A5001444848- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Neuroendocrine Tumor Research Advances
- Epigenetics and DNA Methylation
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Chromatin Remodeling and Cancer
- Kruppel-like factors research
- Cancer Cells and Metastasis
- Genetic Syndromes and Imprinting
- Pancreatic function and diabetes
- Cancer-related gene regulation
- Microtubule and mitosis dynamics
- Histone Deacetylase Inhibitors Research
- Cancer Research and Treatments
- Lung Cancer Research Studies
- Cancer-related Molecular Pathways
- Protein Degradation and Inhibitors
- Genomics and Chromatin Dynamics
- Heat shock proteins research
- RNA modifications and cancer
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Phagocytosis and Immune Regulation
- DNA Repair Mechanisms
- Ferroptosis and cancer prognosis
Universitätsmedizin Göttingen
2016-2025
University of Göttingen
2014-2022
University Medical Center Hamburg-Eppendorf
2012-2016
Universität Hamburg
2012-2016
Leibniz Institute of Virology (LIV)
2009-2015
Eppendorf (Germany)
2014
University Cancer Center Hamburg
2014
Abstract Alzheimer's disease is a common neurodegenerative, progressive, and fatal disorder. Generation deposition of amyloid beta (Aβ) peptides associate with its pathogenesis small soluble Aβ oligomers show the most pronounced neurotoxic effects correlate initiation progression. Recent findings showed that bind to cellular prion protein (PrP C ) eliciting effects. The role exosomes, extracellular vesicles endosomal origin, in only poorly understood. Besides serving as biomarkers they may...
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with particularly dismal prognosis. Histone deacetylases (HDAC) are epigenetic modulators whose activity frequently deregulated in various cancers including PDAC. In particular, class-I HDACs (HDAC 1, 2, 3 and 8) have been shown to play an important role this study, we investigated the effects of class I-specific HDAC inhibitor (HDACi) 4SC-202 multiple PDAC cell lines promoting tumor differentiation. We show that...
ARID1A (AT-rich interactive domain-containing protein 1A) is a subunit of the BAF chromatin remodeling complex and plays roles in transcriptional regulation DNA damage response. Mutations that lead to inactivation or loss expression are frequent widespread across many cancer types including colorectal (CRC). A tumor suppressor role has been established number CRC where genetic Arid1a alone led formation invasive adenocarcinomas mice. Mechanistically, described largely function through...
Abstract Cancer cells must develop strategies to adapt the dynamically changing stresses caused by intrinsic or extrinsic processes, therapeutic agents. Metabolic adaptability is crucial mitigate such challenges. Considering metabolism as a central node of adaptability, it focused on an energy sensor, AMP‐activated protein kinase (AMPK). In subtype pancreatic ductal adenocarcinoma (PDAC) elevated AMPK expression and phosphorylation identified. Using drug repurposing that combined screening...
Disruptor of telomeric silencing 1-like (DOT1L) is a non-SET domain containing methyltransferase known to catalyze mono-, di-, and tri-methylation histone 3 on lysine 79 (H3K79me). DOT1L-mediated H3K79me has been implicated in chromatin-associated functions including gene transcription, heterochromatin formation, DNA repair. Recent studies have uncovered role for DOT1L the initiation progression leukemia other solid tumors. The development availability small molecule inhibitors may provide...
Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because this association, it commonly assumed H2Bub1 an exclusively positively acting and increased occupancy correlates with gene expression. In contrast, depletion the ubiquitin ligases RNF20 or RNF40 alters expression only subset genes. Using conditional Rnf40 knockout mouse embryo fibroblasts, we show genes occupied by low moderate amounts are selectively...
TGFβ-SMAD signaling exerts a contextual effect that suppresses malignant growth early in epithelial tumorigenesis but promotes metastasis at later stages. Longstanding challenges resolving this functional dichotomy may uncover new strategies to treat advanced carcinomas. The Krüppel-like transcription factor, KLF10, is pivotal effector of TGFβ/SMAD mediates antiproliferative effects TGFβ. In study, we show how KLF10 opposes the prometastatic TGFβ by limiting its ability induce...
Abstract Background Basal-like breast cancer (BLBC) is one of the most aggressive malignant diseases in women with an increased metastatic behavior and poor prognosis compared to other molecular subtypes cancer. Resistance chemotherapy main cause treatment failure BLBC. Therefore, novel therapeutic strategies counteracting gain aggressiveness underlying therapy resistance are urgently needed. The epithelial-to-mesenchymal transition (EMT) has been established as central process stimulating...
Abstract As a member of the 11-gene “death-from-cancer” gene expression signature, overexpression Ubiquitin-Specific Protease 22 ( USP22 ) was associated with poor prognosis in various human malignancies. To investigate function cancer development and progression, we sought to detect common USP22-dependent molecular mechanisms colorectal breast cell lines. We performed mRNA-seq compare profiles (SW837, SW480, HCT116) mammary (HCC1954 MCF10A) lines upon siRNA-mediated knockdown USP22....
