Dermal Cell News Volume 4.33 | Oct 1 2018

TOP STORY

Epidermal Tissue Adapts to Restrain Progenitors Carrying Clonal p53 Mutations

p53^*/wt progenitors initially outcompeted wild-type cells due to enhanced proliferation, but subsequently reverted toward normal dynamics and homeostasis. Physiological doses of UV light accelerated short-term expansion of p53^*/wt clones, but their frequency decreased with protracted irradiation, possibly due to displacement by UV-induced mutant clones with higher competitive fitness. [Cell Stem Cell] Full Article | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Aging Suppresses Skin-Derived Circulating SDF1 to Promote Full-Thickness Tissue Regeneration

Genetic deletion of stromal-derived factor 1 (SDF1) in young skin enhanced tissue regeneration. In aged mice, enhancer of zeste homolog 2 (EZH2) and histone H3 lysine 27 trimethylation are recruited to the SDF1 promoter at higher levels, and pharmacologic inhibition of EZH2 restores SDF1 induction and prevents tissue regeneration. [Cell Rep] Full Article | Press Release | Graphical Abstract

MicroRNA-203 Modulates Wound Healing and Scar Formation via Suppressing Hes1 Expression in Epidermal Stem Cells

Pre-miR-203 treatment increased epidermal stem cell (ESC) differentiation to myofibroblasts (MFB) cells, as indicated by decreased CK15 ratio and increased MFB biomarkers. This phenomenon was reversed by overexpression of Hes1 in ESCs. In addition, skin incision increased expression of miR-203 in wound tissue. [Cell Physiol Biochem] Full Article

Schizandrin a Alleviates LPS-Induced Injury in Human Keratinocyte Cell HaCaT through a MicroRNA-127-Dependent Regulation

Schizandrin A (SchA) protected HaCaT cells from lipopolysaccharide (LPS)-induced inflammation damage via promoting cell viability, suppressing apoptosis. SchA inhibited IL-1β, IL-6, and TNF-α expression. miR-127 expression was up-regulated in LPS-treated HaCaT cells but down-regulated after SchA treatment. [Cell Physiol Biochem] Full Article

ERK Activating Peptide, AES16-2M Promotes Wound Healing through Accelerating Migration of Keratinocytes

Researchers found that increase in re-epithelialization by AES16-2M early in wound development was due to migration of keratinocytes; a scratch assay using a human keratinocyte cell line also demonstrated effective wound closure by AES16-2M. The migration of keratinocytes effected by AES16-2M was promoted through ERK phosphorylation and blocked with U0126, an ERK inhibitor. [Sci Rep] Full Article

SKIN CANCERS & DISORDERS

LUBAC Prevents Lethal Dermatitis by Inhibiting Cell Death Induced by TNF, TRAIL and CD95L

Scientists demonstrated that keratinocyte-specific deletion of HOIP or HOIL-1 resulted in severe dermatitis causing postnatal lethality. Strikingly, TRAIL or CD95L could redundantly induce this disease-causing cell death, as combined loss of their respective receptors was required to prevent TNFR1-independent dermatitis. [Nat Commun] Full Article

Lysosomal Acid Ceramidase ASAH1 Controls the Transition between Invasive and Proliferative Phenotype in Melanoma Cells

The authors showed that the acid ceramidase ASAH1, which controls sphingolipid metabolism, acted as a rheostat of the phenotypic switch in melanoma cells. Low ASAH1 expression was associated with an invasive behavior mediated by activation of the integrin alphavbeta5-FAK signaling cascade. [Oncogene] Abstract

Staphylococcus aureus from Atopic Dermatitis Skin Accumulates in the Lysosomes of Keratinocytes with Induction of IL-1α Secretion via TLR9

Upon incubation with keratinocytes, three out of four strains of heat killed Staphylococcus aureus from patients with atopic dermititis were strongly agglutinated inside the cytoplasm. In the cells, they were located in lysosomes and promoted the secretion of interleukin-1α (IL-1α). The IL-1α secretion was diminished by the inhibition of Toll-like receptor 9 (TLR9). [Allergy] Abstract

Reprogramming miRNAs Global Expression Orchestrates Development of Drug Resistance in BRAF Mutated Melanoma

Investigators reported that the development of drug resistance to BRAFi was dominated by a dynamic deregulation of a large population of miRNAs, leading to the alteration of cell intrinsic proliferation and survival pathways, as well as of proinflammatory and proangiogenic cues, where a prominent role was played by the miR-199b-5p/VEGF axis. [Cell Death Differ] Full Article

Targeting Lineage-Specific MITF Pathway in Human Melanoma Cell Lines by A-485, the Selective Small Molecule Inhibitor of p300/CBP

Researchers showed that their novel p300/CBP catalytic inhibitor, A-485, induced senescence in multiple melanoma cell lines, similar to silencing expression of EP300 or microphthalmia-associated transcription factor (MITF). A-485 regulated the expression of MITF and its downstream signature genes in melanoma cell lines undergoing senescence. [Mol Cancer Ther] Abstract

