Journal ArticleJ Invest Dermatol · December 2024
UBE2N, a Lys63 ubiquitin-conjugating enzyme, plays critical roles in embryogenesis and immune system development and function. However, its roles in adult epithelial tissue homeostasis and pathogenesis are unclear. We generated conditional mouse models tha ...
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Journal ArticleJCI Insight · October 23, 2023
Aged skin is prone to viral infections, but the mechanisms responsible for this immunosenescent immune risk are unclear. We observed that aged murine and human skin expressed reduced levels of antiviral proteins (AVPs) and circadian regulators, including B ...
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Journal ArticleInt J Biol Macromol · August 1, 2023
Incidence of various cancers including melanoma continues to rise worldwide. While treatment options have expanded in the recent years, the benefit of these treatments suffer from short period of duration for many patients. Hence, new treatment options are ...
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Journal ArticleJCI insight · June 2023
Alloreactivity can drive autoimmune syndromes. After allogeneic hematopoietic stem cell transplantation (allo-HCT), chronic graft-versus-host disease (cGVHD), a B cell-associated autoimmune-like syndrome, commonly occurs. Because donor-derived B cells cont ...
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ConferencebioRxiv · April 18, 2023
Aged skin is prone to viral infections, but the mechanisms responsible for this immunosenescent immune risk are unclear. We observed that aged murine and human skin expressed reduced antiviral proteins (AVPs) and circadian regulators including Bmal1 and Cl ...
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Journal ArticleNat Commun · October 4, 2022
Some G protein-coupled receptor (GPCR) ligands act as "biased agonists" that preferentially activate specific signaling transducers over others. Although GPCRs are primarily found at the plasma membrane, GPCRs can traffic to and signal from many subcellula ...
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Journal ArticleBio Protoc · September 20, 2022
The ex vivo experimentation with surgically discarded human skin represents a unique methodology amenable for mechanism and pharmacologic agent studies without the involvement of human subjects. Here, we describe a protocol that includes preparation, cultu ...
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Journal ArticleJ Invest Dermatol · August 2022
The skin serves as the interface between the body and the environment and plays a fundamental role in innate antimicrobial host immunity. Antiviral proteins (AVPs) are part of the innate host defense system and provide protection against viral pathogens. H ...
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Journal ArticleStem Cell Reports · March 8, 2022
Skin tissue regeneration after injury involves the production and integration of signals by stem cells residing in hair follicles (HFSCs). Much remains unknown about how specific wound-derived factors modulate stem cell contribution to hair growth. We demo ...
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Journal ArticleFront Oncol · 2022
Autophagy is characterized as a cytoprotective process and inhibition of autophagy with medicinally active agents, such as chloroquine (CQ) is proposed as a prospective adjuvant therapy for cancer. Here, we examined the preclinical effects of CQ combined w ...
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Journal ArticleJOM · December 1, 2021
The delivery of drugs or vaccines using hollow needles involves a “poke and flow” approach, which involves the movement of the drug or vaccine through the bore of a hollow needle. In this paper, hollow needle arrays were created out of the fluoropolymer po ...
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Journal ArticleMRS Communications · December 1, 2021
This study evaluated the structural and skin penetration properties of solid microneedle arrays made by digital light processing-based 3D printing of polytetrafluoroethylene. Confocal laser scanning microscopy and scanning electron microscopy revealed that ...
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Journal ArticleJ Invest Dermatol · October 2021
UVR and immunosuppression are major risk factors for cutaneous squamous cell carcinoma (cSCC). Regulatory T cells promote cSCC carcinogenesis, and in other solid tumors, infiltrating regulatory T cells and CD8+ T cells express ectonucleoside triphosphate d ...
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Journal ArticleJID Innov · September 2021
Increased breakdown of glucose through glycolysis in both aerobic and anaerobic conditions is a hallmark feature of mammalian cancer and leads to increased production of L-lactate. The high-level lactate present within the tumor microenvironment is reused ...
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Journal ArticleGastroenterology · July 2021
BACKGROUND & AIMS: Limited understanding of pruritus mechanisms in cholestatic liver diseases hinders development of antipruritic treatments. Previous studies implicated lysophosphatidic acid (LPA) as a potential mediator of cholestatic pruritus. METHODS: ...
