A5083433809- Melanoma and MAPK Pathways
- Computational Drug Discovery Methods
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Ferroptosis and cancer prognosis
- RNA regulation and disease
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Prostate Cancer Treatment and Research
- Cancer Immunotherapy and Biomarkers
- RNA Interference and Gene Delivery
- Cutaneous Melanoma Detection and Management
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- melanin and skin pigmentation
- Histone Deacetylase Inhibitors Research
- MicroRNA in disease regulation
- HER2/EGFR in Cancer Research
- SARS-CoV-2 detection and testing
- Cutaneous lymphoproliferative disorders research
- bioluminescence and chemiluminescence research
- AI in cancer detection
- Monoclonal and Polyclonal Antibodies Research
University Hospital of Zurich
2020-2024
University of Zurich
2020-2024
ETH Zurich
2015-2018
Immune checkpoint inhibitors are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events. Proteomic analyses and multiplex cytokine chemokine assays from serum at baseline event onset indicated aberrant T cell activity with differential expression type I III immune signatures. This was in line finding an increase proportion CD4+ cells IL-17A peripheral blood using flow cytometry. Multiplex immunohistochemistry spatial transcriptomics...
Abstract The bioengineering of vascular networks is pivotal to create complex tissues and organs for regenerative medicine applications. However, bioengineered comprising an arterial venous plexus alongside a lymphatic capillary network have not been explored yet. Here, scRNA‐seq first employed investigate the arterio‐venous endothelial cell marker patterning in human fetal juvenile skin. Transcriptomic analysis reveals that markers NRP1 (neuropilin 1) NR2F2 (nuclear receptor subfamily 2...
We present an optimized dissociation protocol for preparing high-quality skin cell suspensions in-depth single-cell RNA-sequencing (scRNA-seq) analysis of fresh and cultured human skin. Our enabled the isolation a consistently high number highly viable cells from small freshly dissociated punch biopsies, which we use scRNA-seq studies. recapitulated not only main populations existing atlases, but also identified rare populations, such as mast cells. Furthermore, effectively isolated single
A biomedical tattoo composed of cells engineered to express a calcium-sensing receptor coupled visible melanin production detects hypercalcemia.
Abstract Clinical management of melanomas with NRAS mutations is challenging. Targeting MAPK signaling only beneficial to a small subset patients due resistance that arises through genetic, transcriptional, and metabolic adaptation. Identification targetable vulnerabilities in NRAS-mutated melanoma could help improve patient treatment. Here, we used multiomics analyses reveal cells adopt mesenchymal phenotype quiescent program resist cellular stress induced by MEK inhibition. The alterations...
Real-time RT-PCR remains a gold standard in the detection of various viral diseases. In coronavirus 2019 pandemic, multiple RT-PCR–based tests were developed to screen for infection. As an emergency response increasing testing demand, we established severe acute respiratory syndrome 2 (SARS-CoV-2) PCR diagnostics platform which compared different commercial and in-house protocols. Four commercial, one customized, protocols evaluated with 92 SARS-CoV-2–positive SARS-CoV-2–negative samples....
The combination of Programmed Cell Death 1 (PD-1) and Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) blockade has dramatically improved the overall survival rate for malignant melanoma. Immune checkpoint blockers (ICBs) limit tumor's immune escape yet only approximately a third all tumors and, in most cases, limited amount time. Several approaches to overcome resistance ICBs are being investigated among which addition epigenetic drugs that expected act on both tumor cells. Guadecitabine,...
Tebentafusp is the first T-cell receptor-based bispecific protein approved for clinical use in HLA-A*02:01+ adult patients with unresectable/metastatic uveal melanoma. It redirects T-cells toward gp100-expressing target cells, frequently inducing skin-related early adverse events. This study investigated immunological and cellular responses using single-cell spatial analysis of skin biopsies from metastatic melanoma treated tebentafusp. 81.8% developed acute cutaneous events, which...
Abstract Multi-omics profiling by CITE-seq bridges the RNA-protein gap in single-cell analysis but has been largely applied to liquid biopsies. Applying clinically relevant solid biopsies characterize healthy tissue and tumor microenvironment is an essential next step translational studies. In this study, gating of cell populations based on their transcriptome signatures for use type-specific ridge plots allowed identification positive antibody signals setting manual thresholds. Next, we...
