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Item Staphylococcus δ-toxin promotes mouse allergic skin disease by inducing mast cell degranulation(Springer Nature, 2013) Nakamura, Yuumi; Oscherwitz, Jon; Cease, Kemp B.; Chan, Susana M.; Muñoz-Planillo, Raul; Hasegawa, Mizuho; Villaruz, Amer E.; Cheung, Gordon Y. C.; McGavin, Martin J.; Travers, Jeffrey B.; Otto, Michael; Inohara, Naohiro; Núñez, Gabriel; Dermatology, School of MedicineAtopic dermatitis is a chronic inflammatory skin disease that affects 15-30% of children and approximately 5% of adults in industrialized countries. Although the pathogenesis of atopic dermatitis is not fully understood, the disease is mediated by an abnormal immunoglobulin-E immune response in the setting of skin barrier dysfunction. Mast cells contribute to immunoglobulin-E-mediated allergic disorders including atopic dermatitis. Upon activation, mast cells release their membrane-bound cytosolic granules leading to the release of several molecules that are important in the pathogenesis of atopic dermatitis and host defence. More than 90% of patients with atopic dermatitis are colonized with Staphylococcus aureus in the lesional skin whereas most healthy individuals do not harbour the pathogen. Several staphylococcal exotoxins can act as superantigens and/or antigens in models of atopic dermatitis. However, the role of these staphylococcal exotoxins in disease pathogenesis remains unclear. Here we report that culture supernatants of S. aureus contain potent mast-cell degranulation activity. Biochemical analysis identified δ-toxin as the mast cell degranulation-inducing factor produced by S. aureus. Mast cell degranulation induced by δ-toxin depended on phosphoinositide 3-kinase and calcium (Ca(2+)) influx; however, unlike that mediated by immunoglobulin-E crosslinking, it did not require the spleen tyrosine kinase. In addition, immunoglobulin-E enhanced δ-toxin-induced mast cell degranulation in the absence of antigen. Furthermore, S. aureus isolates recovered from patients with atopic dermatitis produced large amounts of δ-toxin. Skin colonization with S. aureus, but not a mutant deficient in δ-toxin, promoted immunoglobulin-E and interleukin-4 production, as well as inflammatory skin disease. Furthermore, enhancement of immunoglobulin-E production and dermatitis by δ-toxin was abrogated in Kit(W-sh/W-sh) mast-cell-deficient mice and restored by mast cell reconstitution. These studies identify δ-toxin as a potent inducer of mast cell degranulation and suggest a mechanistic link between S. aureus colonization and allergic skin disease.Item Structure Based Identification and Characterization of Flavonoids That Disrupt Human Papillomavirus-16 E6 Function(Public Library of Science, 2013-12-23) Cherry, Jonathan J.; Rietz, Anne; Malinkevich, Anna; Liu, Yuqi; Xie, Meng; Bartolowits, Matthew; Davisson, V. Jo; Baleja, James D.; Androphy, Elliot J.; Dermatology, School of MedicineExpression and function of the human papillomavirus (HPV) early protein 6 (E6) is necessary for viral replication and oncogenesis in cervical cancers. HPV E6 targets the tumor suppressor protein p53 for degradation. To achieve this, "high-risk" HPV E6 proteins bind to and modify the target specificity of the ubiquitin ligase E6AP (E6 associated protein). This E6-dependent loss of p53 enables the virus to bypass host cell defenses and facilitates virally induced activation of the cell cycle progression during viral replication. Disruption of the interaction between E6 and E6AP and stabilization of p53 should decrease viability and proliferation of HPV positive cells. A new in vitro high-throughput binding assay was developed to assay binding between HPV-16 E6 and E6AP and to identify compounds that inhibit this interaction. The compound luteolin emerged from the screen and a library of novel flavones based on its structure was synthesized and characterized using this in vitro binding assay. The compounds identified in this study disrupt the E6/E6AP interaction, increase the levels of p53 and p21(Cip1/Waf1), and decrease proliferation of HPV positive cell lines. The new class of flavonoid E6 inhibitors displays a high degree of specificity for HPV positive cells. Docking analyses suggest that these compounds bind in a hydrophobic pocket at the interface between E6 and E6AP and mimic the leucines in the conserved α-helical motif of E6AP. The activity and specificity of these compounds represent a promising new lead for development as an antiviral therapy in the treatment of HPV infection and cervical cancer.Item Dental Abnormalities in Congenital Ichthyoses: Case Report and Review of the Literature(Wiley, 2025) Maarouf, Sarah; Clark, Marie; Chen, Anthony; Haggstrom, Anita; Dermatology, School of MedicineWe describe a 1-day old female with features of keratitis-ichthyosis-deafness (KID) syndrome and natal teeth. Genetic analysis confirmed GJB2 263C and A88V de novo pathogenic variants consistent with KID syndrome. Natal teeth were promptly extracted to avoid the risk of aspiration. This review describes subsets of ichthyoses that have been reported in association with dental anomalies, highlighting the need for early dental referral