A5030727249- Extracellular vesicles in disease
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Renal and related cancers
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- CAR-T cell therapy research
- Circular RNAs in diseases
- Cancer, Lipids, and Metabolism
- Cancer Genomics and Diagnostics
- Lipid metabolism and biosynthesis
- Nanofabrication and Lithography Techniques
- T-cell and B-cell Immunology
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- RNA regulation and disease
- Mycobacterium research and diagnosis
University of Würzburg
2021-2024
Universitätsklinikum Würzburg
2019
T cell-engaging immunotherapies are changing the landscape of current cancer care. However, suitable target antigens scarce, restricting these strategies to very few tumor types. Here, we report on a antibody derivative that comes in two complementary halves and addresses antigen combinations instead single molecules. Each half, now coined hemibody, contains an antigen-specific single-chain variable fragment (scFv) fused either light (VL) or heavy (VH) chain domain anti-CD3 antibody. When...
SREBP2 is a master regulator of the mevalonate pathway (MVP), biosynthetic process that drives synthesis dolichol, heme A, ubiquinone and cholesterol also provides substrates for protein prenylation. Here, we identify as novel substrate USP28, deubiquitinating enzyme frequently upregulated in squamous cancers. Our results show silencing USP28 reduces expression MVP enzymes lowers metabolic flux into this pathway. We binds to mature SREBP2, leading its deubiquitination stabilisation....
Abstract In pancreatic ductal adenocarcinoma (PDAC), endogenous MYC is required for S-phase progression and escape from immune surveillance. Here we show that in PDAC cells needed the recruitment of PAF1c transcription elongation complex to RNA polymerase depletion CTR9, a subunit, enables long-term survival PDAC-bearing mice. largely dispensable normal proliferation regulation target genes. Instead, limits DNA damage associated with by being essential expression long genes involved...
Abstract Deregulated expression of the MYC oncoprotein enables tumor cells to evade immune surveillance, but mechanisms underlying this surveillance are poorly understood. We show here that endogenous protects pancreatic ductal adenocarcinoma (PDAC) driven by KRASG12D and TP53R172H from eradication system. Deletion TANK-binding kinase 1 (TBK1) bypassed requirement for high expression. TBK1 was active due accumulation double-stranded RNA (dsRNA), which derived inverted repetitive elements...
Pancreatic ductal adenocarcinoma remains a major challenge in cancer medicine. Given the increase incidence and mortality, interdisciplinary research is necessary to translate basic knowledge into therapeutic strategies improving outcome of patients. On 4
In response to perturbed transcription elongation, the MYC oncoprotein multimerizes and undergoes a phase transition; underlying mechanisms their function are unknown. Here, we show that re-localizes from its canonical location on DNA RNA in accumulation of intronic RNA. binds directly, which enhances multimerization. multimers concentrate nuclear exosome, 3'-5' exonuclease, targeting complexes around double-stranded R-loops, promote exosome recruitment R-loops. binding suppresses activation...
<p>Characterization of MYC depletion.</p>
<p>Characterization of MYC depletion.</p>
<p>Role of MIZ1 in gene regulation.</p>
<p>Characterization of dsRNA and ssDNA in KPC cells.</p>
<p>Further characterization of dsRNA species.</p>
<p>Characterization of MYC depletion.</p>
<p>Histological analyses of transplanted tumors.</p>
<p>TBK1-dependent regulation of NF-kB-dependent gene expression.</p>
<p>Characterization of MYC depletion.</p>
<p>Histological analyses of transplanted tumors.</p>
<p>Further characterization of dsRNA species.</p>
<p>Characterization of dsRNA and ssDNA in KPC cells.</p>
<p>Role of MIZ1 in gene regulation.</p>
<p>TBK1-dependent regulation of NF-kB-dependent gene expression.</p>
<div>Abstract<p>Deregulated expression of the MYC oncoprotein enables tumor cells to evade immune surveillance, but mechanisms underlying this surveillance are poorly understood. We show here that endogenous protects pancreatic ductal adenocarcinoma (PDAC) driven by KRAS<sup>G12D</sup> and TP53<sup>R172H</sup> from eradication system. Deletion TANK-binding kinase 1 (TBK1) bypassed requirement for high expression. TBK1 was active due accumulation...
<div>Abstract<p>Deregulated expression of the MYC oncoprotein enables tumor cells to evade immune surveillance, but mechanisms underlying this surveillance are poorly understood. We show here that endogenous protects pancreatic ductal adenocarcinoma (PDAC) driven by KRAS<sup>G12D</sup> and TP53<sup>R172H</sup> from eradication system. Deletion TANK-binding kinase 1 (TBK1) bypassed requirement for high expression. TBK1 was active due accumulation...
<p>Characterization of MYC function in KPC cells.</p>