21 results on '"Stephen Prouty"'
Search Results
2. Single-Soma Deep Rna Sequencing of Human DRG Neurons Reveals Novel Molecular and Cellular Mechanisms Underlying Somatosensation
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Huasheng Yu, Dmitry Usoskin, Saad S. Nagi, Yizhou Hu, Jussi Kupari, Otmane Bouchatta, Suna Li Cranfill, Yijing Su, You Lv, Hongjun Song, Guo-Li Ming, Stephen Prouty, John Seykora, Hao Wu, Minghong Ma, Håkan Olausson, Patrik Ernfors, and Wenqin Luo
- Subjects
Article - Abstract
The versatility of somatosensation arises from heterogenous human dorsal root ganglion (DRG) neurons. The critical information to decipher their functions, i.e., the soma transcriptome, is lacking due to technical difficulties. Here we developed a novel approach to isolate individual human DRG neuron somas for deep RNA sequencing (RNA-seq). On average, >9000 unique genes per neuron were detected, and 16 neuronal types were identified. Cross-species analyses revealed that touch-, cold-, and itch-sensing neuronal types were relatively conserved, while the pain-sensing neurons displayed marked divergence. Soma transcriptomes of human DRG neurons predicted novel functional features, which were confirmed using single-cellin vivoelectrophysiological recordings. These results support a close relationship the between physiological properties of human sensory afferents and molecular profiles uncovered by the single-soma RNA-seq dataset. In summary, by conducting single-soma RNA-seq of human DRG neurons, we generated an unprecedented neural atlas for human somatosensation.
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- 2023
3. METTL3 maintains epithelial homeostasis through m6A-dependent regulation of chromatin modifiers
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Alexandra M. Maldonado López, Sijia Huang, Gina Pacella, Eun Kyung Ko, Hui Shen, Julian Stoute, Morgan Sinkfield, Amy Anderson, Stephen Prouty, Hua-Bing Li, John T. Seykora, Kathy Fange Liu, and Brian C. Capell
- Abstract
The balance between epithelial stemness and differentiation requires the precise regulation of gene expression programs. Epitranscriptomic RNA modifications have been implicated in both epithelial development as well as cancers. However, the underlying mechanisms are poorly understood. Here, we show that deletion of the m6A methyltransferase, METTL3, impairs the m6A-mediated degradation of numerous mRNA transcripts encoding critical chromatin modifying enzymes, resulting in widespread gene expression abnormalities as well as both aberrant cutaneous and oral epithelial phenotypesin vivo. Collectively, these results offer new insights into a new layer of gene regulation within epithelial surface tissues and will inform future epitranscriptomic studies within epithelial cancer and developmental biology.
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- 2022
4. Stress vesicles are induced by acute mechanical force and precede the commitment of epidermal stem cells to terminal differentiation
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Sixia Huang, Paola Kuri, Jonathan Zou, Adriana Blanco, Maxwell Marshall, Gabriella Rice, Stephen Prouty, Tzvete Dentchev, Miriam Doepner, Joel D. Boerckel, Brian C. Capell, Todd W. Ridky, and Panteleimon Rompolas
- Abstract
The skin has a pronounced ability to adapt to physical changes in the environment by exhibiting plasticity at the cellular level. Transient mechanical deformations applied to the skin are accommodated without permanent changes to tissue structure. However, sustained physical stress induces long-lasting alterations in the skin, which are mediated by shifts in the fates of epidermal stem cells. To investigate this phenomenon, we implemented two-photon intravital imaging to capture the responses of epidermal cells when an acute mechanical force is applied to the live skin. We show that mechanical stress induces the formation of intracellular vesicles in epidermal stem cells, which are filled with extracellular fluid and gradually enlarge, causing the deformation of the cell nucleus. By lineage tracing analysis we demonstrate that the degree of nuclear deformation is linked to cell fate. Utilizing a fluorescent in vivo reporter, to capture intracellular calcium dynamics, we show that mechanical force induces a sustained increase in intracellular calcium within basal epidermal stem cells. Conditional deletion of Piezo1, a mechanosensitive ion channel, alters intracellular calcium dynamics and increases the number of stress vesicles in epidermal stem cells. Using a human skin xenograft model, we show that stress vesicles are a conserved phenomenon in mammalian skin. This study uncovers stress vesicles as key manifestations of the mechanism that regulates the fate of epidermal stem cells under conditions of mechanical stress, in which Piezo1 and calcium dynamics are also involved.