and importance of long-term follow-up.Item Incidence of nonmelanoma skin cancer in patients with vitiligo who applied ruxolitinib cream(Wiley, 2025) Ezzedine, Khaled; Wolkerstorfer, Albert; Wei, Shaoceng; Korba, Abdelhak Amara; Kornacki, Deanna; Rosmarin, David; Dermatology, School of MedicineItem Pten loss induces autocrine FGF signaling to promote skin tumorigenesis(Elsevier, 2014) Hertzler-Schaefer, Kristina; Mathew, Grinu; Somani, Ally-Khan; Tholpady, Sunil; Kadakia, Madhavi P.; Chen, Yiping; Spandau, Dan F.; Zhang, Xin; Dermatology, School of MedicineInactivation of the Pten tumor suppressor negatively regulates the PI3K-mTOR pathway. In a model of cutaneous squamous cell carcinoma (SCC), we demonstrate that deletion of Pten strongly elevates Fgf10 protein levels without increasing Fgf10 transcription in vitro and in vivo. The translational activation of Fgf10 by Pten deletion is reversed by genetic disruption of the mTORC1 complex, which also prevents skin tumorigenesis in Pten mutants. We further show that ectopic expression of Fgf10 causes skin papillomas, whereas Pten deletion-induced skin tumors are inhibited by epidermal deletion of Fgfr2. Collectively, our data identify autocrine activation of FGF signaling as an essential mechanism in promoting Pten-deficient skin tumors.Item Response to Wang et al's limitations and risks of custom GPTs in dermatology. Comment on “ReconGPT: A novel artificial intelligence tool and its potential use in post-Mohs reconstructive decision-making”(Elsevier, 2025) Jairath, Neil; Manduca, Sophia; Que, Syril Keena T.; Dermatology, School of MedicineItem Systemic Platelet-activating Factor Receptor Activation Augments Experimental Lung Tumor Growth and Metastasis(Sage, 2014-06-19) Hackler, Patrick C.; Reuss, Sarah; Konger, Raymond L.; Travers, Jeffrey B.; Sahu, Ravi P.; Dermatology, School of MedicinePro-oxidative stressors including cigarette smoke (CS) generate novel lipids with platelet-activated factor-receptor (PAF-R) agonistic activity mediate systemic immunosuppression, one of the most recognized events in promoting carcinogenesis. Our previous studies have established that these oxidized-PAF-R-agonists augment murine B16F10 melanoma tumor growth in a PAF-R-dependent manner because of its effects on host immunity. As CS generates PAF-R agonists, the current studies sought to determine the impact of PAF-R agonists on lung cancer growth and metastasis. Using the murine Lewis Lung Carcinoma (LLC1) model, we demonstrate that treatment of C57BL/6 mice with a PAF-R agonist augments tumor growth and lung metastasis in a PAF-R-dependent manner as these findings were not seen in PAF-R-deficient mice. Importantly, this effect was because of host rather than tumor cells PAF-R dependent as LLC1 cells do not express functional PAF-R. These findings indicate that experimental lung cancer progression can be modulated by the PAF system.Item Skin resurfacing procedures: new and emerging options(Dove Press, 2014-08-28) Loesch, Mathew M.; Somani, Ally-Khan; Kingsley, Melanie M.; Travers, Jeffrey B.; Spandau, Dan F.; Dermatology, School of MedicineThe demand for skin resurfacing and rejuvenating procedures has progressively increased in the last decade and has sparked several advances within the skin resurfacing field that promote faster healing while minimizing downtime and side effects for patients. Several technological and procedural skin resurfacing developments are being integrated into clinical practices today allowing clinicians to treat a broader range of patients’ skin types and pathologies than in years past, with noteworthy outcomes. This article will discuss some emerging and developing resurfacing therapies and treatments that are present today and soon to be available.Item Drug Reaction With Eosinophilia and Systemic Symptoms to Vancomycin-Laden Cement Space: A Case Report(Springer Nature, 2025-01-03) Chalasani, Sai; Mannam, Harshita; Alomari, Ahmed K.; Rahnama-Moghadam, Sahand; Dermatology, School of MedicineDrug reaction with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous adverse drug reaction mediated by a complex immune response. Vancomycin is a known cause of DRESS, and cases are often attributed to intravenous exposure. Vancomycin-laden bone cements deliver high concentrations of the drug locally with low to undetectable systemic levels. Despite trace systemic concentrations, cement spacers have been reported to cause systemic reactions ranging from organ failure to diffuse cutaneous eruptions. A patient receiving intravenous (IV) and local vancomycin, via bone cement, experienced symptom resolution only after the vancomycin-eluting bone cement was removed, which was done after the IV vancomycin had been stopped. This suggests that the vancomycin eluted from the local bone cement may be sufficient to maintain the immune response mediating DRESS syndrome. In patients who experience persistent symptoms despite discontinuing systemic drug exposure, clinicians should consider eliminating all sources of the causative drug.Item The Role of Virtual and Augmented Reality in Advancing Drug Discovery in Dermatology(Wiley, 2025) Kircik, Leon; Goldust, Mohamad; Dermatology, School of Medicine