Dermal Cell News Volume 4.27 | Aug 13 2018

TOP STORY

Central Role of Autophagic UVRAG in Melanogenesis and the Suntan Response

Absence of UVRAG dispersed biogenesis of lysosome-related organelles complex 1 distribution and activity, resulting in impaired melanogenesis in vitro and defective melanocyte development in zebrafish in vivo. [Proc Natl Acad Sci USA] Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Genome Editing of Human Primary Keratinocytes by CRISPR/Cas9 Reveals an Essential Role of the NLRP1 Inflammasome in UVB Sensing

Scientists established a protocol that allowed the generation of CRISPR/Cas9-targeted human primary keratinocytes. Their experiments revealed an essential role of the NLRP1 rather than the NLRP3 inflammasome in UVB sensing and subsequent IL-1β and -18 secretion by keratinocytes. [J Invest Dermatol] Abstract

Plasminogen Activator Inhibitor-1 and Tenascin-C Secreted by Equine Mesenchymal Stromal Cells Stimulate Dermal Fibroblast Migration In Vitro and Contribute to Wound Healing In Vivo

Investigators found that mesenchymal stromal cell-derived plasminogen activator inhibitor-1 and tenascin-C significantly increased dermal fibroblast migration in vitro and improved wound healing in vivo by decreasing time to wound closure. [Cytotherapy] Abstract

SKIN CANCERS & DISORDERS

Peptide-Modified Vemurafenib-Loaded Liposomes for Targeted Inhibition of Melanoma via the Skin

Transdermal delivery of peptide-modified vemurafenib-loaded liposomes (Vem-TD-Lip) effectively targeted and inhibited subcutaneous melanoma in male mice, the administration of Vem-TD-Lip through skin was better than that through oral administration and intravenous injection in terms of reducing damage to major organs and enhancing antitumor efficacy, and the peptide TD significantly enhanced the delivery of Vem-TD-Lip across the skin. [Biomaterials] Abstract | Graphical Abstract

CRISPR/Cas9-Mediated In Situ Correction of LAMB3 Gene in Keratinocytes Derived from Junctional Epidermolysis Bullosa Patient

Researchers reported the first application of CRISPR/Cas9-mediated homology direct repair to in situ restore LAMB3 expression in junctional epidermolysis bullosa keratinocytes in vitro and in immunodeficient mice transplanted with genetically corrected skin equivalents. Monoallelic-targeted integration of LAMB3 cDNA was sufficient to in vitro recapitulate the adhesive property, the colony formation typical of normal keratinocytes, as well as their cell growth. [Mol Ther] Abstract

MicroRNA-211 Loss Promotes Metabolic Vulnerability and BRAF Inhibitor Sensitivity in Melanoma

Scientists generated miR-211 loss-of-function cell lines using CRISPR/Cas9 technology and showed that miR-211 loss slowed growth and invasion in vitro, inhibited phosphoinositol-3-kinase signaling, and inhibited melanoma growth in vivo. miR-211 was upregulated by the BRAF inhibitor vemurafenib and in vemurafenib-resistant melanoma cells, with miR-211 loss rendering them more drug sensitive. [J Invest Dermatol] Abstract

Glutathione Reductase-Mediated Thiol Oxidative Stress Suppresses Metastasis of Murine Melanoma Cells

The authors demonstrated that glutathione reductase (GR) inhibition generated oxidative stress and suppresses lung metastasis and subcutaneous growth of melanoma in vivo. Inhibitory effects by GR activity reduction were observed on cell proliferation, colony formation, cell adhesion, migration and invasion in melanoma cells in vitro. [Free Radic Biol Med] Full Article | Graphical Abstract

Polycystin-1 Downregulation Induces ERK-Dependent mTOR Pathway Activation in a Cellular Model of Psoriasis

Investigators showed that polycystin-1 (PC1) knockdown in HaCaT cells led to an elevated mRNA expression of psoriasis-related biomarkers Ki-67, IL-6, TNF-α, VEGF and Bcl-2, while PC1 functional inhibition was accompanied by increased cell proliferation and migration of HaCaT cells. PC1 knockdown via siRNA in HaCaT cells was followed by activation of critical molecules of the mTOR and MAPK pathways and this mTOR pathway activation was ERK-dependent. [Biochim Biophys Acta] Abstract

Isoliquiritigenin Suppresses Human Melanoma Growth by Targeting miR-301b/LRIG1 Signaling

The suppressive effect of isoliquiritigenin on cell growth was reversed by ectopic expression of miR-301b. Bioinformatic analysis showed that miR-301b may target leucine rich repeats and immunoglobulin like domains 1 (LRIG1), miR-301b suppressed the luciferase activity of reporter constructs containing 3’UTR of LRIG1 as well as the expression level of LRIG1. [J Exp Clin Cancer Res] Full Article

Gomesin Inhibits Melanoma Growth by Manipulating Key Signaling Cascades that Control Cell Death and Proliferation

