A5064034814- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- CAR-T cell therapy research
- Pluripotent Stem Cells Research
- Peptidase Inhibition and Analysis
- Marine Sponges and Natural Products
- Plant-based Medicinal Research
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Cells and Metastasis
- Lymphoma Diagnosis and Treatment
- Gene expression and cancer classification
- Bacteriophages and microbial interactions
- Chromosomal and Genetic Variations
- Viral-associated cancers and disorders
- Algorithms and Data Compression
- Genetic Neurodegenerative Diseases
Technical University of Munich
2014-2023
Molecular Oncology (United States)
2023
Genomics (United Kingdom)
2023
The Francis Crick Institute
2020
Heidelberg University
2015-2017
Klinikum rechts der Isar
2014-2017
German Cancer Research Center
1978-2017
Universitätsklinikum Erlangen
2017
Friedrich-Alexander-Universität Erlangen-Nürnberg
2017
University of Amsterdam
1997
Abstract Although mutations may represent attractive targets for immunotherapy, direct identification of mutated peptide ligands isolated from human leucocyte antigens (HLA) on the surface native tumour tissue has so far not been successful. Using advanced mass spectrometry (MS) analysis, we survey melanoma-associated immunopeptidome to a depth 95,500 patient-presented peptides. We thereby discover large spectrum target antigen candidates including cancer testis and phosphopeptides. Most...
Here, we show CRISPR/Cas9-based targeted somatic multiplex-mutagenesis and its application for high-throughput analysis of gene function in mice. Using hepatic single guide RNA (sgRNA) delivery, large sets to induce hepatocellular carcinoma (HCC) intrahepatic cholangiocarcinoma (ICC). We observed Darwinian selection target genes, which suppress tumorigenesis the respective cellular/tissue context, such as Pten or Cdkn2a, conversely found low frequency Brca1/2 alterations, explaining...
Mouse transgenesis has provided fundamental insights into pancreatic cancer, but is limited by the long duration of allele/model generation. Here we show transfection-based multiplexed delivery CRISPR/Cas9 to pancreas adult mice, allowing simultaneous editing multiple gene sets in individual cells. We use method induce cancer and exploit mutational signatures for phylogenetic tracking metastatic disease. Our results demonstrate that CRISPR/Cas9-multiplexing enables key applications, such as...
In addition to locally controlling the tumor, hypofractionated radiotherapy (RT) particularly aims activate immune cells in RT-modified microenvironment. Therefore, we examined whether RT can dendritic (DCs), induce cell infiltration tumors, and how chronology of migration into tumors occurs gain knowledge for future definition radiation breaks inclusion immunotherapy. Colorectal cancer treatments offer only limited survival benefit, immunobiological principles additional therapies need be...
Abstract B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe PiggyBac transposon tools and mouse models for recessive screening show their application to study clonal lymphomagenesis. In a genome-wide screen, discover related diverse molecular processes, including signaling, transcriptional regulation, chromatin or RNA metabolism....
Abstract SUMOylation is a post-translational modification of proteins that regulates these proteins’ localization, turnover or function. Aberrant frequently found in cancers but its origin remains elusive. Using genome-wide transposon mutagenesis screen MYC-driven B-cell lymphoma model, we here identify the SUMO isopeptidase (or deconjugase) SENP6 as tumor suppressor links unrestricted to development and progression. Notably, recurrently deleted human lymphomas deficiency results...
Abstract Small cell lung cancer (SCLC) is a highly aggressive type of cancer, characterized by rapid proliferation, early metastatic spread, clinical recurrence and high rate mortality. Using in vivo insertional mutagenesis screening conjunction with cross-species genomic transcriptomic validation, we identified strong consistent signal for neuronal, synaptic, glutamatergic signaling gene sets murine human SCLC. We show that SCLC cells have the ability to develop intimate contacts neuronal...
To investigate relations between clinical and neuropathological features age of onset, presence anticipation, genetic linkage in autosomal dominant cerebellar ataxia type II (ADCA II).The natural history ADCA was studied on the basis findings two pedigrees studies were carried out with polymorphic DNA markers largest, four generation, pedigree.Ataxia constant all groups. Retinal degeneration early extinction electroretinogram constituted an important component juvenile adult (< 25 years)...
The molecular carcinogenesis of intraductal tubulopapillary neoplasms (ITPN), recently described as rare in the pancreato-biliary tract with a favorable prognosis despite high incidence associated adenocarcinoma, is still poorly understood. To identify driver genes, chromosomal gains and losses, mutational signatures, key signaling pathways, potential therapeutic targets, profile 11 biliary 6 pancreatic ITPNs, invasive adenocarcinoma 14/17 cases, are studied by whole exome sequencing (WES)....
In contrast to mono- or biallelic loss of tumor-suppressor function, effects discrete gene dysregulations, as caused by non-coding (epi)genome alterations, are poorly understood. Here, perturbing the regulatory genome in mice, we uncover pervasive roles subtle expression variation cancer evolution. Genome-wide screens characterizing 1,450 tumors revealed that such quasi-insufficiency is extensive across entities and displays diverse context dependencies, distinct cell-of-origin associations...
The p53 tumor suppressor protein is a potent activator of proliferative arrest and cell death. In normal cells, this pathway restrained by degradation mediated the E3-ubiquitin ligase activity MDM2. Oncogenic stress releases from MDM2 control, so activating response. However, many tumors that retain wild-type inappropriately maintain MDM2-p53 regulatory loop in order to continuously suppress activity. We have shown previously single point mutations human RING finger domain prevent...
We have recently performed a whole-body, genome-wide screen in mice using single-copy inactivating transposon for the identification of Pten (phosphatase and tensin homolog)-cooperating tumor suppressor genes (TSGs). identified known putative TSGs multiple cancer types validated functional clinical relevance several promising candidates human prostate cancer.
Transposon screens are powerful in vivo assays used to identify loci driving carcinogenesis. These identified as Common Insertion Sites (CISs), i.e. regions with more transposon insertions than expected by chance. However, the identification of CISs is affected biases insertion behaviour systems. Here, we introduce Transmicron, a novel method that differs from previous methods (i) modelling neutral rates based on chromatin accessibility, transcriptional activity and sequence context (ii)...