A5033176466- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cancer-related Molecular Pathways
- Cancer Cells and Metastasis
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Pancreatic and Hepatic Oncology Research
- Cancer Research and Treatments
- Acute Myeloid Leukemia Research
- NF-κB Signaling Pathways
- Protein Degradation and Inhibitors
- Cancer Mechanisms and Therapy
- Multiple Myeloma Research and Treatments
- Cytokine Signaling Pathways and Interactions
- Mechanisms of cancer metastasis
- Protein Tyrosine Phosphatases
- Peptidase Inhibition and Analysis
- Galectins and Cancer Biology
- Microtubule and mitosis dynamics
- Chemokine receptors and signaling
Technical University of Munich
2023-2024
University Hospital of Basel
2021-2023
University of Basel
2021-2023
Klinikum rechts der Isar
2023
Abstract Tumor-specific T cells are frequently exhausted by chronic antigenic stimulation. We here report on a human antigen-specific ex vivo model to explore new therapeutic options for cell immunotherapies. generated with this resemble tumor-infiltrating phenotypic and transcriptional level. Using targeted pooled CRISPR-Cas9 screen individual gene knockout validation experiments, we uncover sorting nexin-9 (SNX9) as mediator of exhaustion. Upon TCR/CD28 stimulation, deletion SNX9 in CD8...
A genome-wide PiggyBac transposon-mediated screen and a resistance in PIK3CAH1047R-mutated murine tumor model reveal NF1 loss mammary tumors resistant to the phosphatidylinositol 3-kinase α (PI3Kα)-selective inhibitor alpelisib. Depletion of PIK3CAH1047R breast cancer cell lines patient-derived organoid shows that reduces sensitivity PI3Kα inhibition correlates with enhanced glycolysis lower levels reactive oxygen species (ROS). Unexpectedly, antioxidant N-acetylcysteine (NAC) sensitizes...
Abstract Plasticity delineates cancer subtypes with more or less favourable outcomes. In breast cancer, the subtype triple-negative lacks expression of major differentiation markers, e.g., estrogen receptor α (ERα), and its high cellular plasticity results in greater aggressiveness poorer prognosis than other subtypes. Whether itself represents a potential vulnerability cells is not clear. However, we show here that cell can be exploited to differentiate (TNBC). Using high-throughput...
Treatment of metastasis remains a clinical challenge and the majority breast cancer-related deaths are result drug-resistant metastases. The protein tyrosine phosphatase SHP2 encoded by proto-oncogene PTPN11 promotes cancer progression. Inhibition has been shown to decrease metastases formation in various models, but specific downstream effectors remain poorly characterized. Certain cytokines metastatic cascade facilitate local invasion promote colonization. In this study, we investigated...
Abstract T-cell exhaustion poses a significant barrier to the efficacy of immunotherapies. In past decade, immune checkpoint blockade (ICB) has been leading strategy prevent or reverse exhaustion. Although ICB yields promising clinical outcomes in patients with cancer, its impact on reinvigoration is often short-lived. High-throughput genomic tools, including CRISPR screening along single-cell RNA and chromatin accessibility sequencing may point toward new therapeutic avenues. However, their...