Gomesin and gomesin-like homolog (HiGom) compromised proliferation of melanoma cells via activation of the p53/p21 cell cycle check-point axis and the Hippo signaling cascade, together with attenuation of the MAP kinase pathway. Both gomesin peptides exhibited antitumoral activity in melanoma AVATAR-zebrafish xenograft tumors and HiGom also reduced tumor progression in a melanoma xenograft mouse model. [Sci Rep] Full Article

Locally Targeting the IL-17/ IL-17RA Axis Reduced Tumor Growth in a Murine B16F10 Melanoma Model

Knockdown of IL-17RA led to a significantly decreased capability of B16F10 cells to form tumors in vivo, similar to that in IL-17- deficient mice. Local application of adenovirus delivering a shRNA against IL-17RA not only significantly suppressed tumor development, but also enhanced anti-tumor immunity by increasing the IFNγ-expressing T cells and not Treg cells. [Hum Gene Ther] Abstract

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Matrix Molecules and Skin Biology

The authors present the composition and features of the skin extracellular matrix (ECM) during homeostasis and regeneration. They discuss genetic and acquired ECM diseases affecting skin, and provide a short outlook to therapeutic strategies for them. [Semin Cell Dev Biol] Abstract

Keratins and Epidermolysis Bullosa Simplex

Scientists summarize the various aspects of the presence of keratins 5 and 14 in the epidermis, their relation to the incidence and severity of epidermolysis bullosa simplex phenotypes, and the processes with which these proteins can affect them. [J Cell Physiol] Abstract

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

OncoSec Enters Research Collaboration Agreement with UCLA and Roger S. Lo, M.D., Ph.D.

OncoSec Medical Incorporated announced that it has entered into a research collaboration agreement with the University of California, Los Angeles on behalf of Roger S. Lo, M.D., Ph.D. and his research team. [OncoSec Medical Incorporated] Press Release

Alnylam Announces First-Ever FDA Approval of an RNAi Therapeutic, ONPATTRO^™ (Patisiran) for the Treatment of the Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis in Adults

Alnylam Pharmaceuticals, Inc. announced that the FDA approved ONPATTRO^™ lipid complex injection, a first-of-its-kind RNA interference (RNAi) therapeutic, for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. [Alnylam Pharmaceuticals, Inc.] Press Release

Bonti Announces Successful Completion of Phase IIa Scar Reduction Clinical Study

Bonti announced the topline results of its SHINE-1 Phase IIa clinical trial, the first clinical trial in its SHINE (Scar Healing Improvement with Neurotoxin E) clinical program, aimed at scar reduction. [Bonti] Press Release

Investigator-Initiated Phase II Clinical Study of Remetinostat Started in Patients with Basal Cell Carcinoma

Medivir AB announced that the first patient has been enrolled and is being dosed with remetinostat gel 1% in an investigator-initiated Phase II clinical study in patients with basal cell carcinoma. [Medivir AB] Press Release

AVITA Medical Announces Expanded Compassionate Use of RECELL^® Device in Life-Threatening Burns

AVITA Medical announced that the FDA has approved a significant increase in the number of patients who may be treated in the U.S. using the RECELL^® Autologous Cell Harvesting Device under a Compassionate Use Investigational Device Exemption program. [Avita Medical] Press Release

Moleculin Seeks Approval from Polish Regulatory Agency for Skin Cancer Clinical Trial

Moleculin Biotech, Inc. announced it has submitted a request to Polish authorities for clinical trial authorization for its STAT3 inhibitor, WP1220, for the treatment of Cutaneous T-Cell Lymphoma. [Moleculin Biotech LLC] Press Release

US Congress Leaves Science Agencies Hanging — Again

Lawmakers in the US Congress are running out of time to pass a budget for the 2019 fiscal year, and have yet to resolve major disagreements over climate-change and environment programs. [Nature News] Editorial

Gottlieb: FDA Will Streamline Drug Safety Evaluations

The FDA will soon standardize the way it handles data on the safety and effectiveness of drugs in an effort to reduce inconsistencies in the drug review process. [STAT News] Editorial

NEW 19^th Las Vegas Dermatology Seminar
November 1-3, 2018
Las Vegas, Nevada, United States

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

NEW Post-doctoral Positions – Cancer Genetics/Genomics (University of Pennsylvania)

Post-Doctoral Scientist – Novel T Cell Based Cancer Therapies (Netherlands Cancer Institute)

Postdoctoral Fellowship – Epidermal Stem Cell Biology (University of California San Diego School of Medicine)

Postdoctoral Fellowship – Glycobiology of Cancer & Immunology (Brigham & Women’s Hospital, Harvard Medical School)

Associate Professorships – Regenerative Medicine (University of Pavia)

Tenure-Track Faculty Positions – Immunology or Cancer Research (University of Iowa Carver College of Medicine)

Postdoctoral Positions – Gene Regulation and/or Cancer Biology (University of North Carolina at Chapel Hill School of Medicine)

Postdoctoral Research Fellow – Skin Cancer Biology (The University of Colorado)

Associate Professor or Professor – Skin Cancer (The University of Texas M.D. Anderson Cancer Center)

Postdoctoral Researcher – Melanoma (Ghent University)

PhD or Postdoctoral Position – Tissue Repair, Stem Cell Fate and Tumor Heterogeneity (Université Libre de Bruxelles)

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