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- 2022
5. H3K36M provokes cellular plasticity to drive aberrant glandular formation and squamous carcinogenesis
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Eun Kyung Ko, Amy Anderson, Jonathan Zou, Sijia Huang, Sohyun Cho, Faizan Alawi, Stephen Prouty, Vivian Lee, Kai Ge, John T. Seykora, and Brian C. Capell
- Abstract
Epigenetic dysregulation is pervasive in cancer, frequently impairing normal tissue development and differentiation1. Beyond alterations in histone modifying enzymes, “oncohistone” mutations have been described across a variety of cancers2-4, although the in vivo effects and underlying mechanisms behind these observations have not been well- studied and remain unclear. Here, by inducing the in vivo expression of histone H3.3 carrying a lysine to methionine (K to M) mutation at position 36 (H3K36M) in self- renewing stratifying epithelial tissues, we show that the H3K36M oncohistone dramatically disrupts normal epithelial differentiation, leading to extensive tissue dysplasia characterized by a significant increase in mitotic, proliferative basal stem cells. Furthermore, this differentiation blockade promotes increased cellular plasticity and enrichment of alternate cell fates, and in particular the aberrant generation of excessive glandular tissue including both hypertrophic salivary, sebaceous, and meibomian glands. Upon carcinogen stress, H3K36M mice display markedly enhanced squamous tumorigenesis. These aberrant phenotypic and gene expression manifestations are associated with global loss of H3K36me2 and concomitant gain of H3K27me3. Collectively, these results have revealed a previously unknown critical role for H3K36 methylation in both the in vivo maintenance of proper epithelial cell fate decisions and the prevention of squamous carcinogenesis. Additionally, they suggest that H3K36 methylation modulation may offer new avenues for the regulation of numerous common disorders driven by over- or under-active glandular function.
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- 2022
6. NF-κB perturbation reveals unique immunomodulatory functions in Prx1
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Kang I, Ko, Jean J, Merlet, Brett P, DerGarabedian, Huang, Zhen, Yoko, Suzuki-Horiuchi, Matthew L, Hedberg, Eileen, Hu, Anh T, Nguyen, Stephen, Prouty, Faizan, Alawi, Matthew C, Walsh, Yongwon, Choi, Sarah E, Millar, Ashley, Cliff, Jonathon, Romero, Michael R, Garvin, John T, Seykora, Daniel, Jacobson, and Dana T, Graves
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Mice ,Artificial Intelligence ,Immunity ,NF-kappa B ,Animals ,respiratory system ,Fibroblasts ,Article ,Dermatitis, Atopic ,Skin - Abstract
Skin is composed of diverse cell populations that cooperatively maintain homeostasis. Upregulation of the Nuclear factor-kappa B pathway may lead to the development of chronic inflammatory disorders of the skin, but its role during the early events remains unclear. Through analysis of single cell RNA sequencing data via iterative Random Forest Leave One Out Prediction, an explainable artificial intelligence method, we identified an immunoregulatory role for a unique Prx1(+) fibroblast subpopulation. Disruption of Ikkb-NF-kB under homeostatic conditions in these fibroblasts paradoxically induced skin inflammation due to the overexpression of C-C Motif Chemokine Ligand 11 (CCL11, or eotaxin-1) characterized by eosinophil infiltration and a subsequent Th2 immune response. Because the inflammatory phenotype resembled that seen in human atopic dermatitis (AD), we examined validated human AD skin samples and found that human AD fibroblasts also over-expressed CCL11 and that perturbation of Ikkb-NFkB in primary human dermal fibroblasts upregulates CCL11. We also demonstrated that monoclonal antibody treatment against CCL11 was effective in reducing the eosinophilia and Th2 inflammation in a mouse model. Taken together, the murine model and human AD specimens point to dysregulated Prx1(+) fibroblasts as a previously unrecognized etiologic factor that may contribute to the pathogenesis of AD and suggest targeting CCL11 as a way to treat AD-like skin lesions.
