A5016968396- Cellular Mechanics and Interactions
- Textile materials and evaluations
- Single-cell and spatial transcriptomics
- Wound Healing and Treatments
- Nonmelanoma Skin Cancer Studies
- Cancer and Skin Lesions
- Elasticity and Material Modeling
- Hedgehog Signaling Pathway Studies
- Lymphatic System and Diseases
- T-cell and B-cell Immunology
- Cell Adhesion Molecules Research
- Melanoma and MAPK Pathways
- 3D Printing in Biomedical Research
- Silk-based biomaterials and applications
- Immunotherapy and Immune Responses
- Psoriasis: Treatment and Pathogenesis
- Tumors and Oncological Cases
- Diagnosis and Treatment of Venous Diseases
- Histone Deacetylase Inhibitors Research
- Skin Protection and Aging
- Wnt/β-catenin signaling in development and cancer
- Urticaria and Related Conditions
- Craniofacial Disorders and Treatments
- Genetic and rare skin diseases.
- Heat shock proteins research
University Hospital of Zurich
2018-2025
University of Zurich
2017-2024
University of Lausanne
2010-2011
Abstract Toxic epidermal necrolysis (TEN) is a fatal drug-induced skin reaction triggered by common medications and an emerging public health issue 1–3 . Patients with TEN undergo severe sudden detachment caused keratinocyte cell death. Although molecular mechanisms that drive death have been proposed, the main drivers remain unknown, there no effective therapy for 4–6 Here, to systematically map changes are associated identify potential druggable targets, we utilized deep visual proteomics,...
Cleft palate is a common congenital disorder that affects up to 1 in 2,500 live human births and results considerable morbidity affected individuals their families. The etiology of cleft complex, with both genetic environmental factors implicated. Mutations the transcription factor-encoding genes p63 interferon regulatory factor 6 (IRF6) have individually been identified as causes palate; however, relationship between key IRF6 has not determined. Here, we used mouse models primary...
The mechanical properties of the skin determine tissue function and regulate dermal cell behavior. Yet measuring these remains challenging, as evidenced by large range elastic moduli reported in literature-from below one kPa to hundreds MPa. Here, we reconcile disparate results dedicated experiments at both cellular length scales computational models considering multiscale multiphasic structure. At macroscopic scale, collective behavior collagen fiber network under tension provides...
Abstract Cutaneous melanoma represents the most fatal skin cancer due to its high metastatic capacity. According “phenotype switching” model, aggressive nature of cells results from their intrinsic potential dynamically switch a high-proliferative/low-invasive low-proliferative/high-invasive state. Here we identify low affinity neurotrophin receptor CD271 as key effector phenotype switching in melanoma. plays dual role this process by decreasing proliferation, while simultaneously promoting...
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
Chronic wounds represent a major therapeutic challenge. Lymphatic vessel function is impaired in chronic ulcers but the role of lymphangiogenesis wound healing has remained unclear. We found that lymphatic vessels are largely absent from human as evaluated patient biopsies. Excisional studies were conducted using transgenic mice with or without an increased number cutaneous vessels, well antibody-mediated inhibition lymphangiogenesis. lack mediated proinflammatory microenvironment and...
Abstract The present study investigates the multiphasic nature of mechanical behavior human dermis. Motivated by experimental observations and consideration its composition, a quadriphasic model dermis is proposed, distinguishing solid matrix components, interstitial fluid charged constituents moving within fluid, i.e., anions cations. Compression tensile experiments with without change osmolarity bath are performed to characterize chemo-mechanical coupling in Model parameters determined...
The present study investigates the layer-specific mechanical behavior of human skin. Motivated by skin's histology, a biphasic model is proposed which differentiates between epidermis, papillary and reticular dermis, hypodermis. Inverse analysis ex vivo tensile in suction experiments yields parameters for each layer predicts stiff dermis successively softer epidermis Layer-specific simulations underlines dominating role loading. Furthermore, it shows that observed out-of-plane deflection...
Exudates of nonhealing wounds contain drivers pathogenicity. We utilized >800 exudates from and healing diverse etiologies, collected by 3 different methods, to develop a wound-specific, cell-based functional biomarker assay. Human dermal fibroblast proliferation served as readout (i) differentiate between wounds, (ii) follow the process individual patients, (iii) assess effects therapeutics for chronic ex vivo. observed strong correlation wound chronicity inhibitory on proliferation, with...
Summary Loss of keratinocyte differentiation is a leading cause in several skin diseases and needs to be controlled adult homeostasis by for instance growth factors proteases. Among them, we studied the role isoform-rich dermokine – wound- tumour-related matrix metalloproteinase 10 substrate via functional multi-omics. We generated isoform-dependent knockouts three dimensional (3D) organotypic cultures analyzed changes their proteome phosphoproteome quantitative mass spectrometry. Through...
Ample evidence pinpoints the phenotypic diversity of blood vessels (BVs) and site-specific functions their lining endothelial cells (ECs). We harnessed single-cell RNA sequencing (scRNA-seq) to dissect molecular heterogeneity vascular (BECs) in healthy adult human skin identified six different subpopulations, signifying arterioles, post-arterial capillaries, pre-venular post-capillary venules, venules collecting venules. Individual BEC subtypes exhibited distinctive transcriptomic landscapes...
Human papillomavirus (HPV)-driven cutaneous squamous cell carcinoma (cSCC) is the most common cancer in immunosuppressed patients. Despite indications suggesting that HPV promotes genomic instability during cSCC development, molecular pathways underpinning HPV-driven development remain unknown. We compared transcriptome of mouse with normal skin and observed higher amounts transcripts for Porcupine WNT ligands cSCC, a role signaling progression. confirmed increased expression human samples....
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)...
Psoriasis is a chronic inflammatory skin disease that often recurs at the same locations, indicating potential epigenetic changes in lesional cells. In this study, we discovered fibroblasts isolated from psoriatic lesions retain an abnormal phenotype even after several passages culture. Transcriptomic profiling revealed upregulation of genes, including extra domain A splice variant fibronectin and ITGA4 fibroblasts. phenotypic library screening small-molecule modifier drugs selective...
Epithelial skin cancers are extremely common, but the mechanisms underlying their malignant progression still poorly defined. Here, we identify NRF3 transcription factor as a tumor suppressor in skin. protein expression is strongly downregulated or even absent invasively growing cancer cells of patients with basal and squamous cell carcinomas (BCC SCC). deficiency promoted conversion chemically induced tumors immunocompetent mice, clonogenic growth migration human SCC cells, invasiveness 3D...
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....
Dendritic cell (DC) migration from peripheral tissues via afferent lymphatic vessels to draining lymph nodes (dLNs) is important for the organism’s immune regulation and protection. Several endothelial (LEC)-expressed adhesion molecules have thus far been found support transmigration movement within vasculature. In this study, we investigated contribution of CD112, an molecule that recently be highly expressed in murine LECs, process. Performing vitro assays system, bone marrow-derived...
Human skin equivalents (HSEs) serve as important tools for mechanistic studies with human cells, drug discovery, pre-clinical applications in the field of tissue engineering and transplantation on defects. Besides cellular extracellular matrix (ECM) components used HSEs, physical constraints applied scaffold during HSEs maturation influence organization, functionality, homogeneity. In this study, we introduce a 3D-printed culture insert that exposes bi-layered to static radial constraint...