- Psoriasis: Treatment and Pathogenesis
- Dermatology and Skin Diseases
- Cytokine Signaling Pathways and Interactions
- Angiogenesis and VEGF in Cancer
- Asthma and respiratory diseases
- Autoimmune Bullous Skin Diseases
- Axon Guidance and Neuronal Signaling
- T-cell and B-cell Immunology
- Lipid metabolism and disorders
- Urticaria and Related Conditions
- Simulation-Based Education in Healthcare
- Nerve injury and regeneration
- Retinoids in leukemia and cellular processes
- Cancer, Hypoxia, and Metabolism
- MicroRNA in disease regulation
- Neurogenesis and neuroplasticity mechanisms
- Atherosclerosis and Cardiovascular Diseases
- Monoclonal and Polyclonal Antibodies Research
- Cutaneous lymphoproliferative disorders research
- S100 Proteins and Annexins
- Food Security and Health in Diverse Populations
- Neuroscience of respiration and sleep
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Response and Inflammation
- Immune cells in cancer
Vanderbilt University Medical Center
2022-2025
Case Western Reserve University
2015-2024
Deakin University
2023-2024
Vanderbilt University
2024
Wellbeing of Women
2024
The University of Sydney
2024
University of Arkansas for Medical Sciences
2020-2023
Riley Hospital for Children
2022
Kuehne + Nagel (United Kingdom)
2022
Pfizer (United Kingdom)
2022
Highlights•BCCs arise primarily from stem cells within hair follicle and touch dome epithelia•Stem in the interfollicular epidermis do not efficiently form tumors•Innervation is required for Hedgehog signaling dome•Cutaneous nerves promote tumors arising mechanosensory nicheSummaryBasal cell carcinoma (BCC) characterized by frequent loss of PTCH1, leading to constitutive activation pathway. Although requirement BCC well established, identity disease-initiating compartments which they reside...
IL-1F6, IL-1F8, and IL-1F9 the IL-1R6(RP2) receptor antagonist IL-1F5 constitute a novel IL-1 signaling system that is poorly characterized in skin. To further characterize these cytokines healthy inflamed skin, we studied their expression control, uninvolved psoriasis, psoriasis plaque skin using quantitative RT-PCR immunohistochemistry. Expression of IL-1F5, -1F6, -1F8, -1F9 were increased 2 to 3 orders magnitude versus which was supported immunohistologically. Moreover, treatment with...
Abstract IL-17C is a functionally distinct member of the IL-17 family that binds receptor E/A to promote innate defense in epithelial cells and regulate Th17 cell differentiation. We demonstrate (not IL-17A) most abundant isoform lesional psoriasis skin (1058 versus 8 pg/ml; p < 0.006) localizes keratinocytes (KCs), endothelial (ECs), leukocytes. ECs stimulated with produce increased TNF-α KCs IL-17C/TNF-α similar inflammatory gene response patterns as those elicited by IL-17A/TNF-α,...
The IL-1 family members IL-36α (IL-1F6), IL-36β (IL-1F8), and IL-36γ (IL-1F9) the receptor antagonist IL-36Ra (IL-1F5) constitute a novel signaling system that is poorly understood. We now show these cytokines have profound effects on skin immune system. Treatment of human keratinocytes with IL-36 significantly increased expression CXCL1, CXCL8, CCL3, CCL5, CCL20, potent chemotactic agents for activated leukocytes, injected intradermally resulted in chemokine expression, leukocyte...
Psoriasis severity categories have been important tools for clinicians to use in treatment decisions as well determine eligibility criteria clinical studies. However, owing the heterogeneity of classifications and their lack consideration impact psoriasis involvement special areas or past history, patients may be miscategorized, which can lead undertreatment psoriasis.To develop a consensus statement on classification severity.A modified Delphi approach was developed by International Council...
Abstract The immunopathogenesis of psoriasis, a common chronic inflammatory disease the skin, is incompletely understood. Here we demonstrate, using combination single cell and spatial RNA sequencing, IL-36 dependent amplification IL-17A TNF responses in absence neutrophil proteases, which primarily occur within supraspinous layer psoriatic epidermis. We further show that subset SFRP2 + fibroblasts psoriasis contribute to immune network through transition pro-inflammatory state. fibroblast...
Lineal structures in biological tissue support a wide variety of physiological functions, including membrane stabilization, vascular perfusion, and cell-to-cell communication. In 1953, Smith Guttman demonstrated stereological method to estimate the total length density (Lv) linear objects based on random intersections with two-dimensional sampling probe. Several methods have been developed ensure required isotropy object-probe intersections, isotropic-uniform-random (IUR) sections,...
Development of a suitable mouse model would facilitate the investigation pathomechanisms underlying human psoriasis and also assist in development therapeutic treatments. However, while many models have been proposed, no single recapitulates all features disease, standardized validation criteria for not widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by psoriatic skin lesions with those that occur five (K5-Tie2,...
Imiquimod (IMQ) produces a cutaneous phenotype in mice frequently studied as an acute model of human psoriasis. Whether this depends on strain or sex has never been systematically investigated large scale. Such effects, however, could lead to conflicts among studies, while further impacting study outcomes and efforts translate research findings. RNA-seq was used evaluate the psoriasiform elicited by 6 days Aldara (5% IMQ) treatment both sexes seven mouse strains (C57BL/6 J (B6), BALB/cJ,...
Abstract Chronic inflammation is a critical component of atherogenesis, however, reliable human translational models aimed at characterizing these mechanisms are lacking. Psoriasis, chronic inflammatory skin disease associated with increased susceptibility to atherosclerosis, provides clinical model that can be utilized investigate the links between and atherosclerosis development. We sought key biological processes in psoriasis vascular tissue identify components may promote conditions....
IL-36 cytokines have recently emerged as mediators of inflammation in autoimmune conditions including psoriasis vulgaris (PsV) and generalized pustular (GPP). This study used RNA-seq to profile the transcriptome primary epidermal keratinocytes (KCs) treated with IL-1B, IL-36A, IL-36B or IL-36G. We identified some early IL-1B-specific responses (8 hours post-treatment), but nearly all late IL-1B were replicated by (24 post-treatment). Type I II interferon genes exhibited time-dependent...
Abstract The IL-17 family cytokines IL-17A and IL-17C drive the pathogenesis of psoriatic skin inflammation, anti–IL-17A Abs were recently approved to treat human psoriasis. Little is known about mechanisms that restrain cytokine-mediated signaling, particularly IL-17C. In this article, we show endoribonuclease MCP-1–induced protein 1 (MCPIP1; also as regnase-1) markedly upregulated in lesions. Similarly, MCPIP1 was overexpressed imiquimod (IMQ)-driven mouse model cutaneous inflammation....