A5064788187- Skin and Cellular Biology Research
- Wnt/β-catenin signaling in development and cancer
- Autoimmune Bullous Skin Diseases
- Hair Growth and Disorders
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer-related Molecular Pathways
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Hedgehog Signaling Pathway Studies
- Congenital Diaphragmatic Hernia Studies
- RNA modifications and cancer
- Neonatal Respiratory Health Research
- Polyamine Metabolism and Applications
- CRISPR and Genetic Engineering
- Cell Adhesion Molecules Research
- HIV Research and Treatment
- Biotin and Related Studies
- Plant Reproductive Biology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Fibroblast Growth Factor Research
- Nuclear Structure and Function
- Kruppel-like factors research
- Dermatologic Treatments and Research
East Carolina University
2021-2023
Gates (United States)
2008-2019
University of Colorado Denver
2008-2019
Technische Hochschule Mittelhessen
2019
University of Colorado Anschutz Medical Campus
2011-2018
Universitätsklinikum Erlangen
2016
Heidelberg University
1990-2014
University Hospital Heidelberg
2009-2014
University of Freiburg
2014
In-Q-Tel
2014
Patients with pemphigus foliaceus (PF) have blisters on skin, but not mucous membranes, whereas patients vulgaris (PV) develop membranes and/or skin. PF and PV are due to loss of keratinocyte cell–cell adhesion in the superficial deep epidermis, respectively. autoantibodies directed against desmoglein (Dsg) 1; bind Dsg3 or both Dsg1. In this study, we test hypothesis that coexpression Dsg1 keratinocytes protects pathology antibody-induced dysfunction either one alone. Using passive transfer...
In patients with pemphigus vulgaris (PV), autoantibodies against desmoglein 3 (Dsg3) cause loss of cell–cell adhesion keratinocytes in the basal and immediate suprabasal layers stratified squamous epithelia. The pathology, at least partially, may depend on protease release from keratinocytes, but might also result antibodies interfering an function Dsg3. However, a direct role desmogleins cell has not been shown. To test whether Dsg3 mediates adhesion, we genetically engineered mice targeted...
The epidermal cornified cell envelope (CE) is a complex protein–lipid composite that replaces the plasma membrane of terminally differentiated keratinocytes. This lamellar structure essential for barrier function skin and has ability to prevent loss water ions protect from environmental hazards. major protein CE loricrin, contributing ∼70% by mass. We have generated mice are deficient this protein. These showed delay in formation embryonic development. At birth, homozygous mutant weighed...
In Patients with pemphigus vulgaris, autoantibodies against the desmosomal glycoprotein desmoglein 3 (Dsg3) cause blisters due to loss of keratinocyte cell-cell adhesion in basal and immediate suprabasal layer deeper epidermis, leaving superficial epidermis intact. Autoantibodies from these patients, however, usually bind cell surface keratinocytes throughout entire as determined by indirect immunofluorescence. To explain this apparent paradox, we immunoadsorbed vulgaris sera extracellular...
Desmosomes are intercellular junctions that contain two major kinds of transmembrane glycoproteins, desmoglein and desmocollins I II, involved in cell-cell adhesion. Recent sequence analyses have shown both desmosomal glycoproteins belong to the larger cadherin family cell adhesion molecules, which they represent different subgroups characterized by their specific topogenesis. In cDNA sequences Northern blot experiments we now found not unique gene products but occur subtypes produced from...
Little is known about the function of desmosomes in normal structure and hair. Therefore, it was surprising that mice without desmoglein 3 (the autoantigen pemphigus vulgaris) not only developed mucous membrane skin lesions like patients, but also hair loss. Analysis this phenotype indicated through first growth phase ('follicular neogenesis'). Around day 20, however, when follicles entered resting cycle (telogen), with a targeted disruption gene (DSG3-/-) lost wave-like pattern from head to...