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Journal ArticleSci Rep · June 24, 2021
The current study is aimed at preparing light-driven novel functional AgNPs- bio-hydrogel and evaluating anticancer potency against human melanoma cells. With an average size of 16-18 nm, the hydrogel nano-silver particle composite (AgNPs@C_MA_O) was synth ...
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Journal ArticleFront Med (Lausanne) · 2021
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent abscesses, nodules, and sinus tracts in areas of high hair follicle and sweat gland density. These sinus tracts can present with purulent drainage and scar form ...
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Journal ArticleFront Immunol · 2021
Crosstalk between T cells, dendritic cells, and macrophages in temporal leukocyte clusters within barrier tissues provides a new concept for T cell activation in the skin. Activated T cells from these leukocyte clusters play critical roles in the efferent ...
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Journal ArticleInfect Immun · August 19, 2020
C-type lectin receptors (CLRs) play key roles in antifungal defense. CLR-induced NF-κB is central to CLR functions in immunity, and thus, molecules that control the amplitude of CLR-induced NF-κB could profoundly influence host defense against fungal patho ...
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Journal ArticleCells · April 2, 2020
The c-Jun N-terminal kinases (JNKs), with its members JNK1, JNK2, and JNK3, is a subfamily of (MAPK) mitogen-activated protein kinases. JNK signaling regulates a wide range of cellular processes, including cell proliferation, differentiation, survival, apo ...
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Chapter · November 8, 2019
Upon neoplastic transformation, melanoma is intrinsically prone to metastasis, which marks the most dangerous aspect of the disease and dubs it one of the most challenging cancers to treat. BRAF/MEK oncokinase inhibitors and immunotherapies have shown cons ...
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Journal ArticleJ Tissue Eng Regen Med · September 2019
De novo skin regeneration with human keratinocytes amplified in culture is a life-saving procedure for patients with extensive skin loss and chronic wounds. It also provides a valuable platform for gene function and therapeutic assessments. Nevertheless, t ...
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Journal ArticleCancer Res · November 15, 2018
UBE2N is a K63-specific ubiquitin conjugase linked to various immune disorders and cancer. Here, we demonstrate that UBE2N and its partners UBE2V1 and UBE2V2 are highly expressed in malignant melanoma. Silencing of UBE2N and its partners significantly decr ...
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Journal ArticleOncogenesis · July 31, 2017
Mucosa-associated lymphoma antigen 1 (MALT1) is a lymphoma oncogene that regulates signal transduction as a paracaspase and an adaptor protein. Yet, the role of MALT1 in other solid cancers such as melanoma is not well-understood. Here, we demonstrate that ...
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Chapter · June 28, 2017
Skin constitutes the largest biological barrier that protects from dehydration and mechanical injury, environmental toxins and microbes, and participates in immune responses. The epidermis of the skin is comprised of multilayered and stratified epithelial ...
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Chapter · June 20, 2017
Animal Models for the Study of Human Disease, Second Edition, provides needed information on model sharing, animal alternatives, animal ethics and access to databanks of models, bringing together common descriptions of models for busy ... ...
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Journal ArticleJ Invest Dermatol · April 2017
Mascarenhas et al. report that TRPV4 expression is upregulated in mast cells in response to the proteolytic cathelicidin fragment LL37 in a murine rosacea model and that TRPV4 loss of function attenuates mast cell degranulation. These findings render TRPV4 ...
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Journal ArticleJ Invest Dermatol · February 2017
Loss of function of KIND1, a cytoskeletal protein involved in β1-integrin function, causes Kindler syndrome, a genetic disease characterized by skin fragility, photosensitivity, and increased risk of squamous cell carcinoma. Dysregulation of β1-integrin un ...
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Journal ArticleInt J Bioprint · 2017
Transdermal delivery of amphotericin B, a pharmacological agent with activity against fungi and parasitic protozoa, is a challenge since amphotericin B exhibits poor solubility in aqueous solutions at physiologic pH values. In this study, we have used a la ...
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Journal ArticleJCI Insight · July 21, 2016
The deubiquitinase-encoding gene Cyld displays a dominant genetic linkage to a wide spectrum of skin-appendage tumors, which could be collectively designated as CYLD mutant-syndrome (CYLDm-syndrome). Despite recent advances, little is understood about the ...
