Dermal Cell News Volume 5.12 | Apr 8 2019

TOP STORY

Stem Cell Competition Orchestrates Skin Homeostasis and Aging

Scientists report that the expression of the hemidesmosome component collagen XVII (COL17A1) by epidermal stem cells fluctuated physiologically through genomic/oxidative stress-induced proteolysis, and that the resulting differential expression of COL17A1 in individual stem cells generated a driving force for cell competition. [Nature] Abstract | Editorial

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Hemidesmosomes and Focal Adhesions Treadmill as Separate but Linked Entities during Keratinocyte Migration

Examining migrating human primary human keratinocytes the authors found that hemidesmosomes clustered as ordered arrays consisting of multiple chevrons that were flanked by actin-associated focal adhesions. These hemidesmosomal arrays with intercalated focal adhesions extended from the cell rear to the cell front. [J Invest Dermatol] Abstract

Immune Tolerance of Tissue-Engineered Skin Produced with Allogeneic or Xenogeneic Fibroblasts and Syngeneic Keratinocytes Grafted on Mice

To evaluate graft tolerance of engineered-tissues containing non-autologous fibroblasts, tissue-engineered skin substitutes produced with syngeneic, allogeneic or xenogeneic fibroblasts associated with syngeneic, allogeneic or xenogeneic epithelial cells were grafted in mice as primary and secondary grafts. [Acta Biomater] Abstract | Graphical Abstract

The Ciliary GTPase Arl3 Maintains Tissue Architecture by Directing Planar Spindle Orientation during Epidermal Morphogenesis

Researchers demonstrated that ciliary GTPase Arl3 was required for mitotic spindle orientation of basal stem cells during skin development. Arl3 loss diminished cell divisions within the plane of the epithelium, leading to increased perpendicular divisions, expansion of progenitor cells, and loss of epithelial integrity. [Development] Abstract

Studies on Differentiation-Dependent Expression and Activity of Distinct Transglutaminases by Specific Substrate Peptides Using Three Dimensional Reconstituted Epidermis

Using isozyme-specific substrate peptides that enable detection of transglutaminase (TG) activity, the authors investigated the expression and the activation pattern of each isozyme during differentiation in this culture system. In the differentiating cells, the protein levels, enzymatic activities, as well as localization of TG1 and TG3 exhibited distinct patterns. [FEBS J] Abstract

Keratin Scaffolds with Human Adipose Stem Cells: Physical and Biological Effects toward Wound Healing

Keratin scaffolds supported human adipose stem cells (hASCs) adhesion, proliferation and differentiation. In vivo study performed on ICR mice showed that keratin scaffolds with hASCs shortened skin wound healing time, accelerated epithelialization and promoted wound remodeling. [J Tissue Eng Regen Med] Abstract

SKIN CANCERS & DISORDERS

Regorafenib Promotes Anti-Tumor Immunity via Inhibiting PD-L1 and IDO1 Expression in Melanoma

Investigators showed that regorafenib, in vitro and in vivo, strongly promoted anti-tumor efficacy when combined with IFN-γ or immune checkpoint blockade. By targeting the RET-Src axis, regorafenib potently inhibited JAK1/2-STAT1 and MAPK signaling and subsequently attenuated IFN-γ induced PD-L1 and IDO1 expression without much affecting MHC-I expression. [Clin Cancer Res] Abstract

Accumulation of Circulating CCR7⁺ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway

CCR7 expression and CCL19 secretion were observed in melanoma cell lines. The CCR7⁺ melanoma cell subpopulation co-expressed PD-L1 and galectin-9 and had stemness properties. Analysis of melanoma-derived cancer stem cells (CSCs) showed high CCR7 expression; these CSCs were efficiently recognized and killed by NK cells. [Cancer Immunol Res] Abstract

Intracellular Notch1 Signaling in Cancer-Associated Fibroblasts Dictates the Plasticity and Stemness of Melanoma Stem/Initiating Cells

Using mesenchymal stem cell-derived fibroblasts (MSC-DF) harboring reciprocal loss- and gain-of-function Notch1 signaling, scientists found that MSC-DF^Notch1-/- prompted co-cultured melanoma cells to form more spheroids and acquire the phenotype of melanoma stem/initiating cells (MICs), whereas MSC-DF^N1IC+/+ suppressed melanoma cell sphere formation and mitigated the properties of the MICs. [Stem Cells] Abstract

Interleukin 32 Expression in Human Melanoma

Researchers evaluated the impact of proinflammatory molecules TNFα and IFNγ on interleukin 32 (IL32) expression and dedifferentiation in melanoma cell lines in vitro. In order to study the transcriptional regulation of IL32 in these cell lines, they cloned up to 10.5 kb of the 5′ upstream region of the human IL32 gene into a luciferase reporter vector. [J Transl Med] Full Article

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Models of Human Psoriasis: Zebrafish the Newly Appointed Player

The authors briefly overview psoriasis and revise in a digested fashion the preclinical research models available, emphasizing the zebrafish as a powerful tool in the study of immune effectors on the same, and how it supports the discovering of new therapies that may help in controlling this widespread disease around the globe. [Dev Comp Immunol] Abstract

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AVITA Medical Announces Presentation Highlighting Results of Study Using RECELL^® System to Treat Third-Degree Burns in Pediatric Patients

AVITA Medical announced that interim results describing clinical outcomes for pediatric patients treated using the RECELL^® System were presented. [Press release from AVITA Medical discussing research presented at the American Burn Association (ABA) 51^st Annual Meeting, Las Vegas] Press Release

Genocea Presents Data Supporting Utility of ATLAS™ Platform in Predicting Melanoma Patient Response to Immune Checkpoint Inhibitors

Genocea Biosciences, Inc. announced the presentation of data from ATLAS™, its ex vivo platform for comprehensively profiling patients’ antigen-specific T cells responses. [Press release from Genocea Biosciences, Inc. discussing research presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR), Atlanta] Press Release

Is Your Melanoma Hot Enough for Immunotherapy?