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- 2022
7. NF-κB perturbation reveals unique immunomodulatory functions in Prx1 + fibroblasts that promote development of atopic dermatitis
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Kang I. Ko, Jean J. Merlet, Brett P. DerGarabedian, Huang Zhen, Yoko Suzuki-Horiuchi, Matthew L. Hedberg, Eileen Hu, Anh T. Nguyen, Stephen Prouty, Faizan Alawi, Matthew C. Walsh, Yongwon Choi, Sarah E. Millar, Ashley Cliff, Jonathon Romero, Michael R. Garvin, John T. Seykora, Daniel Jacobson, and Dana T. Graves
- Subjects
General Medicine ,respiratory system - Abstract
Skin is composed of diverse cell populations that cooperatively maintain homeostasis. Up-regulation of the nuclear factor κB (NF-κB) pathway may lead to the development of chronic inflammatory disorders of the skin, but its role during the early events remains unclear. Through analysis of single-cell RNA sequencing data via iterative random forest leave one out prediction, an explainable artificial intelligence method, we identified an immunoregulatory role for a unique paired related homeobox-1 (Prx1) + fibroblast subpopulation. Disruption of Ikkb –NF-κB under homeostatic conditions in these fibroblasts paradoxically induced skin inflammation due to the overexpression of C-C motif chemokine ligand 11 (CCL11; or eotaxin-1) characterized by eosinophil infiltration and a subsequent T H 2 immune response. Because the inflammatory phenotype resembled that seen in human atopic dermatitis (AD), we examined human AD skin samples and found that human AD fibroblasts also overexpressed CCL11 and that perturbation of Ikkb –NF-κB in primary human dermal fibroblasts up-regulated CCL11. Monoclonal antibody treatment against CCL11 was effective in reducing the eosinophilia and T H 2 inflammation in a mouse model. Together, the murine model and human AD specimens point to dysregulated Prx1 + fibroblasts as a previously unrecognized etiologic factor that may contribute to the pathogenesis of AD and suggest that targeting CCL11 may be a way to treat AD-like skin lesions.
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- 2022
8. Harnessing Augmented Reality and CT to Teach First-Year Medical Students Head and Neck Anatomy
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Joanna K. Weeks, Stephen Prouty, Jina Pakpoor, Neal A. Rubinstein, B. Park, Nicole J. Robinson, and Arun C. Nachiappan
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medicine.medical_specialty ,business.product_category ,Recall ,Headset ,education ,Article ,Mixed reality ,Session (web analytics) ,030218 nuclear medicine & medical imaging ,Visualization ,Test (assessment) ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Laptop ,medicine ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Augmented reality ,Psychology ,business - Abstract
RATIONALE AND OBJECTIVES: Three-dimensional (3D) visualization has been shown to benefit new generations of medical students and physicians-in-training in a variety of contexts. However, there is limited research directly comparing student performance after using 3Dtools to those using two-dimensional (2D) screens. MATERIALS AND METHODS: A CT was performed on a donated cadaver and a 3D CT hologram was created. A total of 30 first-year medical students were randomly assigned into two groups to review head and neck anatomy in a teaching session that incorporated CT. The first group used an augmented reality headset, while the second group used a laptop screen. The students were administered a five-question anatomy test before and after the session. Two-tailed t-tests were used for statistical comparison of pretest and posttest performance within and between groups. A feedback survey was distributed for qualitative data. RESULTS: Pretest vs. posttest comparison of average percentage of questions answered correctly demonstrated both groups showing significant in-group improvement (p < 0.05), from 59% to 95% in the augmented reality group, and from 57% to 80% in the screen group. Between-group analysis indicated that posttest performance was significantly better in the augmented reality group (p = 0.022, effect size = 0.73). CONCLUSION: Immersive 3D visualization has the potential to improve short-term anatomic recall in the head and neck compared to traditional 2D screen-based review, as well as engage millennial learners to learn better in anatomy laboratory. Our findings may reflect additional benefit gained from the stereoscopic depth cues present in augmented reality-based visualization.