Downregulation of miR-145-5p Contributes to Hyperproliferation of Keratinocytes and Skin Inflammation in Psoriasis

Overexpression of miR-145-5p in normal human epidermal keratinocytes (NHEKs) suppressed cell proliferation and secretion of chemokines. In contrast, silencing miR-145-5p promoted NHEK proliferation and increased chemokine secretion. Silencing MLK3 abrogated miR-145-5p inhibitor-induced promotion of cell proliferation and chemokine expression. [Br J Dermatol] Abstract

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Targeting Programmed Cell Death -1 (PD-1) and Ligand (PD-L1): A New Era in Cancer Active Immunotherapy

The authors provide a comprehensive review of the early and late phase trials that led to the regulatory approval of all five PD1- PDL-1 inhibitors in the corresponding cancer types. Current and future challenges in the application of PD-1 and PD-L1 inhibitors are discussed with emphasis on the role of predictive biomarkers. [Pharmacol Ther] Abstract

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

AVITA Medical Announces Presentation of RECELL^® System Effectiveness and Safety

AVITA Medical announced that the results from two U.S. pivotal clinical trials demonstrating the effectiveness and clinical benefits of the RECELL^® Autologous Cell Harvesting Device (RECELL^® System) were presented. [Press release from Avita Medical discussing research presented at the 46^th Annual Eastern Great Lakes Burn Conference, Ann Arbor] Press Release

FDA Approves Libtayo^® (Cemiplimab-Rwlc) as First and Only Treatment for Advanced Cutaneous Squamous Cell Carcinoma

The U.S. FDA has approved Libtayo^® for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. [Sanofi] Press Release

Foamix Announces Additional Positive Topline Results from Third Phase III Trial (Study FX2017-22) Evaluating FMX101 Topical Minocycline Foam for Moderate-to-Severe Acne

Foamix Pharmaceuticals Ltd. announced additional topline results from its third Phase III clinical trial of FMX101 for the treatment of moderate-to-severe acne. The safety profile of FMX101 was consistent with that determined from the two prior Phase III studies. [Foamix Pharmaceuticals Ltd. (GlobeNewswire, Inc.)] Press Release

Targovax Announces Interim Results from Phase I Trial of ONCOS-102 in Checkpoint Inhibitor Refractory Melanoma

The patients received three ONCOS-102 injections prior to KEYTRUDA^® treatment, which may be insufficient in highly advanced disease. As such, Targovax and the investigators now intend to optimize the dosing schedule by increasing the number of ONCOS-102 injections and expand the trial with additional patients. [Targovax] Press Release

The Plastic Surgery Foundation and MTF Biologics Open Applications for Allograft Tissue Research Grant Program

The Plastic Surgery Foundation (PSF) and MTF Biologics are now accepting applications for their Allograft Tissue Research Grant Program. A collaborative effort from The PSF and MTF Biologics that began in 2013, the program funds applied research on biologic reconstruction to enhance patient care. The deadline for submissions is December 3, 2018. [Musculoskeletal Transplant Foundation, dba MTF Biologics] Press Release

Argentina’s Economic Crisis Could Trigger Scientific ‘Collapse,’ Researchers Warn

Argentine scientists are deeply worried about the effects of the country’s economic crisis on science. The government has proposed cutting research budgets in 2019 as part of an austerity push and it is behind in its financial commitments to institutes for this year, which means many labs lack the funds to pay for day-to-day operations. [ScienceInsider] Editorial

Finland Joins Europe’s Bold Open-Access Push

Finland’s national research funder has signed up to Plan S — a push by a group of European organizations to make a radical change to the way that research results are published. [Nature News] Editorial

Biologists Irate at NSF’s New One-Proposal Cap

The National Science Foundation (NSF) in Alexandria, Virginia, has made several tweaks to its grant proposal policies in recent years to keep staff and reviewers from being overwhelmed by the rising number of submissions. But some biologists say the latest change goes too far. [ScienceInsider] Editorial

NEW 4^th International Conference on Nanomedicine, Drug Delivery and Tissue Engineering (NDDTE’19)
April 14-16, 2019
Rome, Italy

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NEW Faculty Positions – Cancer Biology (The Wilmot Cancer Institute at the University of Rochester Medical Center)

Chair – Melanoma Discovery (The University of Western Australia)

Tenure Track Group Leader – Mechanisms in Multicellularity or Tissue Regulation (Friedrich Miescher Institure for Biomedical Research)

Tenure Track Associate Professor – Pathology Department (Biotech Research & Innovation Centre University of Copenhagen)

Group Leader – Organoid Modeling of Disease (European Molecular Laboratory)

Assistant Professor – Department of Biomedical Engineering (Boston University)

Faculty Positions – Cancer Biology (The Wilmot Cancer Institute at the University of Rochester Medical Center)

Associate Researcher – Inflammatory Skin Diseases (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Skin Cancer (Stanford University School of Medicine)

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

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