A5044489751- Hair Growth and Disorders
- Cancer Cells and Metastasis
- Skin and Cellular Biology Research
- Nonmelanoma Skin Cancer Studies
- Wound Healing and Treatments
- Immunotherapy and Immune Responses
- Wnt/β-catenin signaling in development and cancer
- Hedgehog Signaling Pathway Studies
- Cutaneous Melanoma Detection and Management
- Cancer Immunotherapy and Biomarkers
- Cell Image Analysis Techniques
- Hippo pathway signaling and YAP/TAZ
- Immune cells in cancer
- Melanoma and MAPK Pathways
- Cutaneous lymphoproliferative disorders research
- HER2/EGFR in Cancer Research
- Chemokine receptors and signaling
- Single-cell and spatial transcriptomics
- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- melanin and skin pigmentation
- Skin Protection and Aging
- Cancer and Skin Lesions
- Immune Cell Function and Interaction
- Nail Diseases and Treatments
Medical University of Vienna
2013-2024
Comprehensive Cancer Center Vienna
2013-2019
King's College London
2014-2019
GP Forschungsgruppe
2019
Pädagogische Hochschule Salzburg
2019
Paracelsus Medical University
2019
Paracelsus Medizinische Privatuniversität
2019
Christ University
2019
University Dermatology
2019
Guy's Hospital
2016-2017
The epidermal growth factor receptor (EGFR) plays an important role in tissue homeostasis and tumor progression. However, cancer patients treated with EGFR inhibitors (EGFRIs) frequently develop acneiform skin toxicities, which are a strong predictor of patient's treatment response. We show that the early inflammatory infiltrate rash induced by EGFRI is dominated dendritic cells, macrophages, granulocytes, mast T cells. EGFRIs induce expression chemokines (CCL2, CCL5, CCL27, CXCL14)...
Significance The synchronized patterns of hair follicle growth and expansion the dermal adipocyte layer have long been recognized. Although factors secreted by adipocytes are known to regulate cycle, it is unclear whether, conversely, epidermis can adipogenesis. Our study now demonstrates that activation epidermal Wnt/β-catenin signaling stimulates differentiation in vivo vitro. effect be mediated factors, including insulin-like factor 2 bone morphogenetic proteins 6.
Human skin dermis is composed of the superficial papillary and reticular in lower layers, which can easily be distinguished histologically. In vitro analyses fibroblasts from explant cultures dermal layers suggest that human comprises at least two fibroblast lineages with distinct morphology, expression profiles, functions. However, while for mouse cell surface markers have been identified, allowing isolation pure populations one lineage or other via FACS, this has not achieved fibroblasts....
Though skin fibroblasts (FB) are the main cell population within dermis, different FB subsets not well characterized and traditional classification into reticular papillary FBs has little functional relevance. To fill gap of knowledge on diversity in human skin, we performed single-cell RNA sequencing. Investigation marker genes for subtypes revealed a heterogeneous picture FBs. When mapping markers, could detect cluster specificity, suggesting that these two populations show higher...
Abstract Sustained epidermal Wnt/β-catenin signalling expands the stem cell compartment and induces ectopic hair follicles (EFs). This is accompanied by extensive fibroblast proliferation extracellular matrix (ECM) remodelling in underlying dermis. Here we show that Hedgehog (Hh) Transforming growth factor-beta (TGF-β) mediate dermal changes. Pharmacological inhibition or genetic deletion of these pathways prevents β-catenin-induced reprogramming EF formation. Epidermal Shh stimulates...
The Wnt/β-catenin pathway plays a central role in epidermal homeostasis and regeneration, but how it affects fibroblast fate decisions is unknown. We investigated the effect of targeted β-catenin stabilization dermal fibroblasts. Comparative gene expression profiling stem cell antigen 1- (Sca1-) Sca1+ neonatal fibroblasts from upper lower dermis, respectively, confirmed that cells had preadipocyte signature showed differential Wnt/β-catenin–associated genes. By targeting all or selectively...