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- 2020
9. Srcasm Regulates Tyrosine Kinases in Skin Cancer: Implications for Precision Medicine
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Tzvete Denchev, Xiaoping Yang, C. O'Day, Christine Marshall, Hasan Bashir, Stephen Prouty, Vivian S. Lee, Hiroshi Maeno, and John T. Seykora
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business.industry ,Incidence (epidemiology) ,Actinic keratosis ,Cancer ,Cell Biology ,Dermatology ,General Medicine ,SRC Family Tyrosine Kinase ,medicine.disease ,Precision medicine ,medicine ,Cancer research ,Skin cancer ,business ,Molecular Biology ,Tyrosine kinase ,Immunodeficiency ,Biotechnology - Abstract
Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in humans, with an incidence of approximately 700,000 cases per year in the United States (Rogers et al., 2010). It is known that cSCC is strongly associated with sun exposure, specifically UVB and UVA, as well as other risk factors, such as human papillomavirus infection, immunodeficiency, and specific medications (Ratushny et al., 2012). However, the precise sequence of biological events leading to tumor development remains unknown. With projected higher incidence of patients with cSCCs in the future, there is a strong need to elucidate the molecular pathways that regulate formation of cSCCs.
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- 2018
10. Lgr6 marks epidermal stem cells with a nerve-dependent role in wound re-epithelialization
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Hyunjin Bae, Gabriella Rice, Olivia Farrelly, Paola Kuri, Yann Aubert, Stephen Prouty, Tzvete Dentchev, Brian C. Capell, Ning Li, Panteleimon Rompolas, Megan Brewster, Sixia Huang, and Wenqin Luo
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Population ,Biology ,Receptors, G-Protein-Coupled ,03 medical and health sciences ,0302 clinical medicine ,Re-Epithelialization ,Genetics ,medicine ,education ,030304 developmental biology ,Denervation ,0303 health sciences ,education.field_of_study ,integumentary system ,Epidermis (botany) ,LGR6 ,Stem Cells ,Regeneration (biology) ,Cell Biology ,Hair follicle ,Cell biology ,medicine.anatomical_structure ,Epidermal Cells ,Molecular Medicine ,Stem cell ,Wound healing ,Hair Follicle ,030217 neurology & neurosurgery - Abstract
Stem cells support lifelong maintenance of adult organs, but their specific roles during injury are poorly understood. Here we demonstrate that Lgr6 marks a regionally restricted population of epidermal stem cells that interact with nerves and specialize in wound re-epithelialization. Diphtheria toxin-mediated ablation of Lgr6 stem cells delays wound healing, and skin denervation phenocopies this effect. Using intravital imaging to capture stem cell dynamics after injury, we show that wound re-epithelialization by Lgr6 stem cells is diminished following loss of nerves. This induces recruitment of other stem cell populations, including hair follicle stem cells, which partially compensate to mediate wound closure. Single-cell lineage tracing and gene expression analysis reveal that the fate of Lgr6 stem cells is shifted toward differentiation following loss of their niche. We conclude that Lgr6 epidermal stem cells are primed for injury response and interact with nerves to regulate their fate.
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- 2021
11. 082 The immune microenvironment of cutaneous squamous cell carcinoma in situ contains suppressive phenotypes
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Stephen Prouty, Jay Patel, Thomas Vazquez, Tzvete Dentchev, and John T. Seykora
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In situ ,Cutaneous squamous cell carcinoma ,Immune microenvironment ,Cancer research ,Cell Biology ,Dermatology ,Biology ,Molecular Biology ,Biochemistry ,Phenotype - Published
- 2021
12. Whole-Exome and Transcriptome Analysis of UV-Exposed Epidermis and Carcinoma In Situ Reveals Early Drivers of Carcinogenesis
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John T. Seykora, Elizabeth A. Grice, Lily Wushanley, Qi Zheng, Hasan Bashir, Vishwas Parekh, C. O'Day, Vivian S. Lee, Cem Atillasoy, Warren S. Pear, Christopher Yeh, Stephen Prouty, Yerin Kweon, Yoko Suzuki-Horiuchi, Tzvete Dentchev, Brian C. Capell, and Eun-Hee Shim
- Subjects
0301 basic medicine ,Neoplasms, Radiation-Induced ,Skin Neoplasms ,Carcinogenesis ,Ultraviolet Rays ,RNA-Seq ,Dermatology ,Biology ,medicine.disease_cause ,Biochemistry ,Article ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Exome ,Molecular Biology ,Gene ,Exome sequencing ,Laser capture microdissection ,Receptors, Notch ,Sequence Analysis, RNA ,Gene Expression Profiling ,Cell Biology ,Genes, p53 ,Molecular biology ,genomic DNA ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Carcinoma, Squamous Cell ,Epidermis ,Carcinoma in Situ - Abstract
