A5035543427- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- Cancer Cells and Metastasis
- Immunotherapy and Immune Responses
- Extracellular vesicles in disease
- RNA and protein synthesis mechanisms
- Ovarian cancer diagnosis and treatment
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Microtubule and mitosis dynamics
- Bioinformatics and Genomic Networks
- Connective tissue disorders research
- Dermatology and Skin Diseases
- Food Allergy and Anaphylaxis Research
- CRISPR and Genetic Engineering
- Cancer, Hypoxia, and Metabolism
- Cancer Mechanisms and Therapy
- vaccines and immunoinformatics approaches
- Effects and risks of endocrine disrupting chemicals
- Melanoma and MAPK Pathways
- Fungal Infections and Studies
- Fungal and yeast genetics research
- Platelet Disorders and Treatments
- Lung Cancer Treatments and Mutations
- RNA Research and Splicing
National Center for Tumor Diseases
2017-2024
German Cancer Research Center
2017-2024
Heidelberg University
2017-2024
University Hospital Carl Gustav Carus
2018-2024
TU Dresden
2018-2024
Zimmer Biomet (Germany)
2022-2024
Deutschen Konsortium für Translationale Krebsforschung
2022
Nationales Centrum für Tumorerkrankungen Dresden
2022
Institute of Pharmacology
2021
Helmholtz-Zentrum Dresden-Rossendorf
2020
Objective Gastric cancer is the second leading cause of cancer-related deaths and fifth most common malignancy worldwide. In this study, human mouse gastric organoids were generated to model disease perform drug testing delineate treatment strategies. Design Human organoid cultures established, samples classified according their molecular profile response conventional chemotherapeutics tested. Targeted was performed specific druggable mutations. Mouse carrying subtype-specific alterations....
Alternative splicing (AS) is a cellular process that increases cell's coding capacity from limited set of genes.Although AS common in higher plants and animals, its prevalence other eukaryotes mostly unknown.In fungi the involvement gene expression effect on multi-cellularity virulence great medical economic interest.We present genome-wide comparative study 23 informative different taxa, based alignments public transcript sequences.Random sampling expressed sequence tags allows for robust...
Prenatal and early postnatal exposures to environmental factors are considered responsible for the increasing prevalence of allergic diseases. Although there is some evidence allergy-promoting effects in children because exposure plasticizers, such as phthalates, findings previous studies inconsistent lack mechanistic information.We investigated effect maternal phthalate on asthma development subsequent generations their underlying mechanisms, including epigenetic alterations.Phthalate...
Article24 March 2016Open Access Transparent process Environment-induced epigenetic reprogramming in genomic regulatory elements smoking mothers and their children Tobias Bauer orcid.org/0000-0002-4961-3639 Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany Search for more papers by this author Saskia Trump Department Environmental Immunology, Helmholtz Centre Leipzig - UFZ, Leipzig, Naveed Ishaque Heidelberg Personalized Oncology, DKFZ-HIPO,...
Exposure to endocrine-disrupting chemicals can alter normal physiology and increase susceptibility non-communicable diseases like obesity. Especially the prenatal early postnatal period is highly vulnerable adverse effects by environmental exposure, promoting developmental reprogramming epigenetic alterations. To obtain a deeper insight into role of bisphenol A (BPA) exposure in children's overweight development, we combine epidemiological data with experimental models BPA-dependent DNA...
Abstract Lactate is a central metabolite in brain physiology but also contributes to tumor development. Glioblastoma (GB) the most common and malignant primary adults, recognized by angiogenic invasive growth, addition its altered metabolism. We show herein that lactate fuels GB anaplerosis replenishing tricarboxylic acid (TCA) cycle absence of glucose. dehydrogenases (LDHA LDHB), which we found spatially expressed tissues, catalyze interconversion pyruvate lactate. However, ablation both...
Abstract Systemic pan-tumor analyses may reveal the significance of common features implicated in cancer immunogenicity and patient survival. Here, we provide a comprehensive multi-omics data set for 32 patients across 25 tumor types proteogenomic-based discovery neoantigens. By using an optimized computational approach, discover large number tumor-specific tumor-associated antigens. To create pipeline identification neoantigens our cohort, combine DNA RNA sequencing with MS-based...
The prognosis of pancreatic ductal adenocarcinoma (PDAC) is one the most dismal all cancers and median survival PDAC patients only 6-8 months after diagnosis. While decades research effort have been focused on early diagnosis understanding molecular mechanisms, few clinically useful markers universally applied. To improve treatment management PDAC, it equally relevant to identify prognostic factors for optimal therapeutic decision-making patient survival. Compelling evidence suggested...
Cholangiocarcinoma (CC) is an aggressive malignancy with inferior prognosis due to limited systemic treatment options. As preclinical models such as CC cell lines are extremely rare, this manuscript reports a protocol of cholangiocarcinoma patient-derived organoid culture well for the transition 3D 2D lines. Tissue samples non-cancer bile duct and were obtained during surgical resection. Organoid generated following standardized protocol. from established novel Subcutaneous orthotopic...
