We first sequenced high-quality draft genome hymenopteran hunting fly Dasypogon diadema,...
We present the first molecular characterization of glycerotoxin (GLTx), a potent neurotoxin found in venom bloodworm Glycera tridactyla (Glyceridae, Annelida). Within animal kingdom, GLTx shows unique mode action as it can specifically up-regulate activity Cav2.2 channels (N-type) reversible manner. The lack sequence information has so far hampered detailed understanding its action. Our analyses reveal three ~3.8 kb full-length transcripts, show that represents multigene family, and suggest...
Breast cancer is a heterogeneous disease and the mechanistic framework for differential osteotropism among intrinsic breast subtypes unknown. Hypothesizing that cell morphology could be an integrated readout functional state of cell, we established catalogue migratory, molecular biophysical traits MDA-MB-231 cells, compared it with two enhanced bone-seeking derivative lines these findings single profiles. Such knowledge essential predicting metastatic capacities in cancer. High-resolution...
Single nucleotide polymorphisms are currently not considered in breast cancer (BC) risk predictions used daily practice of genetic counselling and clinical management familial BC Germany. This study aimed to assess the value incorporating a 313-variant-based polygenic score (PRS) into calculations cohort German women with suspected hereditary ovarian syndrome (HBOC). Data from 382 individuals seeking for HBOC were analysed. Risk performed using Breast Ovarian Analysis Disease Incidence...
Overcoming PARPi resistance is a high clinical priority. We established and characterized comparative in vitro models of acquired resistance, derived from either BRCA1-proficient or BRCA1-deficient isogenic background by long-term exposure to olaparib. While parental cell lines already exhibited certain level intrinsic activity multidrug (MDR) proteins, resulting PARPi-resistant cells both further converted toward MDR. In models, the phenotype was shaped (i) cross-resistance other PARPis...
The biochemical phenotype of paragangliomas (PGLs) is highly dependent on the underlying genetic background and tumor location. PGLs at extra-adrenal locations usually do not express phenylethanolamine N-methyltransferase (PNMT), enzyme required for epinephrine production, which was explained by absence glucocorticoids. with pathogenic variants (PVs) in Harvey rat sarcoma viral oncogene homolog (HRAS) can occur or outside adrenal, but always synthesize independently localization. Here, we...
Pheochromocytomas and paragangliomas (PCCs/PGLs) are catecholamine-producing tumors.In inoperable metastatic cases, somatostatin type 2 receptor (SSTR2) expression allows for peptide radionuclide therapy with [ 177 Lu]Lu-DOTA-TATE.Insufficient levels, however, limit treatment efficacy.This study evaluates whether the epigenetic drugs valproic acid (VPA) 5-Aza-2'-deoxycytidine (DAC) modulate SSTR2 levels sensitivity to Lu]Lu-DOTA-TATE in two mouse PCC models (MPC MTT).Methods: Drug-effects on...
To optimize neoadjuvant radiochemotherapy of pancreatic ductal adenocarcinoma (PDAC), the value new irradiation modalities such as proton therapy needs to be investigated in relevant preclinical models. We studied individual treatment responses RCT using patient-derived PDAC organoids (PDO). Four PDO lines were treated with gemcitabine, 5-fluorouracile (5FU), photon and combined RCT. Therapy response was subsequently measured via viability assays. In addition, treatment-naive PDOs...
Continuous activation of hypoxia pathways in pheochromocytomas and paragangliomas (PPGLs) is associated with higher disease aggressiveness, for which effective treatment strategies are still missing. Most the commonly used vitro models lack characteristics these pseudohypoxic tumors, including elevated expression hypoxia-inducible factor (HIF) 2α. To address this shortcoming, we investigated whether recurrent cycles lead to continuous under normoxic conditions pseudohypoxia increased...
Abstract A median, segmented, annelid nerve cord has repeatedly been compared to the arthropod and vertebrate cords became most used textbook representation of nervous system. Recent phylogenomic analyses, however, challenge hypothesis that a subepidermal rope-ladder-like ventral (VNC) composed paired serial chain ganglia somata-free connectives represents neither plesiomorphic nor typical condition in annelids. Using comparative approach by combining analyses with morphological methods...
Abstract Considering polygenic risk scores (PRSs) in individual prediction is increasingly implemented genetic testing for hereditary breast cancer (BC) based on next-generation sequencing (NGS). To calculate BC risks, the Breast and Ovarian Analysis of Disease Incidence Carrier Estimation Algorithm (BOADICEA) with inclusion BCAC 313 or BRIDGES 306 PRS commonly used. The calculation depends accurately reproducing variant allele frequencies (AFs) and, consequently, distribution values...
Radiation-induced morphea (RIM) is a rare complication of radiotherapy presenting as inflammatory fibrosis, most commonly reported in breast cancer patients. As underlying disease mechanisms are not well understood, targeted therapies lacking. Since fibroblasts the key mediators all fibroproliferative diseases, this study aimed to characterize patient-derived identify therapeutic targets. We studied primary human control and RIM-fibroblasts on functional molecular basis, analyzed peripheral...
Uniparental disomy (UPD) is the inheritance of both alleles a chromosome from only one parent. So far, detection UPDs in sequencing data not well established and known gap next-generation (NGS) diagnostics. By developing new tool for UPD detection, we re-evaluated an eight-year-old individual presenting with scoliosis, muscle weakness global developmental delay. Previous panel analysis identified homozygous likely pathogenic loss-of-function variant
Abstract Nucleic acid accumulation in repeat expansion disease poses multiple challenges to cellular integrity. Myotonic dystrophy type 2 (DM2) results from large CCTG repeats the CNBP gene leading myopathy and an increased prevalence of autoimmunity. Here, we observed that DM2 patients exhibited a type-I interferon signature blood cultured fibroblasts. RNA was prevalent cytosol patient fibroblasts, facilitating repeat-associated non-AUG translation. The ensuing chronic endoplasmic reticulum...