Basal cell carcinoma (BCC) is the most frequently diagnosed skin cancer and common malignancy in humans. Different morphological subtypes of BCC are associated with a low or high risk recurrence aggressiveness, but underlying biology how individual arise remains largely unknown. As majority BCCs appear to from mutations same pathway, we hypothesized that development, growth invasive potential also influenced by tumour microenvironment and, particular, cancer-associated fibroblasts (CAFs)...
Abstract Biobanking of surplus human healthy and disease-derived tissues is essential for diagnostics translational research. An enormous amount formalin-fixed paraffin-embedded (FFPE), Tissue-Tek OCT embedded or snap-frozen are preserved in many biobanks worldwide have been the basis studies. However, their usage limited to assays that do not require viable cells. The access intact material a prerequisite validation basic research, novel therapeutic target discovery, functional testing....
Abstract Melanoma plasticity and heterogeneity contribute to therapeutic resistance mortality, the ability of melanoma cells switch from melanocytic mesenchymal phenotypes results in increased invasion metastasis. Investigating role these phenotypic states has been challenging due limited marker availability for each cell state. High-parameter molecular methods such as RNAseq have produced more descriptive gene signatures states, but are cell-destructive, labor-intensive, expensive, can take...
Background: Intractable pruritus is a major factor reducing quality of life in patients with cutaneous T-cell lymphoma (CTCL). Traditional antipruritic medication shows little to no efficacy, partly due lack knowledge about the underlying mechanism. We investigate transcriptional signature microenvironment (CME) and particular keratinocytes identify potential targets driving CTCL. Methods: Spatial single-cell transcriptomic profiling was performed on pruritic non-pruritic human CTCL skin...
Abstract Melanomas are the deadliest skin cancers, in part due to cellular plasticity and heterogeneity. Intratumoral heterogeneity drives varied mutable phenotypes, specifically “melanocytic” “mesenchymal” cell states, which result differential functional properties drug responses. Definitive rigorous classification of these phenotypic states has been challenging with conventional biomarker-based methods, high-parameter molecular methods cell-destructive, labor-intensive, time-consuming. To...
Abstract Background : The combination of Programmed Cell Death 1 (PD-1) and Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) blockade has dramatically improved the overall survival rate for malignant melanoma. Immune checkpoint blockers (ICBs) limit tumor’s immune escape yet only approximately a third all tumors and, in most cases, limited amount time. Several approaches to overcome resistance ICBs are being investigated among which addition epigenetic drugs that expected act on both tumor cells....
Abstract Summary Recently, CITE-seq emerged as a multimodal single-cell technology capturing gene expression and surface protein information from the same single cells, which allows unprecedented insights into disease mechanisms heterogeneity, well immune cell profiling. Multiple profiling methods exist, but they are typically focused on either or antibody analysis, not their combination. Moreover, existing software suites easily scalable to multitude of samples. To this end, we designed...
<title>Abstract</title> Immune checkpoint inhibitors (ICIs) are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events (irAEs). Proteomic analysis and multiplex cytokine/chemokine assay from serum at baseline irAEs onset in 82 patients indicated aberrant T-cell activity with differential expression Type I III immune signatures. This was line an increase proportions monocytes decrease IL-17A producing CD4+ T-cells peripheral blood...
Abstract Real-time reverse transcription polymerase chain reaction (RT-PCR) remains a gold standard in detection of various viral diseases. In the COVID-19 pandemic, multiple RT-PCR based tests were developed to screen for infection. As an emergency response growing testing demand, we established SARS-CoV-2 PCR diagnostics platform which compared different commercial and in-house protocols. We evaluated four (CDC 2019-nCoV, Applied Biosystems™ 2019-nCoV Assay Kit v1 TF-SinglePlex, v2...
High cell viability and recovered concentration are typical quality control requirements for single-cell processing data. This protocol describes procedures sampling, live-cell biobanking, preprocessing RNA sequencing, analysis of fine-needle aspiration (FNA) samples the skin. The minimally invasive nature FNA collection is more accepted by patients allows frequent longitudinal resulting in high-quality sequencing data that capture cellular heterogeneity clinical samples.