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Journal ArticleOncotarget · June 7, 2016
FRA1 (Fos-like antigen 1) is highly expressed in many epithelial cancers including squamous cell carcinoma of the skin (cSCC) and head and neck (HNSCC). However, the functional importance and the mechanisms mediating FRA1 function in these cancers are not ...
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Journal ArticleJ Biol Chem · May 6, 2016
TRPV4 ion channels function in epidermal keratinocytes and in innervating sensory neurons; however, the contribution of the channel in either cell to neurosensory function remains to be elucidated. We recently reported TRPV4 as a critical component of the ...
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Journal ArticleJOM (1989) · April 2016
Itraconazole is a triazole agent that is routinely used for treatment of nail infections and other fungal infections. Recent studies indicate that itraconazole can also inhibit the growth of basal cell carcinoma (BCC) through suppression of the Sonic Hedge ...
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Journal ArticleJ Biomed Opt · May 2015
We demonstrate a multimodal approach that combines a pump-probe with confocal reflectance and multiphoton autofluorescence microscopy. Pump-probe microscopy has been proven to be of great value in analyzing thin tissue sections of pigmented lesions, as it ...
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Journal ArticleJ Invest Dermatol · April 2015
Mice with epidermal deletion of JunB transcription factor displayed a psoriasis-like inflammation. The relevance of these findings to humans and the mechanisms mediating JunB function are not fully understood. Here we demonstrate that impaired JunB functio ...
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ConferenceProgress in Biomedical Optics and Imaging - Proceedings of SPIE · January 1, 2015
Pump-probe microscopy is a multiphoton technique that generates molecular contrast from absorptive pigments, such as melanin. It holds the potential to be used as a non-invasive screening tool to discern whether a given early-stage melanoma has acquired th ...
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Journal ArticleJ Invest Dermatol · September 2014
This commentary on an exciting new study (Fusi et al., 2014) puts the finding of TRPV4 downregulation in several nonmelanoma skin cancers into context. The original paper point toward possible use of TRPV4 as dermatopathologic marker, also toward the possi ...
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Journal ArticleClin Exp Dermatol · October 2013
A number of Rho-kinase inhibitors have been developed for various clinical applications. We examined the effects of the Rho-kinase inhibitor Y27632 on keratinocyte proliferation and migration, and found that it promoted primary human keratinocyte prolifera ...
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Journal ArticleJ Invest Dermatol · January 2013
The molecular mechanisms mediating cylindromatosis (CYLD) tumor suppressor function appear to be manifold. Here, we demonstrate that, in contrast to the increased levels of phosphorylated c-Jun NH(2)-terminal kinase (pJNK), CYLD was decreased in a majority ...
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Journal ArticleJournal of Investigative Dermatology · 2013
The molecular mechanisms mediating cylindromatosis (CYLD) tumor suppressor function appear to be manifold. Here, we demonstrate that, in contrast to the increased levels of phosphorylated c-Jun NH 2 -terminal kinase (pJNK), CYLD was decreased in a majority ...
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Journal ArticleProgress in Biomedical Optics and Imaging - Proceedings of SPIE · April 16, 2012
A growing number of dermatologists and pathologists are concerned that the rapidly rising incidence of melanoma reflects not a true 'epidemic' but an increasing tendency to overdiagnose pigmented lesions. Addressing this problem requires both a better unde ...
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Journal ArticleCancer Research · April 15, 2012
AbstractRationale The diagnosis of melanoma is based on clinical identification followed by histopathologic confirmation. Surgical excision remains the mainstay for a suspicious lesion that will be evaluated ...
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Journal ArticleAm J Cancer Res · 2012
The c-Jun N-terminal Kinases (JNK), along with Erk and p38, constitute the principle members of the mitogen-activated protein kinase (MAPK) family. JNK functions primarily through AP1 family transcription factors to regulate a plethora of cellular processe ...
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Journal ArticleCancer Prev Res (Phila) · June 2011
CYLD has been recognized as a tumor suppressor due to its dominant genetic linkage to multiple types of epidermal tumors and a range of other cancers. The molecular mechanisms governing CYLD control of skin cancer are still unclear. Here, we showed that K1 ...
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Journal ArticleBiomed Opt Express · June 1, 2011
We performed epi-mode pump-probe imaging of melanin in excised human pigmented lesions and both hemoglobin and melanin in live xenograft mouse melanoma models to depths greater than 100 µm. Eumelanin and pheomelanin images, which have been previously demon ...