Squamous cell carcinoma in situ (SCCIS) is a prevalent precancerous lesion that can progress to cutaneous squamous cell carcinoma. Although SCCIS is common, its pathogenesis remains poorly understood. To better understand SCCIS development, we performed laser captured microdissection of human SCCIS and the adjacent epidermis to isolate genomic DNA and RNA for next-generation sequencing. Whole-exome sequencing identified UV-signature mutations in multiple genes, including NOTCH1–3 in the epidermis and SCCIS and oncogenic TP53 mutations in SCCIS. Gene families, including SLFN genes, contained UV/oxidative-signature disruptive epidermal mutations that manifested positive selection in SCCIS. The frequency and distribution of NOTCH and TP53 mutations indicate that NOTCH mutations may precede TP53 mutations. RNA sequencing identified 1,166 differentially expressed genes; the top five enriched gene ontology biological processes included (i) immune response, (ii) epidermal development, (iii) protein phosphorylation, (iv) regulation of catalytic activity, and (v) cytoskeletal regulation. The NEURL1 ubiquitin ligase, which targets Notch ligands for degradation, was upregulated in SCCIS. NEURL1 protein was found to be elevated in SCCIS suggesting that increased levels could represent a mechanism for downregulating Notch during UV-induced carcinogenesis. The data from DNA and RNA sequencing of epidermis and SCCIS provide insights regarding SCCIS formation.
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- 2019
13. The immune reconstitution of the skin following sex‐mismatched allogeneic haematopoietic stem cell transplant: a prospective case series utilizing fluorescence in situ hybridization and immunohistochemistry
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Sara Samimi, I. Sander, Stephen Prouty, Ellen J. Kim, Paul J. Zhang, Karolyn A. Wanat, Christine M. Cornejo, Misha Rosenbach, Robert G. Micheletti, John T. Seykora, and Campbell L. Stewart
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Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Graft vs Host Disease ,Dermatology ,Hematopoietic stem cell transplantation ,In situ hybridization ,Biology ,Article ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Immune Reconstitution ,0302 clinical medicine ,Immune system ,Transplantation Immunology ,medicine ,Humans ,Transplantation, Homologous ,Prospective Studies ,In Situ Hybridization, Fluorescence ,Skin ,medicine.diagnostic_test ,Hematopoietic Stem Cell Transplantation ,medicine.disease ,Transplantation ,Haematopoiesis ,030104 developmental biology ,Graft-versus-host disease ,Immunology ,Female ,Stem cell ,Fluorescence in situ hybridization - Abstract
Graft versus host disease (GVHD) is a common, morbid, and potentially fatal complication of allogeneic hematopoietic stem cell transplantation (aHSCT).1-3 The exact timing of the arrival of donor-derived immune cells and their profile in the skin have not been well described in humans.4-6 Fluorescent in situ hybridization (FISH) is a technique that has been used to distinguish host versus donor-derived immune cells in patients who have undergone sex-mismatched aHSCT.7 This article is protected by copyright. All rights reserved.
- Published
- 2018
14. Activating FGFR3 mutations cause mild hyperplasia in human skin, but are insufficient to drive benign or malignant skin tumors
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Todd W. Ridky, Andrew S. McNeal, Seung Ja Oh, Elizabeth K. Duperret, and Stephen Prouty
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Keratinocytes ,musculoskeletal diseases ,Seborrheic keratosis ,congenital, hereditary, and neonatal diseases and abnormalities ,Skin Neoplasms ,Stromal cell ,Carcinogenesis ,Human skin ,Oncogene Protein p21(ras) ,Biology ,medicine.disease_cause ,Mice ,Report ,medicine ,Animals ,Humans ,Receptor, Fibroblast Growth Factor, Type 3 ,Keratosis, Seborrheic ,Molecular Biology ,Cells, Cultured ,Chromosome Aberrations ,Mitogen-Activated Protein Kinase Kinases ,Hyperplasia ,Epidermis (botany) ,Infant, Newborn ,Cell Biology ,Fibroblast growth factor receptor 3 ,musculoskeletal system ,medicine.disease ,stomatognathic diseases ,Carcinoma, Squamous Cell ,Cancer research ,Heterografts ,Epidermis ,Developmental Biology - Abstract
