A5011536112- Inflammatory mediators and NSAID effects
- Estrogen and related hormone effects
- Nanoplatforms for cancer theranostics
- Brain Metastases and Treatment
- RNA modifications and cancer
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- Cancer, Stress, Anesthesia, and Immune Response
- Virus-based gene therapy research
- TGF-β signaling in diseases
- Cancer-related molecular mechanisms research
- NF-κB Signaling Pathways
- Cytokine Signaling Pathways and Interactions
- Cancer Cells and Metastasis
- MicroRNA in disease regulation
- Eicosanoids and Hypertension Pharmacology
- S100 Proteins and Annexins
- interferon and immune responses
- Cancer, Hypoxia, and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Cancer, Lipids, and Metabolism
- Mitochondrial Function and Pathology
- Genetics, Bioinformatics, and Biomedical Research
- Wnt/β-catenin signaling in development and cancer
- PI3K/AKT/mTOR signaling in cancer
German Cancer Research Center
2016-2025
Heidelberg University
2016-2025
DKFZ-ZMBH Alliance
2006-2023
Weizmann Institute of Science
2022
University Hospital Heidelberg
2017
Goethe University Frankfurt
2011
Friedrich Schiller University Jena
2006
Charité - Universitätsmedizin Berlin
2005
German Institute for Cell and Tissue Replacement
1998
Cancer Research Center
1995
Obesity results from chronic energy surplus and excess lipid storage in white adipose tissue (WAT). In contrast, brown (BAT) efficiently burns lipids through adaptive thermogenesis. Studying mouse models, we show that cyclooxygenase (COX)-2, a rate-limiting enzyme prostaglandin (PG) synthesis, is downstream effector of beta-adrenergic signaling WAT required for the induction BAT depots. PG shifted differentiation defined mesenchymal progenitors toward adipocyte phenotype. Overexpression...
A broad range of experimental and clinical evidence has highlighted the central role chronic inflammation in promoting tumor development. However, molecular mechanisms converting a transient inflammatory tissue reaction into tumor-promoting microenvironment remain largely elusive. We show that mice deficient for receptor advanced glycation end-products (RAGE) are resistant to DMBA/TPA-induced skin carcinogenesis exhibit severe defect sustaining during promotion phase. Accordingly, RAGE is...
Abstract In colorectal cancer (CRC), aberrant Wnt signalling is essential for tumorigenesis and maintenance of stem cells. However, how other oncogenic pathways converge on to modulate cell homeostasis in CRC currently remains poorly understood. Using large-scale compound screens CRC, we identify MEK1/2 inhibitors as potent activators Wnt/β-catenin signalling. Targeting MEK increases activity different lines murine intestine vivo. Truncating mutations APC generated by CRISPR/Cas9 strongly...
Abstract Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is known to contain an active-site cysteine residue undergoing oxidation in response hydrogen peroxide, leading rapid inactivation of the enzyme. Here we show that human and mouse cells expressing a GAPDH mutant lacking this redox switch retain catalytic activity but are unable stimulate oxidative pentose phosphate pathway enhance their reductive capacity. Specifically, find anchorage-independent growth spheroids limited by elevation...
Genetic and pharmacological evidence suggests that overexpression of cyclooxygenase-2 (COX-2) is critical for epithelial carcinogenesis provides a major target cancer chemoprevention by nonsteroidal antiinflammatory drugs. Transgenic mouse lines with keratin 5 promoter-driven COX-2 in basal epidermal cells exhibit preneoplastic skin phenotype. As shown here, this phenotype depends on the level expression COX-2-mediated prostaglandin accumulation. The transgenics did not develop tumors...
In prostanoid biosynthesis, the first two steps are catalyzed by cyclooxygenases (COX). mice and humans, deregulated expression of COX-2, but not COX-1, is characteristic epithelial tumors, including squamous cell carcinomas skin. To explore function COX-2 in epidermis, a keratin 5 promoter was used to direct basal cells interfollicular epidermis pilosebaceous appendage transgenic mouse overexpression expected locations, resulting increased prostaglandin levels plasma, correlated with...
