A5003448975- MicroRNA in disease regulation
- Pancreatic and Hepatic Oncology Research
- Cardiomyopathy and Myosin Studies
- Signaling Pathways in Disease
- RNA modifications and cancer
- Educational Curriculum and Learning Methods
- Immunotherapy and Immune Responses
- Circular RNAs in diseases
- Glioma Diagnosis and Treatment
- Cardiac Fibrosis and Remodeling
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Estrogen and related hormone effects
- Multiple Myeloma Research and Treatments
- Cardiac electrophysiology and arrhythmias
- Chromatin Remodeling and Cancer
- HER2/EGFR in Cancer Research
- CAR-T cell therapy research
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Cancer-related Molecular Pathways
- Cancer Cells and Metastasis
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
German Cancer Research Center
2016-2025
Heidelberg University
2016-2025
Deutschen Konsortium für Translationale Krebsforschung
2022-2025
Weizmann Institute of Science
2023
DKFZ-ZMBH Alliance
2004-2023
University Hospital Heidelberg
2009-2023
Imperial College London
2023
European Molecular Biology Laboratory
2023
University Hospital Ulm
2010-2012
University Hospital Schleswig-Holstein
2010-2012
The molecular pathogenesis of salivary gland acinic cell carcinoma (AciCC) is poorly understood. secretory Ca-binding phosphoprotein (SCPP) gene cluster at 4q13 encodes structurally related phosphoproteins which some are specifically expressed high levels in the glands and constitute major components saliva. Here we report on recurrent rearrangements [t(4;9)(q13;q31)] AciCC that translocate active enhancer regions from SCPP to region upstream Nuclear Receptor Subfamily 4 Group A Member 3...
Anticancer therapies have been limited by the emergence of mutations and other adaptations. In bacteria, antibiotics activate SOS response, which mobilizes error-prone factors that allow for continuous replication at cost mutagenesis. We investigated whether treatment lung cancer with EGFR inhibitors (EGFRi) similarly engages hypermutators. cycling drug-tolerant persister (DTP) cells in EGFRi-treated patients presenting residual disease, we observed upregulation GAS6, whereas ablation GAS6's...
Abstract Ribonucleoprotein complexes are dynamic assemblies of RNA with RNA-binding proteins, which modulate the fate RNA. Inversely, riboregulates interactions and functions associated proteins. Dysregulation ribonucleoprotein is linked to diseases such as cancer neurological disorders. In dividing cells, proteins present in mitotic structures, but their impact on cell division remains unclear. By applying proteome-wide R-DeeP strategy cells synchronized mitosis versus interphase integrated...
The composition of skeletal muscle, in terms the relative number slow- and fast-twitch fibers, is tightly regulated to enable an organism respond adapt changing physical demands. phosphatase calcineurin its downstream targets, transcription factors nuclear factor activated T cells (NFAT) family, play a critical role this process by promoting formation slow-twitch, oxidative fibers. Calcineurin binds calsarcins, family striated muscle-specific proteins sarcomeric Z-disc. We show here that...
Recent advances in cancer biology have emerged important roles for microRNAs (miRNAs) regulating tumor responses. However, their function mediating intercellular communication within the microenvironment is thus far poorly explored. Here, we found miR-206 to be abrogated human pancreatic ductal adenocarcinoma (PDAC) specimens and cell lines. We show that directly targets oncogenes KRAS annexin a2 (ANXA2), thereby acting as suppressor PDAC cells by blocking cycle progression, proliferation,...
Neoplasms with a myopericytomatous pattern represent morphological spectrum of lesions encompassing myopericytoma the skin and soft tissue, angioleiomyoma, myofibromatosis/infantile haemangiopericytoma putative neoplasms reported as malignant myopericytoma. Lack reproducible phenotypic genetic features myopericytic have prevented establishment sarcoma an acceptable diagnostic category. Following detection LMNA-NTRK1 gene fusion in index case paediatric haemangiopericytoma-like by combined...
Abstract Aggressive breast cancer is associated with poor patient outcome and characterized by the development of tumor cell variants that are able to escape from control immune system or resistant targeted therapies. The complex molecular mechanisms leading therapy resistance incompletely understood. We have previously shown high miR-519a-3p levels survival in cancer. Here, we demonstrate confers apoptosis induced TRAIL, FasL granzyme B/perforin interfering signaling cells. MiR-519a-3p...
Abstract Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. However, the determination of TM-interconnectivity in individual tumors is challenging impact on patient survival unresolved. Here, we establish connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) using dye uptake methodology, validate it recording cellular calcium epochs clinical correlations....