Fibroblast growth factor receptor 3 (FGFR3) activating mutations are drivers of malignancy in several human tissues, including bladder, lung, cervix, and blood. However, in skin, these mutations are associated predominantly with benign, common epidermal growths called seborrheic keratoses (SKs). How epidermis resists FGFR3 mediated transformation is unclear, but previous studies have suggested that FGFR3 activation in skin keratinocytes may serve a tumor-suppressive role by driving differentiation and antagonizing Ras signaling. To define the role of FGFR3 in human normal and neoplastic epidermis, and to directly test the hypothesis that FGFR3 antagonizes Ras, we engineered human skin grafts in vivo with mutant active FGFR3 or shRNA FGFR3 knockdown. We show that FGFR3 active mutants drive mild hyperproliferation, but are insufficient to support benign or malignant tumorigenesis, either alone, or in combination with G 1-S checkpoint release. This suggests that additional cell-intrinsic or stromal cues are required for formation of benign SKs with FGFR3 mutations. Further, FGFR3 activation does not alter the growth kinetics or differentiation status of engineered human epidermal SCCs driven by Ras, and FGFR3 protein itself is dispensable for Ras-driven SCC. To extend these findings to patients, we examined a uniquely informative human tumor in which SCC developed in continuity with a SK, raising the hypothesis that one of the tumors evolved from the other. However, mutational analysis from each tumor indicates that the overlapping SK and SCC evolved independently and supports our conclusion that FGFR3 activation is insufficient to drive SCC.
- Published
- 2014
15. 159 Precision RNA-sequencing of squamous cell carcinoma in situ identifies therapeutic targets
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Eun-Hee Shim, John T. Seykora, Stephen Prouty, Cem Atillasoy, Qi Zheng, Vishwas Parekh, Brian C. Capell, and C. O'Day
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In situ ,Cancer research ,RNA ,Basal cell ,Cell Biology ,Dermatology ,Biology ,Molecular Biology ,Biochemistry - Published
- 2019
16. Characterization and quantification of wound-induced hair follicle neogenesis using in vivo confocal scanning laser microscopy
- Author
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Michelle Burrows, Stephen Prouty, Nikiforos Kollias, George Cotsarelis, Chengxiang Fan, and Michael A. Luedtke
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Pathology ,medicine.medical_specialty ,integumentary system ,Confocal ,Histology ,Dermatology ,Biology ,Hair follicle ,Keratin 17 ,Staining ,medicine.anatomical_structure ,Dermis ,medicine ,Wound healing ,Immunostaining - Abstract
Background: In vivo confocal scanning laser microscopy (CSLM) is a recently developed non-invasive technique for visualizing microscopic structures with the skin. CSLM has been used to characterize proliferative and inflammatory skin diseases, neoplastic skin lesions and pigmented lesions. Objective: Here, we assessed the ability of CSLM to evaluate the formation of neogenic hair follicles after a full-thickness wound in mice. Methods: Full-thickness wounds were made on the dorsal skin of 3-week-old mice. After scab detachment (SD), the number, width, length, space and volume of neogenic hair follicles were analyzed using CSLM. The results were compared with those from conventional methods, including staining for alkaline phosphatase (AP) and keratin 17 (K17) as well as histology. Results: Quantification of neogenic hair follicles using CSLM compared favorably with the results from direct measurements on isolated epidermal tissue after immunostaining for K17, a marker for the epithelial portion of new hair follicles. CSLM detected 89% of K17-stained follicles. CSLM more accurately quantified the number of new follicles compared with AP staining, which detects the dermal portion of the new follicle. The width and length measurement from CSLM and histology were very close and correlated with each other. The minimum length of a neogenic hair follicle that could be detected by CSLM was 21 μm. The space between neogenic hair follicles was decreased in histological sections compared with CSLM. Conclusion: CSLM is an accurate and valuable method for counting and measuring neogenic hair follicles non-invasively. CSLM produces images similar to histology in mice. Measurements of microstructures using CSLM more accurately reflect actual sizes as this technique avoids fixation artifacts. In vivo visualization of developing follicles with CSLM allows the detection of serial changes in hair follicle formation, thus conserving the numbers of mice required for studies and improving the detection of temporal changes in developing hair follicles.