Abstract Introduction Breast cancer stem cells are suspected to be responsible for tumour recurrence, metastasis formation as well chemoresistance. Consequently, great efforts have been made understand the molecular mechanisms underlying cell maintenance. In order study these rare in-vitro , they typically enriched via mammosphere culture. Here we developed a mammosphere-based negative selection shRNAi screening system suitable analyse involvement of thousands genes in survival with...
Abstract Pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions, pancreatic intraepithelial neoplasia (PanIN), display a phenotype. However, there is evidence in genetically defined mouse models for PDAC harbouring mutated kras under the control of pancreas‐specific promoter that cancer might arise centroacinar‐acinar region, possibly through process acinar‐ductal metaplasia (ADM). In order to further elucidate this model development, an extensive expression analysis molecular...
Cutaneous beta human papillomavirus (HPV) types are suspected to be involved, together with ultraviolet (UV) radiation, in the development of non-melanoma skin cancer (NMSC). Studies vitro and vivo experimental models have highlighted transforming properties HPV E6 E7 oncoproteins. However, epidemiological findings indicate that may required only at an initial stage carcinogenesis, become dispensable after full establishment NMSC. Here, we further investigate potential role HPVs NMSC using a...
Malignant melanoma is the deadliest of skin cancers. Melanoma frequently metastasizes to brain, resulting in dismal survival. Nevertheless, mechanisms that govern early metastatic growth and interactions disseminated cells with brain microenvironment are largely unknown. To study hallmarks niche formation, we established a transplantable model spontaneous metastasis immunocompetent mice developed molecular tools for quantitative detection micrometastases. Here demonstrate micrometastases...
Mammalian cells can generate amino acids through macropinocytosis and lysosomal breakdown of extracellular proteins, which is exploited by cancer to grow in nutrient-poor tumors. Through genetic screens defined nutrient conditions, we characterized LYSET, a transmembrane protein (TMEM251) selectively required when consume proteins. LYSET was found associate the Golgi with GlcNAc-1-phosphotransferase, targets catabolic enzymes lysosomes mannose-6-phosphate modification. Without...
An anti-tumor-promoting effect of indomethacin and related nonsteroidal anti-inflammatory drugs (NSAIDs) as well the ability tumor promoter 12-O-tetradecanoylphorbol-13- acetate (TPA) to increase level prostaglandins in murine keratinocytes mouse epidermis vivo has been repeatedly documented. Here, expression prostaglandin H synthase (PGHS) isozymes, which are major targets NSAIDs, was investigated different stages development skin. Mouse constitutively expressed PGHS-1. PGHS-1 steady-state...
Non-small cell lung cancer (NSCLC) is characterized by early metastasis and has the highest mortality rate among all solid tumors, with majority of patients diagnosed at an advanced stage where curative therapeutic options are lacking. In this study, we identify a targetable mechanism involving TGFβ elevation that orchestrates tumor progression in disease. Substantial activation pathway was detected human tissues concomitant downregulation BAMBI, negative regulator signaling pathway....
A cryogenic chemical processing method maps the redox state at cellular and subcellular level in tissue sections.
Human induced pluripotent stem cells (hiPSC) harbor the potential to differentiate into diverse cardiac cell types. Previous experimental efforts were primarily directed at generation of hiPSC-derived with ventricular cardiomyocyte characteristics. Aiming a straightforward approach for pacemaker modeling and replacement, we sought selectively nodal-type properties. hiPSC differentiated spontaneously beating clusters by co-culturing visceral endoderm-like in serum-free medium. Subsequent...
The growth factor- and phorbol ester-inducible prostaglandin H synthase (PGHS)-2 has been found to be constitutively overexpressed in epidermal tumors generated by the initiation-promotion protocol murine skin, whereas expression of PGHS-1 does not change under these conditions. In this paper we report intra-tumor distribution aberrantly expressed PGHS-2 cancer chemopreventive activity a specific inhibitor. By immunohistochemical methods using isoenzyme-specific antibodies, that protein was...