Dermal Cell News Volume 3.35 | Oct 23 2017

TOP STORY

Inflammation Trains the Skin to Heal Faster

Scars may fade, but the skin remembers. Scientists reveal that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, teaching them to heal subsequent injuries faster. [Press release from Rockefeller University discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

A Protein Phosphatase Network Controls the Temporal and Spatial Dynamics of Differentiation Commitment in Human Epidermis

Epidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation. The transition between the two cell states, termed commitment, is poorly understood. Investigators characterized commitment by integrating transcriptomic and proteomic data from disaggregated primary human keratinocytes held in suspension to induce differentiation. [Elife] Abstract

Repigmentation of Human Vitiligo Skin by NBUVB is Controlled by Transcription of GLI1 and Activation of β-Catenin Pathway in the Hair Follicle Bulge Stem Cells

The authors developed an application that combined laser capture microdissection and subsequent whole transcriptome RNA sequencing of hair follicle bulge melanocyte precursors, and compared their gene signature to that of regenerated mature epidermal melanocytes from the narrow band UVB (NBUVB)-treated vitiligo skin. [J Investig Dermatol] Abstract

Androgens Trigger Different Growth Responses in Genetically Identical Human Hair Follicles in Organ Culture That Reflect Their Epigenetic Diversity in Life

Researchers used hair follicles to establish an androgen-responsive human organ culture model. They showed that women’s intermediate facial follicles respond to men’s higher androgen levels by synthesizing more hair over several days, unlike donor-matched, androgen-insensitive, terminal follicles. They demonstrated that androgen receptors-androgen-activated gene transcription regulators-are required and are present in vivo within these follicles. [FASEB J] Abstract

Transcription Factors and Stress Response Gene Alterations in Human Keratinocytes Following Solar Simulated Ultra Violet Radiation

Investigators report global changes in gene expression as well as associated pathways and upstream transcription factors in human keratinocytes exposed to solar-simulated ultraviolet radiation (ssUVR). Human HaCaT keratinocytes were exposed to either a single dose or 5 repetitive doses of ssUVR. [Sci Rep] Full Article

Exosomes Secreted by Human Adipose Mesenchymal Stem Cells Promote Scarless Cutaneous Repair by Regulating Extracellular Matrix Remodeling

Scientists found that intravenous injection of human adipose mesenchymal stem cells (ASC-Exos) decreased the size of scars and increased the ratio of collagen III to collagen I in murine incisional wounds. Exosome treatment also prevented the differentiation of fibroblasts into myofibroblasts and increased the ratio of transforming growth factor-β3 (TGF-β3) to TGF-β1 in vivo. [Sci Rep] Full Article

SKIN CANCERS & DISORDERS

Crystallinity of Double-Stranded RNA-Antimicrobial Peptide Complexes Modulates Toll-Like Receptor 3-Mediated Inflammation

Double-stranded RNA (dsRNA) induces production of pro-inflammatory cytokines in normal human epidermal keratinocytes (NHEK) by specific binding to endosomal Toll-like receptor-3 (TLR3). It has been shown that hyperactivation of TLR3 in psoriatic keratinocytes by dsRNA can occur in the presence of human antimicrobial peptide LL37. Scientists combined synchrotron X-ray scattering, microscopy, computer simulations, and measurements of NHEK cytokine production to elucidate a previously unanticipated form of specific molecular pattern recognition. [ACS Nano] Abstract | Graphical Abstract

MNK1/2 Inhibition Limits Oncogenicity and Metastasis of KIT-Mutant Melanoma

Researchers determined that C-KIT stimulates MAP kinase–interacting serine/threonine kinases 1 and 2 (MNK1/2), which phosphorylate eukaryotic translation initiation factor 4E and render it oncogenic. Depletion of MNK1/2 in melanoma cells with oncogenic C-KIT inhibited cell migration and mRNA translation of the transcriptional repressor SNAI1 and the cell cycle gene CCNE1. [J Clin Invest] Full Article

Wild-Type KRAS Is a Novel Therapeutic Target for Melanoma Contributing to Primary and Acquired Resistance to BRAF Inhibition

Scientists identified wild-type Kirsten Rat sarcoma (KRAS) as a novel therapeutic target in melanoma. KRAS inhibition functioned synergistically with BRAF inhibition to reduce melanoma proliferation and to induce apoptosis independently of BRAF mutational status. [Oncogene] Abstract

Suppression of RAC1-Driven Malignant Melanoma by Group a PAK Inhibitors

The authors explored the effects of p21-activated kinase (PAK) inhibition on RAC1^P29S signaling in zebrafish embryonic development, in the proliferation, survival and motility of RAC1^P29S-mutant human melanoma cells, and on tumor formation and progression from such cells in mice. [Oncogene] Abstract

