Dermal Cell News Volume 3.34 | Oct 16 2017

TOP STORY

Cancer Drug Addiction Is Relayed by an ERK2-Dependent Phenotype Switch

Scientists performed an unbiased CRISPR–Cas9 knockout screen on melanoma cells that were both resistant and addicted to inhibition of the serine/threonine-protein kinase BRAF, in order to functionally mine their genome for ‘addiction genes’. [Nature] Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Stem Cell Secretome and Its Effect on Cellular Mechanism Relevant to Wound Healing

In vitro studies demonstrated that the secretome activates the PI3K/Akt or FAK/ERK1/2 signaling cascades and subsequently enhances the proliferative and migratory abilities of various types of skin cells such as fibroblasts, keratinocytes, and vascular epithelial cells, ultimately accelerating wound contraction. [Mol Ther] Abstract

Engineering Fibrin Hydrogels to Promote the Wound Healing Potential of Mesenchymal Stem Cell Spheroids

To capitalize on the therapeutic potential of spheroids, the authors engineered a fibrin gel delivery vehicle to simultaneously enhance the proangiogenic and anti-inflammatory potential of entrapped human mesenchymal stem cells spheroids. [Acta Biomater] Abstract | Graphical Abstract

Fibrinogen-Modified Sodium Alginate as a Scaffold Material for Skin Tissue Engineering

Researchers found that thrombin-modified alginate sponges can be successfully used as a grafting material by itself to promote skin healing and regeneration and also as a scaffold for 3D bioequivalent construction. [Biomed Mater] Abstract

Fibromodulin Reduces Scar Formation in Adult Cutaneous Wounds by Eliciting a Fetal-Like Phenotype

Investigators showed that fibromodulin significantly reduces scar formation while simultaneously increasing scar strength in both adult rodent models and porcine wounds, which simulate human cutaneous scar repair. [Signal Transduct Target Ther] Full Article

SKIN CANCERS & DISORDERS

Mouse Cutaneous Melanoma Induced by Mutant BRaf Arises from Expansion and Dedifferentiation of Mature Pigmented Melanocytes

To identify the cells at the origin of melanoma, scientists combined single-cell lineage-tracing and transcriptomics approaches with time-lapse imaging. A mouse model that recapitulates key histopathological features of human melanomagenesis was created by inducing a BRafV600E-driven melanomagenic program in tail interfollicular melanocytes. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

Melanocyte Stem Cell Activation and Translocation Initiate Cutaneous Melanoma in Response to UV Exposure

Investigators employed mouse models to define the role of melanocyte stem cells (MCSCs) as melanoma cells of origin, demonstrated that MCSC quiescence acts as a tumor suppressor, and identified the extrinsic environmental and molecular factors required for the critical early steps of melanoma initiation. [Cell Stem Cell] Full Article | Graphical Abstract

A Non-Coding Function of TYRP1 mRNA Promotes Melanoma Growth

Researchers report that TYRP1 mRNA, in addition to encoding tyrosinase-related protein 1 (TYRP1), indirectly promotes cell proliferation by sequestering miR-16 on non-canonical miRNA response elements. The sequestered miR-16 is no longer able to repress its mRNA targets, such as RAB17, which is involved in melanoma cell proliferation and tumour growth. [Nat Cell Biol] Abstract

An Analysis of IL-36 Signature Genes and Individuals with IL1RL2 Knockout Mutations Validates IL-36 as a Psoriasis Therapeutic Target

Investigators defined the genes that are induced by interleukin (IL)-36 cytokines in primary human keratinocytes. They demonstrated a significant IL-36 signature among the transcripts that are up-regulated in plaque psoriasis and the susceptibility loci associated with the disease in genome-wide studies. [Sci Transl Med] Abstract

Programmed Cell Death Protein Ligand-1 Silencing with Polyethylenimine–Dermatan Sulfate Complex for Dual Inhibition of Melanoma Growth

The authors hypothesized that siRNA targeting protein ligand-1 (siPD-L1) will suppress melanoma growth, acting on both immune checkpoint and intrinsic tumorigenesis pathways. They tested this hypothesis by delivering siPD-L1 with a polymeric carrier consisting of disulfide-cross-linked polyethylenimine and dermatan sulfate, which they previously found to have a specific interaction with CD146-positive B16F10 melanoma cells. [ACS Nano] Abstract | Graphical Abstract

Super-Enhancers Define a Proliferative PGC-1α-Expressing Melanoma Subgroup Sensitive to BET Inhib

Researchers provided evidence that melanoma models with elevated PGC-1α levels are characteristic of the proliferative phenotype and are sensitive to bromodomain and extra-terminal domain (BET) inhibitor treatment. A super-enhancer region highly occupied by the BET family member BRD4 was identified for the PGC-1α gene. [Oncogene] Full Article

