A5054246236- Archaeology and Natural History
- Cultural Heritage Management and Preservation
- American Environmental and Regional History
- Historical and Cultural Archaeology Studies
- Wnt/β-catenin signaling in development and cancer
- Cellular Mechanics and Interactions
- Skin and Cellular Biology Research
- Conservation Techniques and Studies
- Archaeology and ancient environmental studies
- Hippo pathway signaling and YAP/TAZ
- Transportation Safety and Impact Analysis
- Underground infrastructure and sustainability
- Geotechnical Engineering and Underground Structures
- Genetic and rare skin diseases.
- Engineering and Material Science Research
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- Structural Engineering and Vibration Analysis
- Archaeological Research and Protection
- Wildlife Ecology and Conservation
- Food Safety and Hygiene
- Botany, Ecology, and Taxonomy Studies
- Hedgehog Signaling Pathway Studies
- 3D Printing in Biomedical Research
- Wine Industry and Tourism
Northwestern University
2009-2024
University of Chicago
2016-2022
Chicago Institute for Psychoanalysis
2021
Albany Medical Center Hospital
2004-2007
Dsg1 (desmoglein 1) is a member of the cadherin family Ca2+-dependent cell adhesion molecules that first expressed in epidermis as keratinocytes transit out basal layer and becomes concentrated uppermost layers this stratified epithelium. In study, we show not only required for maintaining epidermal tissue integrity superficial but also supports keratinocyte differentiation suprabasal morphogenesis. lacking N-terminal ectodomain residues remained capable promoting differentiation. Moreover,...
Genetic disorders of the Ras/MAPK pathway, termed RASopathies, produce numerous abnormalities, including cutaneous keratodermas. The desmosomal cadherin, desmoglein-1 (DSG1), promotes keratinocyte differentiation by attenuating MAPK/ERK signaling and is linked to striate palmoplantar keratoderma (SPPK). This raises possibility that defects associated with SPPK RASopathies share certain molecular faults. To identify intermediates responsible for executing inhibition ERK DSG1, we conducted a...
Severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome is a recently recognized caused by mutations in the desmoglein 1 gene (DSG1). To date, only 3 families have been reported.We studied new case of SAM known to no DSG1 detail clinical, histopathologic, immunofluorescent, ultrastructural phenotype identify underlying molecular mechanisms this rare genodermatosis.Histopathologic, electron microscopy, immunofluorescent studies were performed. Whole-exome sequencing data...
Desmosomes are one of four intercellular junctions present on the lateral side neighboring polarized epithelial cells. Tight and adherens (AJs) restricted to apical domain, where they form barrier organize cortical actin, respectively. found subjacent AJs more widely distributed along membranes. By tethering intermediate filament (IF) cytoskeleton plasma membrane, these strongly adhesive further enhance their force-resisting mechanical properties (see Poster, panels 1 3). Interspersed among...
Adhesion between cells is established by the formation of specialized intercellular junctional complexes, such as desmosomes. Desmosomes comprise two members cadherin superfamily cell adhesion proteins, desmocollin (Dsc) and desmoglein (Dsg), but their combinatorial roles in desmosome assembly not understood. To uncouple from other cell-cell we used micro-patterned substrates Dsc2aFc and/or Dsg2Fc collagen IV; show that Dsc2aFc, Dsg2Fc, was necessary sufficient to recruit desmosome-specific...
The epidermis is a multi-layered epithelium that serves as barrier against water loss and environmental insults. Its morphogenesis occurs through tightly regulated program of biochemical architectural changes during which basal cells commit to differentiate move towards the skin's surface. Here, we reveal an unexpected role for vertebrate cadherin desmoglein 1 (Dsg1) in remodeling actin cytoskeleton promote transit into suprabasal layer process delamination, one mechanism epidermal...
Although much is known about signaling factors downstream of Rho GTPases that contribute to epidermal differentiation, little which upstream regulatory proteins (guanine nucleotide exchange [GEFs] or GTPase-activating [GAPs]) are involved in coordinating keratinocytes. Here we identify the GEF breakpoint cluster region (Bcr) as a major regulator RhoA activity, stress fibers, and focal adhesion formation Loss Bcr reduced expression multiple markers differentiation (such desmoglein-1 [Dsg1],...
Disorders linked to heterozygous variants occupy a continuum in terms of the timing and severity phenotypic emergence. An important question regarding this variability entails effect stress has on residual protein function. Using Darier disease (DD), caused by SERCA2 calcium pump, as model, we uncovered potential connection between extrinsic pathogenesis. The skin lesions characteristic DD entail loss intercellular adhesion rarely appear pre-adolescence, suggesting that factors beyond...
An effective epidermal barrier requires structural and functional integration of adherens junctions, tight gap junctions (GJ), desmosomes. Desmosomes govern integrity while GJs facilitate small molecule transfer across cell membranes. Some patients with severe dermatitis, multiple allergies, metabolic wasting (SAM) syndrome, caused by biallelic desmoglein 1 (DSG1) mutations, exhibit skin lesions reminiscent erythrokeratodermia variabilis, mutations in connexin (Cx) genes. We, therefore,...
Darier, Hailey-Hailey, and Grover diseases are rare acantholytic skin diseases. While these have different underlying causes, they share defects in cell-cell adhesion the epidermis desmosome organization. To better understand mechanisms leading to disease conditions, we performed RNA-seq on lesional samples from patients. The transcriptomic profiles of were found a remarkable overlap, which did not extend other common inflammatory Analysis enriched pathways showed shared increase...
Cell junctions are scaffolds that integrate mechanical and chemical signaling. We previously showed a desmosomal cadherin promotes keratinocyte differentiation in an adhesion-independent manner by dampening Epidermal Growth Factor Receptor (EGFR) activity. Here we identify potential mechanism which desmosomes assist the de-neddylating COP9 signalosome (CSN) attenuating EGFR through association between Cops3 subunit of CSN components, Desmoglein1 (Dsg1) Desmoplakin (Dp), to promote epidermal...
Epidermolytic ichthyosis (EI) is a rare disorder of cornification caused by mutations in KRT1 and KRT10, encoding two suprabasal epidermal keratins. Because the variable clinical features severity disease, histopathology often required to correctly direct molecular analysis. EI characterized hyperkeratosis vacuolar degeneration upper epidermis, also known as epidermolytic hyperkeratosis, hence name disease. In current report, authors describe members 2 families presenting with consistent EI....
Although implicated in adhesion, only a few studies address how the actin assembly factors guide cell positioning multicellular tissues. The formin, Dia1, localizes to proliferative basal layer of epidermis. In organotypic cultures, Dia1 depletion reduced density and resulted stratified tissues with disorganized differentiation markers. Since crowding induces epidermal tissues, we hypothesized that is essential reach densities amenable before or during stratification. Consistent this, forced...
Abstract Although implicated in adhesion, few studies address how actin assembly factors guide cell positioning multicellular tissue. The formin, Dia1, localizes to the proliferative basal layer of epidermis. In organotypic cultures, Dia1 depletion reduced density and resulted stratified tissue with disorganized differentiation markers. Since crowding induces epidermal tissue, we hypothesized that allows cells reach densities amenable prior stratification. Consistent this hypothesis, forced...
Abstract Tissue morphogenesis often arises from the culmination of discrete changes in cell-cell junction behaviors, namely ratcheted contractions that lead to collective cellular rearrangements. Mechanochemical signaling form RhoA underlies these contractions, which occur asymmetrically as one highly motile vertex contracts toward a relatively less tricellular vertex. The underlying mechanisms driving asymmetric movement remains unknown. Here, we use optogenetically controlled model...