A wealth of specialized cell populations within the skin facilitates its hair-producing, protective, sensory, and thermoregulatory functions. How vast cell-type diversity tissue architecture develops is largely unexplored. Here, with single-cell transcriptomics, spatial assignment, cell-lineage tracing, we deconstruct early embryonic mouse during key transitions from seemingly uniform developmental precursor states to a multilayered, multilineage epithelium, complex dermal identity. We...
Cancer-associated fibroblasts (CAFs) play a key role in cancer progression and treatment outcome. This study dissects the intra-tumoral diversity of CAFs basal cell carcinoma, squamous melanoma using molecular spatial single-cell analysis. We identify three distinct CAF subtypes: myofibroblast-like RGS5+ CAFs, matrix (mCAFs), immunomodulatory (iCAFs). Large-cohort tissue analysis reveals significant shifts subtype patterns with increasing malignancy. Two subtypes exhibit properties via...
Abstract Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal neoplastic (cutaneous squamous cell carcinoma, cSCC) cells. The Hippo effector YAP was amongst top positive regulators both screens. By integrating network interactome with our data sets, identify WW-binding protein 2 (WBP2) as an...
B-lymphocyte-induced maturation protein 1 (Blimp1) is a transcriptional repressor that regulates cell growth and differentiation in multiple tissues, including skin. Although the epidermis Blimp1 important for keratinocyte sebocyte differentiation, its role dermal fibroblasts unclear. Here we show dynamically regulated papilla cells during hair follicle (HF) morphogenesis postnatal cycle, preceding Wnt/β-catenin activation. ablation E12.5 mouse delayed HF prevented new formation after...
Epidermal growth factor receptor (EGFR)-targeted anticancer therapy induces stigmatizing skin toxicities affecting patients' quality of life and adherence. The lack mechanistic details underlying these adverse events hampers their management. We found that EGFR/ERK signaling is required in LRIG1-positive stem cells during de novo hair eruption to secure barrier integrity prevent the invasion commensal microbiota inflammatory disease. EGFR-deficient epidermis permissive for outgrowth displays...
Prominin-1/CD133 (Prom1) is expressed by fibroblasts in the dermal papilla (DP) of hair follicle (HF). By examining endogenous Prom1 expression and LacZ skin Prom1CreERLacZ (Prom1C–L) mice, which a CreERT2-IRES-nuclear cassette knocked into first ATG codon Prom1, we confirmed that DP all developing HFs also postnatal anagen follicles. To analyze fate Prom1+ cells, crossed Prom1C–L mice with Rosa26-CAG flox/stop/flox tdTomato reporter applied 4-hydroxytamoxifen (4OHT) to back at day (P) 1 P2....
Melanoma cells can switch between distinct gene expression profiles, resulting in proliferative or invasive phenotypes. Signaling pathways involved this were analyzed by profiling of a cohort 22 patient-derived melanoma cell lines. CDH1 negativity was identified as surrogate marker for the phenotype. could be turned on and off modulating activity p38 its downstream target MK2, suggesting that pathway controls progression. Mechanistically, MK2 inhibition prevented melanoma-induced vascular...
Epidermal growth factor receptor (EGFR) signaling controls skin development and homeostasis in mice humans, its deficiency causes severe inflammation, which might affect epidermal stem cell behavior. Here, we describe the inflammation-independent effects of EGFR during morphogenesis adult hair follicle cells. Expression alternative splicing analysis RNA sequencing data from interfollicular epidermis outer root sheath indicate that genes involved differentiation also centrosome function, DNA...
Epidemiological and experimental data implicate cutaneous human papillomavirus infection as co-factor in the development of squamous cell carcinomas (cSCCs), particularly immunocompromised organ transplant recipients (OTRs). Herein, we established characterized a skin cancer model, which Mus musculus 1 (MmuPV1) caused cSCCs cyclosporine A (CsA)-treated mice, even absence UV light. Development their precursors were observed 70% MmuPV1-infected, CsA-treated mice on back well tail skin....
Fibroblasts are a highly heterogeneous cell population implicated in the pathogenesis of many human diseases. In skin dermis, fibroblasts have traditionally been attributed to superficial papillary or lower reticular dermis according their histological localization. mouse and originate from two different lineages with diverging functions regarding physiological pathological processes distinct surface marker expression profile by which they can be distinguished. Importantly, evidence explant...