Vitiligo Skin: Exploring the Dermal Compartment

Scientists reveal within the dermal compartment cells with a myofibroblast phenotype and a predisposition to premature senescence, indicating the existence of altered cross-talk between dermal and epidermal components which may affect melanocyte functionality even in the apparently normal skin of vitiligo patients. [J Invest Dermatol] Full Article

Progress in Development of Bioderived Materials for Dermal Wound Healing

The authors describe the recent developments made in the processing of bioderived materials employed for cutaneous wound healing, including newly developed materials such as keratin and soy protein. They focused on the key properties of the bioderived materials that have shown great promise in improving wound healing, restoration and reconstruction. [Regen Biomater] Full Article

Visit our reviews page to see a complete list of reviews in the dermal cell research field.

Ortho Dermatologics Announces Two-Year Findings from Pivotal Phase III Study of SILIQ^™ (Brodalumab) Injection Data Demonstrating Long-Term Efficacy Profile

Ortho Dermatologics announced results from the Pivotal Phase III long-term extension study, which demonstrated that SILIQ^™ injection provided sustained high levels of skin clearance over more than two years in patients with moderate-to-severe psoriasis. [Press release from Ortho Dermatologics discussing research presented at 2017 Fall Clinical Dermatology Conference, Las Vegas] Press Release

Janssen Announces U.S. FDA Approval of Stelara^® (Ustekinumab) for the Treatment of Adolescents with Moderate-to-Sever Plaque Psoriasis

Janssen Biotech, Inc. announced that the FDA has approved an expanded indication for STELARA^® for the treatment of adolescents with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. [Janssen Biotech, Inc.] Press Release

U.S. FDA Approves New Continued Access Protocol for the ReCell^® Device for Treatment of Burn Injuries

Avita Medical announced that the FDA has approved a supplement to the Company’s Investigational Device Exemption for its ReCell^® Autologous Cell Harvesting Device. [Avita Medical] Press Release

MC2 Therapeutics A/S Announces First Patient Dosed in Pivotal US Phase III Trial in Psoriasis Vulgaris

MC2 Therapeutics A/S announced that first patient has been dosed in its pivotal Phase III clinical trial assessing the safety and efficacy of MC2-01 Cream compared to MC2-01 vehicle and an active comparator for the treatment of plaque psoriasis in adult patients. [MC2 Therapeutics A/S] Press Release

OncoSec Initiates Registration Directed Clinical Trial, KEYNOTE-695, of ImmunoPulse^® IL-12 in Combination with Merck’s KEYTRUDA^® (Pembrolizumab)

OncoSec Medical Inc. announced that it has initiated its Phase IIb registration directed trial. The study is a global, multicenter Phase IIb trial of OncoSec’s investigational therapy, ImmunoPulse^® IL-12, combined with KEYTRUDA^®, an anti-PD-1 therapy marketed by Merck, in patients with unresectable metastatic melanoma who have progressed or are progressing on an anti-PD-1 therapy. [OncoSec Medical Inc.] Press Release

FDA Advisers Back Gene Therapy for Rare Form of Blindness

Advisers to the FDA have paved the way for the agency’s first approval of a gene therapy to treat a disease caused by a genetic mutation. A panel of external experts unanimously voted that the benefits of the therapy, which treats a form of hereditary blindness, outweigh its risks. [Nature News] Editorial

German Researchers Resign from Elsevier Journals in Push for Nationwide Open Access

Five leading German scientists have resigned from their editorial positions at journals published by Elsevier, the latest step in a battle over open-access and subscription policies between the Dutch publishing giant and a consortium of German libraries, universities, and research institutes. [ScienceInsider] Editorial

NEW 17^th World Congress on Cancers of the Skin 2018
August 15-18, 2018
Sydney, Australia

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

NEW Faculty Positions – Cancer Research (Huntsman Cancer Institute)

Postdoctoral Position – Melanoma (The Danish Cancer Society Research Center)

Postdoctoral Fellow – Cancer Genomics (University of California, San Diego)

Senior Scientist – Cancer Biology (Dana Farber Cancer Center)

Postdoctoral Fellowship – Cancer Development (Lund University)

Postdoctoral Position – Wound Healing (University of Connecticut Health Center)

Postdoctoral Fellow – Molecular Oncology and Mouse Modeling (Moffitt Cancer Center)

Postdoctoral Positions – PD-L1/PD-1 Signals in Melanoma (University of Texas Health Science Center at San Antonio)

PhD Position – Molecular Biology (University of Luxembourg)

Research Fellow – Melanoma (Dana-Farber Cancer Institute)

Research Technician – Adult Skin Stem Cells (Howard Hughes Medical Institute)

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