Activation of the phosphatase calcineurin and its downstream targets, transcription factors NFAT family, results in cardiomyocyte hypertrophy. Recently, it has been shown that dual specificity tyrosine (Y) phosphorylation-regulated kinase 1A (DYRK1A) is able to antagonize signaling by directly phosphorylating NFATs. We thus hypothesized DYRK1A might modulate hypertrophic response cardiomyocytes. In a model phenylephrine-induced hypertrophy, adenovirus-mediated overexpression DYKR1A...
Left ventricular non-compaction (LVNC) is caused by mutations in multiple genes. It still unclear whether LVNC the primary determinant of cardiomyopathy or rather a secondary phenomenon with intrinsic cardiomyocyte dysfunction being actual cause disease. Here, we describe family due to novel missense mutation, pE96K, cardiac troponin T gene (TNNT2). The mutation was identified index patient and all affected relatives, but not 430 healthy control individuals. Mutations known LVNC-associated...
Rationale: The emerging role of the ubiquitin–proteasome system in cardiomyocyte function and homeostasis implies necessity tight regulation protein degradation. However, little is known about cardiac components this machinery. Objective: We sought to determine whether molecules exist that control turnover cardiac-specific proteins. Methods Results: Using a bioinformatic approach identify novel cardiac-enriched sarcomere proteins, we identified F-box leucine-rich repeat 22 (Fbxl22)....
Epithelioid sarcoma (EpS) is a high-grade malignancy of unknown histogenesis first described in 1970 [1], characterized by high rates relapse and metastasis, with 5-year survival 60%-75% [2]. The only Food Drug Administration (FDA)-approved targeted therapy, the enhancer zeste homology 2 (EZH2) inhibitor tazemetostat, achieved transient responses 15% patients To establish solid mechanistic basis, we investigated role SWI/SNF related BAF chromatin remodeling complex subunit B1 (SMARCB1) via...
The intercalated disc (ID) is a highly specialized cell-cell contact structure that ensures mechanical and electric coupling of contracting cardiomyocytes. Recently, the ID has been recognized to be hot spot cardiac disease, in particular inherited cardiomyopathy.Given its complex function we hypothesized important molecular constituents still remain unknown.Using bioinformatics screen, discovered cloned previously uncharacterized 54 kDa protein which termed Myozap (Myocardium-enriched...
Cholangiocarcinoma (CC) is a rare malignancy of the extrahepatic or intrahepatic biliary tract with an outstanding poor prognosis. Non-surgical therapeutic regimens result in minimally improved survival CC patients. Global genomic analyses identified few recurrently mutated genes, some them genes involved epigenetic patterning. In previous study, we demonstrated global DNA methylation changes CC, indicating major contribution alterations to cholangiocarcinogenesis. Here, aimed at...
Background— We have previously shown that deficiency for the z-disc protein calsarcin-1 (CS1) sensitizes heart to calcineurin signaling and stimuli of pathological hypertrophy. In present study we asked whether overexpression CS1 might exhibit antihypertrophic effects, therefore tested this hypothesis both in vitro vivo. Methods Results— Adenoviral gene transfer into neonatal cardiomyocytes inhibited hypertrophy as a result Gq-agonist stimulation, including angiotensin-II (Ang-II),...
Rationale and Objective: The M-band represents a transverse structure in the center of sarcomeric A-band provides an anchor for myosin-containing thick filaments. In contrast to other structures, eg, Z-disc, only few M-band–specific proteins have been identified date, its exact molecular composition remains unclear. Methods Results: Using bioinformatic approach identify novel heart- muscle-specific genes, we found leucine rich protein, myomasp ( Myo sin-interacting, M -band- ssociated s...
Mutated proteins arising from somatic mutations in tumors are promising targets for cancer immunotherapy. They represent true tumor-specific antigens (TSAs) as they exclusively expressed tumors, reduce the risk of autoimmunity and more likely to overcome tolerance compared wild-type (wt) sequences. Hence, we designed a panel long peptides (LPs, 28–35 aa) comprising driver gene TP35 KRAS frequently found gastrointestinal test their combined immunotherapeutic potential. We increased numbers T...
Primary tumors and distant site metastases form a bidirectionally communicating system. Yet, the molecular mechanisms of this crosstalk are poorly understood. Here, we identified proteolytically cleaved fragments angiopoietin-like 4 (ANGPTL4) as contextually active protumorigenic antitumorigenic contributors in communication ecosystem. Preclinical studies multiple tumor models revealed that C-terminal fragment (cANGPTL4) promoted growth metastasis. In contrast, N-terminal ANGPTL4 (nANGPTL4)...
In order to evaluate the applicability of anthelminthic treatment wild foxes (Vulpes vulpes) limit their infection with Echinococcus multilocularis, bait pellets, each containing 50 mg praziquantel, were repeatedly distributed in an area 566 km2 where many are infected, southern Germany. After six baiting campaigns (15–20 baits/km2) over a period 14 months, prevalence cestode foxes, initially 32%, had fallen 4%. The effect was most pronounced central part treated area, no positive fox found...