Abstract Germline mutations in the ubiquitously expressed ACTB , which encodes β-cytoplasmic actin (CYA), are almost exclusively associated with Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF). Here, we report six patients previously undescribed heterozygous variants clustered 3′-coding region of . Patients present clinical features distinct from BWCFF, including mild developmental disability, microcephaly, and thrombocytopenia platelet anisotropy. Using patient-derived fibroblasts,...
Abstract Background Extensive local invasion of glioblastoma (GBM) cells within the central nervous system (CNS) is one factor that severely limits current treatments. The aim this study was to uncover genes involved in process, which could also serve as therapeutic targets. For isolation invasive GBM from non-invasive cells, we used a three-dimensional organotypic co-culture where glioma stem cell (GSC) spheres were confronted with brain organoids (BOs). Using ultra-low input RNA sequencing...
Abstract Background Clear cell renal carcinoma (ccRCC) is the most common subtype of RCC with high rates metastasis. Targeted therapies such as tyrosine kinase and checkpoint inhibitors have improved treatment success, but therapy-related side effects tumor recurrence remain a challenge. As result, ccRCC still mortality rate. Early detection before metastasis has great potential to improve outcomes, no suitable biomarker specific for available so far. Therefore, molecular biomarkers derived...
With the introduction of Olaparib treatment for BRCA-deficient recurrent ovarian cancer, testing somatic and/or germline mutations in BRCA1/2 genes tumor tissues became essential decisions. In most cases only formalin-fixed paraffin-embedded (FFPE) samples, containing fragmented and chemically modified DNA minor quality, are available. Thus, multiplex PCR-based sequencing is commonly applied routine molecular testing, which predominantly focused on identification known hot spot oncogenes. We...
Rationale: Fibrosis promotes the maintenance of atrial fibrillation (AF), making it resistant to therapy. Improved understanding molecular mechanisms leading fibrosis will open new pathways toward effective antifibrotic therapies. Objective: This study aims decipher mechanistic interplay between PLK2 (polo-like kinase 2) and profibrotic cytokine OPN (osteopontin) in pathogenesis AF. Methods Results: Atrial mRNA expression was 10-fold higher human fibroblasts than cardiomyocytes. Compared...
Abstract Veraison marks the transition from berry growth to ripening and is a crucial phenological stage in grapevine (Vitis vinifera): berries become soft begin accumulate sugars, aromatic substances, and, red cultivars, anthocyanins for pigmentation, while organic acid levels decrease. These changes determine potential quality of wine. However, rising global temperatures lead earlier flowering ripening, which strongly influence wine quality. Here, we combined genotyping-by-sequencing with...
Abstract Melanomas frequently metastasize to distant organs and especially intracranial metastases still represent a major clinical challenge. Epigenetic reprogramming of is thought be involved in therapy failure, but so far only little known about patient-specific DNA-methylation differences between intra- extracranial melanoma metastases. Hierarchical clustering the methylomes 24 patient-matched pairs revealed that individual patients were more similar each other than same tissue from...
Despite remarkable advances in treating patients with metastatic melanoma, management of melanoma brain metastases remains challenging. Recent evidence suggests that epigenetic reprogramming is an important mechanism for the adaptation cells to environment. In this study, methylomes and transcriptomes a cohort matched were evaluated by integrated omics data analysis. The identified 38 candidate genes displayed distinct promoter methylation corresponding gene expression changes intracranial...
Melanoma, the deadliest form of skin cancer, can metastasize to different organs. Molecular differences between brain and extracranial melanoma metastases are poorly understood. Here, promoter methylation gene expression 11 heterogeneous patient-matched pairs were analyzed using melanoma-specific regulatory networks learned from public transcriptome methylome data followed by network-based impact propagation patient-specific alterations. This innovative analysis strategy allowed predict...
Abstract Melanoma is the most serious type of skin cancer that frequently spreads to other organs human body. Especially melanoma metastases brain (intracranial metastases) are hard treat and a major cause death patients. Little known about molecular alterations altered mechanisms distinguish intra- from extracranial metastases. So far, almost all existing studies compared intracranial one set patients an another This neglects important facts each highly individual same patient more similar...
The IDH1R132H mutation in glioma results the neoenzymatic function of IDH1, leading to production oncometabolite 2-hydroxyglutarate (2-HG), alterations energy metabolism and changes cellular redox household. Although shifts ratio NADPH/NADP+ were described, consequences for NAD+ synthesis pathways potential therapeutic interventions largely unexplored. Here, we describe effects heterozygous on system a CRISPR/Cas edited glioblastoma model compare them with IDH1 wild-type (IDH1wt) cells....
// Sarah Schott 1, 2, 3, * , Pauline Wimberger 4, 5, Barbara Klink 6 Konrad Grützmann 5 Julian Puppe 7 Ulrike Sophie Wauer Daniel Martin Klotz Evelin Schröck and Jan Dominik Kuhlmann 1 Department of Gynecology Obstetrics, University Hospital Heidelberg, Germany 2 German Cancer Consortium (DKTK), Dresden Research Center (DKFZ), 3 National for Tumor Diseases (NCT), 4 Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Partner Site Institute Clinical Genetics, Medicine Cologne,...