A University of Colorado Cancer Center study identified a possible way to predict which melanomas are hot and cold: Tumors with mutations in genes leading to over-activation of the NF-kB signaling pathway were more than three times as likely to respond to anti-PD1 immunotherapy compared with tumors in which these changes were absent. [Press release from University of Colorado Cancer Center discussing research presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR), Atlanta] Press Release

Azitra Demonstrates Feasibility of Engineering the Skin Microbiome to Treat Serious Skin Conditions

Researchers from Azitra, Inc., in collaboration with independent, nonprofit biomedical research institution The Jackson Laboratory, have demonstrated the feasibility of engineering a commensal bacterium to deliver a key therapeutic protein to the skin. [Press release from Azitra, Inc. discussing research to be presented at the Keystone Symposia on Skin Health and Disease, Hannover] Press Release

Iovance Biotherapeutics Announces First Patient Dosed in Cohort 4 of Pivotal InnovaTIL-01 Study of Lifileucel in Metastatic Melanoma

Iovance Biotherapeutics, Inc. announced that first patient has been dosed in Cohort 4, the pivotal cohort of the innovaTIL-01 study of lifileucel. Cohort 4 is designed to enroll 75 patients with advanced melanoma. [Iovance Biotherapeutics, Inc.] Press Release

Novartis First-in-Class Cosentyx^® Approved in China for Psoriasis Patients

Novartis announced that the China Health Authority NMPA approved Cosentyx^®, the first-in-class interleukin-17A inhibitor for moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. [Novartis AG] Press Release

Encore Dermatology Inc. Acquires SERNIVO^®, TRIANEX^® and PROMISEB^®

Encore Dermatology Inc. announced that it has acquired rights for SERNIVO^® Spray, 0.05%, as well as rights to market and distribute TRIANEX^® 0.05% and PROMISEB^® Topical Cream in the United States from Dr. Reddy’s Laboratories Ltd., through its wholly owned subsidiary Promius Pharma LLC. [Encore Dermatology Inc.] Press Release

OncoSec Announces Advanced Therapy Medicinal Product Classification From the EMA for TAVO™ in Refractory Metastatic Melanoma

OncoSec Medical Incorporated announced that it has received Advanced Therapy Medicinal Product classification for the company’s lead investigational product candidate, TAVO™, as a potential treatment for refractory metastatic melanoma from the European Medicines Agency (EMA). [OncoSec Medical Incorporated] Press Release

XenoTherapeutics Wins ABA’s Best Bioengineering Paper Award for Research on Xeno-Skin™, a Novel Xenotransplantation Treatment for Severe Burns

XenoTherapeutics, Inc. received the Burke/Yannas Award for Best Bioengineering Paper at the 51^st conference of the American Burn Association (ABA) for its research of Xeno-Skin™. Xeno-Skin is a first-of-its-kind xenotransplantation product, designed to provide a safe temporary coverage mechanism for patients with severe burn wounds. [XenoTherapeutics, Inc. (Business Wire, Inc.)] Press Release

AIM at Melanoma Opens First Melanoma Tissue Bank in the US

AIM at Melanoma announced the grand opening of the first branch of the International Melanoma Tissue Bank Consortium at the University of Pittsburgh Medical Center, Hillman Cancer Center. The Pittsburgh site is one of six global locations of the consortium. [AIM at Melanoma (PR Newswire Association LLC.)] Press Release

Brazil’s Government Freezes Nearly Half of Its Science Spending

Researchers in Brazil are up in arms after President Jair Bolsonaro’s government announced late March that it had frozen 42% of the budget for the country’s science and communications ministry. [Nature News] Editorial

FDA, New York Attorney General Go After Stem Cell Clinics

On April 3, the FDA sent letters to 20 companies providing stem cell treatments, reports The New York Times, reminding them that they may require FDA approval and should take action to comply. The agency also issued a warning to a stem cell company for violating good manufacturing practices. [The Scientist] Editorial

NEW Gordon Research Seminar: Biomaterials and Tissue Engineering
July 28-August 2, 2019
Barcelona, Spain

Visit our events page to see a complete list of events in the community.

NEW Research Assistant II – Melanoma Medical Oncology (MD Anderson Cancer Center)

Postdoctoral Fellowship – Epidermal Stem Cell Research (UC San Diego)

Postdoctoral Researcher – Immune-Epidermal Cell Stress Response (Queen Mary University of London)

Postdoctoral Fellowship – Immune Cell-Mediated Regulation (Hospital for Special Surgery)

Junior Faculty and Postdoctoral Positions – Epigenetic Regulation (Henry Ford Health System)

Postdoctoral Researcher – Skin Biology (University of Wisconsin-Madison)

Director – Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health)

Postdoctoral Scientist – Molecular Oncology (University of Manchester)

Research Assistant – Burn Research (Sunnybrook Health Sciences Centre)

Postdoctoral Fellowship – Tumor Immunology and Cancer Metabolism (Roswell Park Comprehensive Cancer Center)

PhD Position – Epidermal Tissue Mechanics (Forschungszentrum Jülich)

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