The cellular prion protein (PrPC) is a cell surface glycoprotein attached to the membrane by glycosylphosphatidylinositol (GPI)-anchor and plays critical role in transmissible, neurodegenerative fatal diseases. Alterations attachment influence PrPC-associated signaling, development of disease, yet our knowledge GPI-anchor localization, processing, function PrPC vivo limited We exchanged signal sequence for that Thy-1 (PrPCGPIThy-1) cells mice. show this modifies composition, which then lacks...
Abstract The Ubiquitin-Specific Protease 22 (USP22) is a deubiquitinating subunit of the mammalian SAGA transcriptional co-activating complex. USP22 was identified as member so-called “death-from-cancer” signature predicting therapy failure in cancer patients. However, importance and functional role different types subtypes remain largely unknown. In present study, we leveraged human cell lines genetic mouse models to investigate HER2-driven breast (HER2 + -BC) demonstrate for first time...
Cellular differentiation is accompanied by dramatic changes in chromatin structure which direct the activation of lineage-specific transcriptional programs. Structure-specific recognition protein-1 (SSRP1) a histone chaperone important for chromatin-associated processes such as transcription, DNA replication and repair. Since function SSRP1 during cell remains unclear, we investigated its potential role controlling lineage determination. Depletion human mesenchymal stem cells elicited...
Bromodomain-containing protein 4 (BRD4) is a member of the bromo- and extraterminal (BET) domain-containing family epigenetic readers which under intensive investigation as target for anti-tumor therapy. BRD4 plays central role in promoting expression select subsets genes including many driven by oncogenic transcription factors signaling pathways. However, effects BET inhibitors non-transformed cells remain mostly unclear. We demonstrate that required maintenance basal epithelial phenotype...
Abstract Background Breast cancer (BC) is the most frequent tumor entity in women worldwide with a high chance of therapeutic response early- and non-metastatic disease stages. Among all BC subtypes, triple-negative (TNBC) challenging subtype lacking effective molecular targets due to particular enrichment stem cells (CSCs), frequently leading chemoresistant phenotype metastasis. The Ubiquitin Specific Peptidase 22 (USP22) deubiquitinase that has been associated CSC-promoting function...
Abstract The stress-associated chaperone system is an actionable target in cancer therapies. It ubiquitously upregulated tissues and enables tumorigenicity by stabilizing oncoproteins. Most inhibitors the key component, heat-shock protein 90 (HSP90). Although HSP90 are highly tumor-selective, they fail clinical trials. These failures partly due to interference with a negative regulatory feedback loop response (HSR): inhibition, there compensatory synthesis of stress-inducible chaperones,...
Simian virus 40 (SV40) is a powerful tool to study cellular transformation in vitro, as well tumor development and progression vivo. Various kinases, among them members of the CK1 family, play an important role modulating transforming activity SV40, including T-Ag, major protein itself. Here we characterized effects mutant CK1δ variants with impaired kinase on SV40-induced cell mammary carcinogenesis vivo transgenic/bi-transgenic mouse model. mutants exhibited reduced compared wtCK1δ vitro...
// Robyn L. Kosinsky 1, 2 , Florian Wegwitz 1 Nicole Hellbach 3 Matthias Dobbelstein Ahmed Mansouri 4 Tanja Vogel Yvonne Begus-Nahrmann 2, * Steven A. Johnsen Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, 37075 Germany Institute Molecular Oncology, Göttingen Biosciences (GZMB), Faculty Medicine, 37077 Embryology, Anatomy Cell Biology, Freiburg, 79104 Max-Planck for Biophysical Chemistry, RG Differentiation, These authors have contributed equally...
Abstract Background and Aims Inflammatory bowel diseases are linked to an increased risk of developing colorectal cancer [CRC]. Previous studies suggested that the H2B ubiquitin ligase RING finger protein-20 [RNF20] inhibited inflammatory signaling mediated by nuclear factor kappa-light-chain-enhancer activated B cells [NF-κB]. However, role RNF40, obligate heterodimeric partner RNF20, in context inflammation CRC has not been addressed. Here, we examined effect RNF40 loss on vitro vivo....
Schwann cells are the nerve ensheathing of peripheral nervous system. Absence, loss and malfunction or their myelin sheaths lead to neuropathies such as Charcot-Marie-Tooth disease in humans. During cell development myelination chromatin is dramatically modified. However, impact functional relevance these modifications poorly understood. Here, we analyzed histone H2B monoubiquitination one modification by conditionally deleting Rnf40 subunit responsible E3 ligase mice. Rnf40-deficient were...
The vast majority of human tumors with p53 mutations undergo loss the remaining wildtype allele (loss-of-heterozygosity, p53LOH). p53LOH has watershed significance in promoting tumor progression. However, driving forces for are poorly understood. Here we identify repressive WTp53-HSF1 axis as one driver p53LOH. We find that WTp53 AOM/DSS chemically-induced colorectal (CRC) p53R248Q/+ mice retains partial activity and represses heat-shock factor 1 (HSF1), master regulator proteotoxic stress...