- Published
- 2011
17. 1261 Transcriptome profiling of lentigos identifies potential therapeutic targets
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Y. Honma, C. O'Day, Y. Hayashi, Hiroshi Maeno, Stephen Prouty, and John T. Seykora
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Transcriptome profiling ,Cell Biology ,Dermatology ,Computational biology ,Biology ,Molecular Biology ,Biochemistry - Published
- 2018
18. 213 Nucleoporins are frequently mutated in SCCIS and loss of function promotes UV-induced neoplasia
- Author
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M. Pack, Christine Marshall, Xiaoshi Yang, Stephen Prouty, Hasan Bashir, John T. Seykora, P. Barriera, Hiroshi Maeno, Christopher Yeh, V. Anagnos, Qi Zheng, M. Capelson, Aaron Z. Chen, and C. O'Day
- Subjects
Chemistry ,Cell Biology ,Dermatology ,Nucleoporin ,Molecular Biology ,Biochemistry ,Loss function ,Cell biology - Published
- 2018
19. Sapienic Acid: Species-Specific Fatty Acid Metabolism of the Human Sebaceous Gland
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Apostolos Pappas and Stephen Prouty
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chemistry.chemical_classification ,Sapienic acid ,Sebaceous gland ,integumentary system ,biology ,Fatty acid metabolism ,FADS2 ,Human skin ,chemistry.chemical_compound ,Fatty acid desaturase ,medicine.anatomical_structure ,Biochemistry ,chemistry ,biology.protein ,medicine ,Polyunsaturated fatty acid ,Stearidonic acid - Abstract
Hair follicle-associated sebaceous glands secrete sebum, a highly complex lipid mixture that covers the skin surface and hair shafts. The functional versatility of lipids, combined with the wide array of sebaceous lipid classes and aliphatic moieties, provide mammals with a substrate that facilitates adaptation to their diverse environments, including interaction with animals and microbes. Unique among the complexity of sebaceous lipids is sapienic acid, a 16 carbon monounsaturated fatty acid with an extremely rare position of the double bond, located between carbons 6 and 7 from the carboxyl terminal. Human sebum is the only documented location in the animal kingdom where sapienic acid is abundant and naturally occurring. It is produced by fatty acid desaturase 2 (FADS2), the same enzyme that is rate-limiting in the formation of polyunsaturated fatty acids. Multiple tissue-specific mechanisms are utilized in the human sebaceous gland in order to “repurpose” FADS2 for the production of sapienic acid, chief among which is the reduction of competing desaturase activity. Among mammals, human sebum has the highest amount of free fatty acids, of which sapienic acid is the most abundant monounsaturated fatty acid. Consistent with the role of fatty acids in modulating host-microbe interactions, sapienic acid has the highest antimicrobial activity among free fatty acids in human sebum, while also demonstrating selectivity for Staphylococcus aureus, an opportunistic pathogen. Increased infection by Staphylococcus aureus is associated with a reduction in sapienic acid in sebum of patients with atopic dermatitis, and topical application of sapienic acid is correlated with decreased bacterial load and amelioration of symptoms. Taken together, this strongly suggests that sapienic acid functions as a “first-line” component of the innate immune system at the cutaneous surface. The species-specific nature of sapienic acid in human sebum is related to the unique architecture of human skin and its microbial environment. Insight into pathogenesis of human skin disease will benefit from further investigation into the biochemistry of sapienic acid production in human sebaceous glands.
- Published
- 2014
20. 127 UV-signature mutations in the nuclear pore complex are elevated in squamous cell carcinoma in situ and adjacent epidermis
- Author
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Aaron Z. Chen, Elizabeth A. Grice, M. Capelson, John T. Seykora, M. Pack, V. Anagnos, Hasan Bashir, Stephen Prouty, P. Barriera, and Qi Zheng
- Subjects
In situ ,Epidermis (botany) ,Chemistry ,Basal cell ,Cell Biology ,Dermatology ,Anatomy ,Nuclear pore ,Molecular Biology ,Biochemistry ,Cell biology - Published
- 2017
21. 112 UV-signature Notch mutations are subclonal in human UV-exposed skin and clonal in squamous cell carcinoma in situ
- Author
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Z. Qi, P. Barriera, V. Anagnos, Stephen Prouty, R. Tang, John T. Seykora, Aaron Z. Chen, L. Lawton, and Hasan Bashir
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In situ ,Chemistry ,Cancer research ,Basal cell ,Cell Biology ,Dermatology ,Molecular Biology ,Biochemistry - Published
- 2016
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