Desmocollin 3 (DSC3) belongs to a subfamily of cadherins and is major component desmosomes in keratinocytes stratified epithelia, such as the epidermis. Based on its amino acid sequence homology classical cadherins, E-cadherin, it has been postulated that DSC3 functions cell-adhesion molecule. To test this hypothesis, we assessed function development maintenance particular epidermis hair follicles. Using conditional null allele, show loss Dsc3 causes impaired cell–cell adhesion, leading...
Deformed wing virus (DWV) is an emerging infectious disease of the honey bee (Apis mellifera) that considered a major cause elevated losses colonies. DWV comprises two widespread genotypes: originally described genotype A, and B. In adult bees, DWV-B has been shown to be more virulent than DWV-A. However, their comparative effects on earlier host developmental stages are unknown. Here, we experimentally inoculated pupae tested for relative impact DWV-A versus mortality deformities in...
Bullous pemphigoid antigen 180 (BP180) is a component of hemidesmosomes, i.e., cell-substrate adhesion complexes. To determine the function specific sequences BP180 to its incorporation in we have transfected 804G cells with cDNA-constructs encoding wild-type and deletion mutant forms human BP180. The results show that cytoplasmic domain contains sufficient information for recruitment protein into hemidesmosomes because removal extracellular transmembrane domains does not abolish targeting....
Netherton syndrome (NS) is a human autosomal recessive skin disease caused by mutations in the SPINK5 gene, which encodes putative proteinase inhibitor LEKTI. We have generated transgenic mouse line with an insertional mutation that inactivated ortholog. Mutant mice exhibit fragile stratum corneum and perinatal death due to dehydration. Our analysis suggests phenotype consequence of desmosomal fragility associated premature proteolysis corneodesmosin, extracellular component. mutant provides...
Mesenchymal stem cells (MSCs) exhibit broad immune modulatory activity in vivo and can suppress T cell proliferation dendritic activation vitro. Currently, most MSC for clinical usage are derived from younger donors, due to ease of procurement the superior activity. However, use multiple unrelated donors makes it difficult standardize study results compare outcomes between different trials. One solution is induced pluripotent (iPSC); as iPSC-derived have nearly unlimited proliferative...
Desmocollin 3 (Dsc3) is a transmembrane glycoprotein that belongs to the cadherin family of cell adhesion receptors. Together with desmoglein(s), it forms core desmosomes, multiprotein complex involved in adhesion, organization cytoskeleton, sorting and signaling. Previous reports have suggested Dsc3 synthesis largely restricted stratified epithelia, plays role proper differentiation these tissues during mammalian embryonic development. To test hypotheses, we generated Dsc3-null mice....
Evidence has accumulated that changes in intracellular signaling downstream of desmoglein 3 (Dsg3) may have a significant role epithelial blistering the autoimmune disease pemphigus vulgaris (PV). Currently, most studies on PV involve passive transfer pathogenic antibodies into neonatal mice not finalized epidermal morphogenesis, and do permit analysis mature hair follicles (HFs) stem cell niches. To investigate Dsg3 antibody-induced adult epidermis at defined stages HF cycle, we developed...
Mutations in the cornified cell envelope protein loricrin have been reported recently some patients with Vohwinkel syndrome (VS) and progressive symmetric erythrokeratoderma (PSEK). To establish a causative relationship between mutations these diseases, we generated transgenic mice expressing COOH-terminal truncated form of that is similar to expressed VS PSEK patients. At birth, (ML.VS) exhibited an epidermal barrier dysfunction. 4 d after high-expressing animals showed generalized scaling...
Prohormone convertase 1 (PC1), mediating the proteolytic processing of neural and endocrine precursors, is thought to be regulated by neuroendocrine protein proSAAS. The PC1 inhibitory sequence mostly confined within a 10–12-amino acid segment near C terminus conserved human proSAAS contains critical KR<sup>244</sup> dibasic motif. Our results show that decapeptide proSAAS-(235–244)<sup>235</sup>VLGALLRVKR<sup>244</sup> most potent reversible competitive PC1-inhibitor (<i>K</i> <sub>i</sub>...