ALK Inhibitor Response in Melanomas Expressing EML4-ALK Fusions and Alternate ALK Isoforms

The authors demonstrated that ALK fusions occur in malignant melanomas and respond to targeted therapy whereas melanomas expressing ALKATI do not respond to ALK inhibitors. [Mol Cancer Ther] Abstract

Photodynamic Therapy Inhibits Melanogenesis through Paracrine Effects by Keratinocytes and Fibroblasts

The authors investigated the mechanism underlying the whitening effects of photodynamic therapy (PDT) on melanocytes in vitro and in vivo. Exposure of melanocytes to PDT in vitro reduced their melanin content and tyrosinase activity without, however, affecting cell survival. [Mol Cancer Ther] Abstract

Aquaporin-1 Inhibition Reduces Metastatic Formation in a Mouse Model of Melanoma

The authors tested the hypothesis that aquaporin-1 inhibition affects animal survival and lung nodule formation. Melanoma was induced by injecting B16F10 cells into the back of C57BL6J mice. [J Cell Mol Med] Full Article

Stem Cells as Potential Candidates for Psoriasis Cell-Replacement Therapy

The effect of stem cells in the epidermis and stem cells on T cells has been identified and the dysfunction of various types of stem cells may be a prime cause of dysregulation of the inflammatory response in psoriasis. However, exploring these mechanisms in detail could provide a chance to develop new therapeutic strategies. The authors reviewed data on the role played by stem cells in the pathogenesis of psoriasis and initial attempts at using them in treatment. [Int J Mol Sci] Full Article

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

OncoSec Presents Positive Phase II Data for ImmunoPulse^® IL-12 in Combination with Pembrolizumab Demonstrating a Best Overall Response Rate (BORR) of 50% in Predicted Anti-PD-1 Non-Responder Melanoma Patients

OncoSec Medical Inc. announced updated Phase II clinical and immune monitoring data from patients treated with its investigational therapy, ImmunoPulse^® IL-12 as a monotherapy versus the combination of ImmunoPulse IL-12 and the approved anti-PD-1 therapy pembrolizumab. [Press release from OncoSec Medical Inc. discussing research presented at the 2017 9th World Congress of Melanoma, Brisbane] Press Release

AOBiome Therapeutics Reports Positive Efficacy Results from Phase IIb Clinical Trial of Ammonia Oxidizing Bacteria (AOB) for the Treatment of Acne Vulgaris

AOBiome Therapeutics announced positive efficacy and safety findings from the Phase IIb clinical trial of the Company’s AOB product candidate for the treatment of mild-to-moderate acne vulgaris. [AOBiome Therapeutics] Press Release

U.S. Food and Drug Administration (FDA) Accepts Bristol-Myers Squibb’s Application for Opdivo (Nivolumab) in Patients with Resected High-Risk Advanced Melanoma and Grants Priority Review

Bristol-Myers Squibb Company announced that the FDA has accepted for priority review its supplemental Biologics License Application for Opdivo to treat patients with melanoma who are at high risk of disease recurrence following complete surgical resection. [Bristol-Myers Squibb Company] Press Release

Iranian Scholar Sentenced to Death

A judge in Tehran has ordered the death penalty for Iranian researcher Ahmadreza Djalali, according to his wife and diplomatic sources in Italy. Djalali is affiliated with the Karolinska Institute in Stockholm, Sweden, and the University of Eastern Piedmont in Novara, Italy. A resident of Sweden with his family, Djalali was arrested in April 2016 on an academic visit to Tehran and accused of “collaboration with a hostile government”. He works on improving hospitals’ emergency responses to armed terrorism and radiological, chemical and biological threats. [Nature News] Editorial

In Brazil, Researchers Struggle to Fend Off Deepening Budget Cuts

With time and money running out, Brazilian scientists are turning up the pressure on the federal government to avoid a total collapse of the national science and technology funding system before the end of the year. Researchers delivered a petition with more than 82,000 signatures to congressional leaders in Brasília, demanding the reversal of deep budget cuts that have left research institutions struggling to pay even basic water and electricity bills. [ScienceInsider] Editorial

Rand Paul Takes a Poke at U.S. Peer Review Panels

Senate Republicans have launched a new attack on peer review by proposing changes to how the U.S. government funds basic research. [ScienceInsider] Editorial

NEW European CanCer Organization (ECCO) 2018: European Cancer Summit
September 7-9, 2018
Vienna, Austria

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

NEW Assistant or Associate Professor – Melanoma (MD Anderson Cancer Center)

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 Position – Wound Healing (University of Connecticut Health Center)

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

PhD Position – Molecular Biology (University of Luxembourg)

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

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