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Journal ArticleJ Invest Dermatol · May 2011
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Deregulation of the activator protein 1 (AP1) family gene regulators has been implicated in a wide range of diseases, including cancer. In this study we report that c-Jun was activated in human squamous cell carcinoma (SCC) and coexpression of c-Jun with o ...
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Journal ArticleCell Adh Migr · 2011
In addition to its well-defined role as an antagonist in apoptosis, we propose that BCL2 may act as an intracellular suppressor of cell motility and adhesion under certain conditions. Our evidence shows that, when over-expressed in both cancer and non-canc ...
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Journal ArticleCancer Res · April 15, 2010
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The c-Jun NH(2)-terminal kinase (JNK) signaling cascade has been implicated in a wide range of diseases, including cancer. It is unclear how different JNK proteins contribute to human cancer. Here, we report that JNK2 is activated in more than 70% of human ...
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Journal ArticleCell Res · April 2010
BCL2 is best known as a multifunctional anti-apoptotic protein. However, little is known about its role in cell-adhesive and motility events. Here, we show that BCL2 may play a role in the regulation of cell adhesion, spreading, and motility. When BCL2 was ...
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Journal ArticleGenes Dev · December 15, 2007
Aging is characterized by specific alterations in gene expression, but their underlying mechanisms and functional consequences are not well understood. Here we develop a systematic approach to identify combinatorial cis-regulatory motifs that drive age-dep ...
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Journal ArticleCancer Res · April 15, 2007
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The tumor necrosis factor alpha receptor (TNFR1) activates downstream effectors that include the mitogen-activated protein kinase kinase 7 (MKK7)/c-Jun-NH(2)-kinase (JNK)/activator protein 1 (AP1) cascade. Here, we report that JNK is activated in a majorit ...
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Journal ArticleJ Cell Biol · February 14, 2005
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Nuclear factor kappaB (NF-kappaB) mediates homeostatic growth inhibition in the epidermis, and a loss of NF-kappaB function promotes proliferation and oncogenesis. To identify mechanisms responsible for these effects, we impaired NF-kappaB action in the ep ...
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Journal ArticleGenes Dev · January 1, 2004
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NF-kappaB inhibition promotes epidermal tumorigenesis; however, whether this reflects an underlying role in homeostasis or a special case confined to neoplasia is unknown. Embryonic lethality of mice lacking NF-kappaB RelA has hindered efforts to address t ...
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Journal ArticleJ Immunol · November 1, 2003
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In humans and in mice, control of the intracellular pathogen, Mycobacterium tuberculosis (Mtb), requires IFN-gamma. Although the adaptive immune response results in production of substantial amounts of IFN-gamma in response to Mtb, the immune response is u ...
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Journal ArticleOncogene · April 3, 2003
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NF-kappa B regulates normal and pathological processes, including neoplasia, in a tissue-context-dependent manner. In skin, NF-kappa B is implicated in epidermal homeostasis as well as in the pathogenesis of squamous cell carcinoma; however, its function i ...
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Journal ArticleNature · February 6, 2003
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The nuclear factor NF-kappaB and oncogenic Ras can alter proliferation in epidermis, the most common site of human cancer. These proteins are implicated in epidermal squamous cell carcinoma in mice, however, the potential effects of altering their function ...
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Journal ArticleJ Cell Sci · December 1999
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SP85 is a multidomain protein of the Dictyostelium spore coat whose C-terminal region binds cellulose in vitro. To map domains critical for localizing SP85 and for binding to other proteins in vivo, its N- and C-terminal regions, and a hybrid fusion of the ...
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Journal ArticleBiochemistry · July 28, 1998
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The spore coat of Dictyostelium contains nine different proteins and cellulose. Interactions between protein and cellulose were investigated using an in vitro binding assay. Proteins extracted from coats with urea and 2-mercaptoethanol could, after removal ...
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Journal ArticleMicrobiology (Reading) · August 1996
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Highly purified spore coats of Dictyostelium discoideum each contained about 5 x 10(6) protein molecules as determined by amino acid composition analysis. By two-dimensional gel electrophoresis the coats were found to contain nine major-abundance and numer ...
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