A5047903078- Renal cell carcinoma treatment
- Renal and related cancers
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Genetic and Kidney Cyst Diseases
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
- DNA Repair Mechanisms
- Pancreatic and Hepatic Oncology Research
- Environmental Toxicology and Ecotoxicology
- Pesticide Exposure and Toxicity
- Cancer-related Molecular Pathways
- Genetic factors in colorectal cancer
- Parathyroid Disorders and Treatments
- Genomics and Rare Diseases
- Bioinformatics and Genomic Networks
- Tuberous Sclerosis Complex Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer, Hypoxia, and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Parasite Biology and Host Interactions
- Bacterial Genetics and Biotechnology
- interferon and immune responses
Essen University Hospital
2018-2024
German Cancer Research Center
2016-2023
Heidelberg University
2016-2023
Deutschen Konsortium für Translationale Krebsforschung
2019-2023
German Cancer Society
2023
The University of Texas Southwestern Medical Center
2011-2019
National Center for Tumor Diseases
2016-2019
University Hospital Heidelberg
2018
Southwestern Medical Center
2011-2016
Harvard University
2005-2014
The master regulator of lysosome biogenesis, TFEB, is regulated by MTORC1 through phosphorylation at S211, and a S211A mutation increases nuclear localization. However, TFEBS211A localizes diffusely in both cytoplasm nucleus and, as we show, retains regulation MTORC1. Here, report that endogenous TFEB phosphorylated S122 an MTORC1-dependent manner, vitro recombinant MTOR, important for Specifically, localization following inhibition blocked S122D (despite S211 dephosphorylation)....
Most anticancer drugs entering clinical trials fail to achieve approval from the U.S. Food and Drug Administration. development is hampered by lack of preclinical models with therapeutic predictive value. Herein, we report validation a tumorgraft model renal cell carcinoma (RCC) its application evaluation an experimental drug. Tumor samples 94 patients were implanted in kidneys mice without additives or disaggregation. Tumors 35 these formed tumorgrafts, 16 stable lines established. Samples...
Abstract Renal cell carcinoma (RCC) clusters in some families. Familial RCC arises from mutations several genes, including the von Hippel-Lindau (VHL) tumor suppressor, which is also mutated sporadic RCC. However, a significant percentage of familial remains unexplained. Recently, we discovered that BRCA1-associated protein-1 (BAP1) gene The BAP1 encodes nuclear deubiquitinase and appears to be classic two-hit suppressor gene. Somatic are associated with high-grade, clear-cell (ccRCC) poor...
mTOR complex 1 (mTORC1) is implicated in cell growth control and extensively regulated. We previously reported that response to hypoxia, mTORC1 inhibited by the protein regulated development DNA damage (REDD1). REDD1 upregulated hypoxia-inducible factor (HIF)-1, forced expression sufficient inhibit mTORC1. REDD1-induced inhibition dependent on a formed tuberous sclerosis (TSC)1 2 (TSC2) proteins. In clear-cell renal carcinoma (ccRCC), von Hippel-Lindau (VHL) gene frequently inactivated...
We have uncovered a role for Jumonji inhibitors in overcoming radioresistance through KDM5B inhibition. Pharmacological blockade of demethylases with JIB-04 leads to specific accumulation H3K4me3 at sites marked by γH2AX and impaired recruitment DNA repair factors, preventing resolution damage resulting robust sensitization radiation therapy. In DNA-repair-proficient cancer cells, knockdown the demethylase KDM5B, but not other enzymes, mimics pharmacological inhibition, overexpression...
The soxRS regulon of Escherichia coli and Salmonella enterica is induced by redox-cycling compounds or nitric oxide provides resistance to superoxide-generating agents, macrophage-generated oxide, antibiotics, organic solvents. We have previously shown that constitutive expression can contribute quinolone in clinically relevant S. enterica. In this work, we carried out an analysis the mechanism soxS its role antibiotic E. clinical isolates. show three six strains was caused single point...
Tumor-associated macrophage (TAM) significantly contributes to cancer progression. Human is enhanced by PPARγ loss-of-function mutations, but inhibited agonists such as TZD diabetes drugs including rosiglitazone. However, it remains enigmatic whether and how tumor-suppressive functions. Here we report that deletion in mice not only exacerbates mammary tumor development also impairs the anti-tumor effects of Mechanistically, identify Gpr132 a novel direct target whose expression loss...
Abstract GRB2 is an adaptor protein of HER2 (and several other tyrosine kinases), which we identified as a novel BECN1 (Beclin 1) interacting partner. co-immunoprecipitated with in breast cancer cell lines and regulates autophagy through mechanism involving the modulation class III PI3Kinase VPS34 activity. In ovo studies CAM (Chicken Chorioallantoic Membrane) model indicated that knockdown, well overexpression loss-of-function mutants (Y52A S86A-R88A) compromised tumor growth. These...
To assess pathological correlations and temporal trends of Angiopoietin-2 (ANGPT2), vascular endothelial growth factor (VEGF) M2 Pyruvate kinase (TuM2PK), markers tumor development metabolism, in patients with renal cell carcinoma (RCC). We prospectively collected plasma samples from 89 who underwent surgical/ablative therapy for RCC 38 benign disease (nephrolithiasis, hematuria without apparent neoplastic origin, or cysts). In patients, marker levels were compared between at least 1...
Abstract Oncogenic KRAS mutations are encountered in more than 90% of pancreatic ductal adenocarcinomas. MEK inhibition has failed to procure any clinical benefits mutant RAS-driven cancers including adenocarcinoma (PDAC). To identify potential resistance mechanisms underlying inhibitor (MEKi) PDAC, we investigated lysosomal drug accumulation PDAC models both vitro and vivo. Mouse human cell lines as well xenografts treated with the trametinib or refametinib led an enhanced expression...
Abstract Background The cellular tumor protein p53 ( TP53 ) is a suppressor gene that frequently mutated in human cancers. Among various cancer types, the very aggressive high‐grade serous ovarian carcinoma (HGSOC) exhibits highest prevalence of mutations, present >96% cases. Despite intensive efforts to reactivate p53, no clinical drug has been approved rescue function. In this study, our primary objective was administer vitro‐transcribed (IVT) wild‐type (WT) p53‐mRNA HGSOC cell lines,...